Crítica!Review

Cephalic Reflexes: Their Role in Digestion and PossibleRoles in Absorption and Metabolism

SHARON A. GIDÃœCK,ROSE M. THREATTE ANDMORLEY R. KARE

Mondi Chemical Senses Center, Philadelphia, PA 19104

ABSTRACT Stimulation of the oral cavity immediately elicits salivation, gastric acid secretion and pancreatic exocrine andendocrine secretions that serve to prepare the alimentary canal for digestion, transport and utilization of ingested nutrients.Oropharyngeal-stimulated responses are reliably initiated by the taste and smell of food. These gastrointestinal reflexes, oftenreferred to as anticipatory or cephalic phase responses, are mediated by the autonomie nervous system and are believed to beindependent of the postabsorptive effects of ingested nutrients. A common pathway used by cephalic phase responses to triggergastrointestinal secretions is the vagus. Several studies have also demonstrated that cephalic stimulation activates both thesympathetic and parasympathetic nervous systems and thus, many cephalic-metabolic reflexes may arise indirectly from moregeneral physiological changes that accompany oropharyngeal stimulation. The present studies suggest that oral stimulationresults in alterations in intestinal function. Specifically, oropharyngeal stimulation of conscious, unrestrained rats with sucroseincreases the uptake of radioactive glucose from the small intestine into the hepatic portal blood. J. Nutr. 117: 1191-1196,1987.

INDEXING KEY WORDS:

•cephalic reflexes •oropharyngeal stimulation •digestion •absorption •chemosensory •taste

The role of taste and smell in food selection and inmotivating an organism to consume a meal is obvious.Not as widely recognized is the impact on gastrointestinal secretory function by the chemical senses andother oropharyngeal stimuli. Pavlov (1)was the first todocument quantitatively that sensory and mechanicalinput at the level of the oropharyngeal cavity can re-flexively stimulate secretions at several locations alongthe gastrointestinal tract. These gut reflexes, which areactivated by the stimulation of receptors located in thehead and neck, are collectively known as cephalic phaseresponses (1-3). Powley (4) has defined cephalic responses of digestion as "autonomie and endocrine reflexes involved in the metabolism of food that are triggered by sensory contact with foodstuffs rather than bypostingestional consequences of food." Nicolaidis (2)suggested that these cephalic responses play an important role in the regulation of both digestive and metabolic processes and act to optimize the utilization ofthe ingested nutrients.

Cephalic responses can arise from the taste, smell ormerely the sight and sound of food (1-3, 5, 6-9). Stimulation of receptors, including chemoreceptors and me-chanoreceptors (activated by chewing and swallowing),

can initiate the gut responses. Once cephalic components have been activated, the gut anticipatory response is mediated by the vagus nerve, which can bereflexively stimulated either by the central nervous system or by visceral efferents (5, 10). An intact vagus isnecessary for these gastrointestinal anticipatory reflexes to occur (11-14). Powley (4) has suggested thatcephalic responses have three defining traits: a] afferentlimbs that originate in the head and neck region; b]integration and relay pathways within the central nervous system; and c) efferent limbs consisting of neuraland neuroendocrine pathways that control gastrointestinal function.

Classically, the cephalic phase is contrasted with thegastric and intestinal phases of digestion; the latter twophases are related to the postingestional consequencesof food, whereas the former is associated with thepreabsorptive consequences of food. The responses triggered by the cephalic phase are anticipatory in the sensethat they are in the same direction as those that occurduring the gastric and intestinal phases (13, 15-19).However, they are more rapid in onset, of shorter duration and usually lower in magnitude than secretionsstimulated during the gastric and intestinal phases.

0022-3166/87 $3.00 ©1987 American Institute of Nutrition. Received 7 April 1986. Accepted 26 February 1987.

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Nevertheless, cephalic phase events appear to influencethe magnitude of subsequent postingestional gastrointestinal responses (1, 2, 5, 6, 13, 15-20).

Although the existence of cephalic-gut reflexes hasbeen repeatedly demonstrated, the physiological significance of these responses remains undefined. A major function that these cephalic responses probably serveis to "prime" the gut and modulate metabolic processes

so that optimal digestion, absorption and utilization ofthe ingested nutrients occur (2-5). This is supportedby reports in which rats denied oropharyngeal stimulation by means of intragastric (21, 22) or intravenousfeeding (2)generally had lower body weight gains thanthose fed orally at similar energy intakes. Moreover,cephalic phase responses may function to modulate theinflux of the ingested nutrients as suggested by Nico-laidis (2) so that large deviations in absorption and utilization of the nutrient do not occur. For example, whenthe cephalic release of insulin is prevented by intragastric feeding (18, 23) or pharmacological vagotomy(24), the resulting hyperglycemia is much greater inmagnitude than that which results from oral feeding.

The role of taste and smell thus extends beyond itsobvious involvement in food selection to the modulation of digestive function. The following discussionwill focus upon the interrelationship between cephaliccomponents and gastrointestinal function. The effectsof oropharyngeal stimulation on digestive (i.e., gastricand pancreatic secretions) and metabolic reflexes willbe emphasized in a review of recent work. The discussion of metabolic reflexes will focus on physiologicalchanges that directly and/or indirectly affect digestion.Finally, new data will be presented to support the concept of a cephalic-intestinal absorption reflex.

CEPHALIC-GASTROINTESTINAL SECRETORYREFLEXES

Salivary secretion. Saliva is the first secretion to bedirectly stimulated by the presence of food in the mouth(25). In addition to lubricating foods for swallowing,saliva contains the enzymes amylase and lipase, whichinitiate the digestion of starch and fats. The classicstudies of Pavlov (1) with dogs included a demonstration that salivary output increased upon the presentation of food. Visual and olfactory stimulation can alsoincrease saliva output in animals (26) and humans (27)but not to the extent that occurs when food is tastedor chewed. When human subjects chewed on plastictubing for 30 min salivary flow approximately doubled,indicating that the mechanical act of chewing alonecan also stimulate flow (27).

Alterations in salivary flow may be influenced moreby the physical and chemical nature of foods than bythe palatability. For example, strong acids such as lemonjuice are potent stimuli for salivation and produce asaliva rich in protein (25). Interestingly, when saliva

output was measured in humans in response to onlythe sight of various foods, the highest saliva outputoccurred in response to foods that contain irritants suchas acids or spices that provide potent stimulation wheningested (28).This suggests that prior learning may alsobe important in influencing the cephalic phase of salivary secretion.

Gastric secretions. The secretion of pepsinogen andhydrochloric acid from the fundic glands and the secretion of gastrin from the neuroendocrine glands inthe antrum of the stomach occur in response to cephalic stimulation and are mediated by the vagus nerve(11, 12, 29). Moreover, vagai stimulation arising fromcephalic events potentiates the responsiveness of theparietal cell to gastrin (11).The cephalic phase of gastricsecretion was first documented by Pavlov (1)using thetechnique of sham feeding. This technique eliminatesthe gastric and intestinal phases of digestive secretionsby diverting the ingested food directly to the exteriorvia an esophageal fistula (1). When dogs with esopha-geal fistulas and Pavlov pouches (innervated) were shamfed, acid and pepsinogen were secreted from both themain body of the stomach and the pouch. However, ifthe vagi were cut, then sham feeding no longer resultedin secretion. Pavlov inferred from his studies that themagnitude of the gastric response to sham feeding wasdependent on the palatability of the food (1).Similarly,in human subjects, it has been demonstrated that themagnitude of gastric acid secretion during the cephalicphase is directly related to the acceptability of the meal(30-33). Feldman and Richardson (33)recently reportedthat olfactory stimulation by food is relatively poor ateliciting gastric secretions as compared to taste or sightof food.

Pancreatic secretions. A cephalic phase of pancreaticexocrine secretion has been reported in many species(14, 34-39). However, its importance has been questioned because it is difficult to separate the stimulatoryeffects of hormones such as gastrin and secretin fromdirect cephalic effects. Preshaw, Cooke and Grossman(37)reported that when gastrin secretion was inhibitedby acidification of the Pavlov pouch in the dog, theincrease in pancreatic exocrine secretion upon shamfeeding was reduced. However, damage to vagai fibersinnervating the pancreas may have occurred during surgical preparation of the pouch in these studies. Novis,Banks and Marks (38) later authenticated a cephalicphase of pancreatic exocrine secretion in humans withachlorohydria; chewing and masticating followed byexpectoration of the food resulted in a pancreatic juicerich in chymotrypsinogen, trypsinogen and lipase without an effect on the volume or bicarbonate levels. Ithas been demonstrated that electrical stimulation ofthe vagus nerve rather than sham feeding also resultsin moderate increases in pancreatic enzyme secretionin the cat (40) and dog (41) and a copious secretion ofwater, bicarbonate and amylase in the pig even afterremoval of the stomach and intestines (42).

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As with gastric secretion, the nature of the taste stimulus influences the magnitude of the pancreatic response. Behrman and Kare (43), using conscious dogsequipped with gastric and duodenal fistulas, observedthat water or sucrose mixed with a basal diet producedhigher pancreatic flow rates and protein outputs thandid citric acid- or quinine-adulterated diets. Furthermore, Nairn, Kare and Merritt (34)quantitated this withrespect to time and reported that palatable sucrose solutions and nonpurified diets (commercial dog food)also produced greater pancreatic exocrine secretions thanpurified diets or a cellulose-water mix.

In addition to pancreatic exocrine secretions, activation of cephalic receptors leads to preabsorptivechanges in pancreatic endocrine secretions. Animalssham fed various solutions such as glucose and tapwater exhibit immediate increases in insulin secretionthat are produced without any change in blood glucoseconcentration (23; see also 7, 13, 44). Furthermore, ithas been demonstrated that oropharyngeal-induced insulin secretion can be inhibited by vagotomy (1,13).Taste solutions given intragastrically (2)or given aftersuperficial anesthesia of the oral mucosa (IO) do notalter blood insulin levels, indicating that the preabsorptive secretion of insulin is dependent on orophar-yngeal stimulation.

It has also been demonstrated that the sight, smelland taste of food can elicit pancreatic glucagon release(45). This response is inhibited by atropine and thus,is probably mediated by cholingeric neural pathways.A cephalic phase of pancreatic polypeptide release thatis vagally mediated has also been demonstrated (46,47).Deglutition appears to augment the release of pancreatic polypeptide (48).

The palatability of taste stimuli is important in theoropharyngeal stimulation of pancreatic endocrine secretion. For example, when rats are fed diets containingsaccharin, the magnitude of the preabsorptive insulinresponse observed is greater than when the animals arefed an unflavored diet (49),whereas the addition of quinine resulted in insulin levels lower than those of eitherthe saccharin or unflavored diets. Berthoud et al. (44)reported similar results when rats ingested a smallamount (1mL) of saccharin and quinine solutions, demonstrating that a direct neural link between oropharyngeal sensory input and the pancreas is involved.

CEPHALIC-METABOLIC REFLEXES

The effects that chemosensory and other cephalicstimuli have on the systemic physiology of an organismhave received relatively little attention since Pavlov's

research. Numerous investigations performed on human subjects and other animals have demonstrated thatcephalic stimulation activates both the sympatheticand parasympathetic nervous systems (50-53). As a

result, many of the anticipatory metabolic reflexes thathave been documented may be secondary to the directeffects of cephalic phase vagai and sympathetic nervoussystem activation. However, this does not detract fromthe possible physiological significance of these events.For example, the increase in respiratory quotient inresponse to eating (2)and the hyperglycémieresponsesto oropharyngeal stimulation with sweet-tasting substances in hungry rats (2) are two metabolic reflexesthat are probably a secondary result of the activationof the parasympathetic and sympathetic nervous systems. Recent neuroanatomical studies are beginning toprovide new insight into the neural pathways betweenchemosensory and autonomie systems. This area is beyond the scope of this paper and the reader is referredto Norgren (54).

Postprandial thermogenesis, which is the normal increase in heat production that occurs after food is ingested, also is probably a secondary cephalic response.In recent studies by LeBlanc, Cabanac and Samson (53)in which human subjects were allowed to consumefood orally, heat production increased threefold within15 min after eating. However, when the food was givenby gastric gavage to circumvent sensory inputs, theearly increase in postprandial thermogenesis was fourtimes smaller. Although this technique cannot directlyassess the contribution of cephalic stimulation, otherstudies with dogs have shown that sham feeding produces an increase in heat production that is quantitatively similar to the one that occurs in the first 40 minafter the oral ingestion of food (55).Interestingly enough,the smell and even the sight of food were also sufficientto initiate a cephalic phase of heat production that wassimilar in magnitude to that produced by sham feeding(55). The initial increase in heat production observedin these studies during ingestion is too rapid to be theresult of the absorption of the ingested nutrients andcannot be accounted for by the processes of ingestion.Because early thermogenesis is paralleled by increasesin both norepinephrine and insulin, it has been hypothesized that the cephalic phase of thermogenesismay be related to the levels of catecholamines (53, 55).In support of this idea, when human subjects ingestedfoods that were unpalatable or when the oropharyngealcavity was bypassed by gastric gavage, sympathetic activation as measured by both catecholamine levels andpostprandial thermogenesis was suppressed (52, 53).

Recent studies have demonstrated that the cardiovascular system also responds to feeding in essentiallytwo phases (56-58). During anticipation and the initialingestion of food, there is a transient increase in cardiacoutput, aortic blood pressure and heart rate accompanied by either an increase or no change in mesentericvascular resistance (57, 58). Within 5-30 min afterfeeding, cardiac output, heart rate and blood pressurereturn to normal while blood flow through the superiormesenteric artery begins to rise and continues to do sofor 30-90 min. These responses can be attenuated by

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administration of sympathetic blocking agents (56).Thus, as in the case of early postprandial thermogen-esis, the secretion of catecholamines may play an important role in the cardiovascular changes that occurduring this ingestion phase.

CEPHALIC-INTESTINAL ABSORPTION REFLEX

Studies have not been conducted to investigate thepossibility that changes in the intestinal function arereflexively stimulated by taste and smell and activationof cephalic receptors. It seems possible that an increasein the capacity of the intestine to transport nutrientsmay serve in a feed-forward action to prepare the intestine for the efficient absorption and transport of incoming nutrients.

Preliminary studies conducted in our laboratory havesupported the hypothesis that oropharyngeal stimulation with a sweet taste results in an increase in theabsorption of glucose from the small intestine of conscious, unrestrained rats. By infusing a glucose solution(containing [14C-U]glucose)directly into the intestineand estimating the uptake of glucose (by sampling hepatic portal blood and determining the rate of appearance of glucose) before and after oral stimulation, itwas demonstrated that both 0.3 M sucrose and water,when given orally (100 jxL),result in an increase in theappearance of glucose in the hepatic portal blood. Fromthese studies, the area under the curve of time versusnM glucose/mL blood was estimated (59) during thefirst 10 min immediately following presentation of theoral stimuli (Table 1). From these data, the mean S:Wwas 2.90 ±0.27 (n = 4) indicating that the increase inglucose in the hepatic portal blood that resulted fromthe intraoral delivery of sucrose was three times greaterthan that following the intraoral delivery of water, whichindicated some specificity of the induced response.Studies are currently in progress to confirm these preliminary findings.

As with many cephalic-metabolic responses, a changein intestinal transport of nutrients may not be a primary response, but may be secondary to other reflexes

TABLE 1

Estimation of appearance ol glucose in thehepatic portal blood after oral stimulation with

either water or surcóse as the taste stimulus

Area under curve(nMglucose •min)

ml blood

Rat Water Sucrose

10918653

145

392558138347

3.603.002.602.39

'Sucrose-to-water ratio of areas resulting from oral stimulation.

elicited along the gut and/or in response to vagai andsympathetic activation produced by oropharyngeal sensory and mechanical input. The vagus has been shownto mediate many of the cephalic phase responses asdescribed previously and may be involved in mediatingcephalic-induced changes in intestinal function. However, although the vagus has a demonstrable effect onthe motor and secretory functions of the gastrointestinal tract, direct control of intestinal absorption hasbeen difficult to demonstrate (50, 59-61). On the otherhand, sympathetic stimulation appears to increase theabsorption of fluid and electrolytes (50, 62, 63).

As discussed above, the sympathetic nervous systemis believed to play a significant role in the cardiovascular changes that occur in the anticipation and ingestion of food (56-58). Alterations in blood flow to theabsorptive site concomitant with changes in gut mo-tility can also influence the net absorption of nutrientssuch as amino acids and electrolytes (64, 65). Whine(65), reviewing numerous studies, observed a positivecorrelation between blood flow and the absorption ofpassively and actively transported substances. Increased blood flow can increase absorption by increasing O2 delivery to the mucosa, altering tissue colloidosmotic pressure or increasing the removal of an absorbed nutrient, thus increasing the concentration gradient between the lumen and the blood (65). Correlations between motility, blood flow and absorption wereobserved by Pytkowski and Michalowski (66): The absorption of amino acids from the jejunum was directlyproportional to blood flow and inversely proportionalto gut motility.

Changes in intestinal absorption may also occur secondarily to the release of gastrointestinal hormones whosesecretion is stimulated by the anticipation and presenceof food in the oropharyngeal cavity (61,64, 67).Sarr, Kellyand Phillips (61)observed a postprandial increase in theabsorption of glucose, water, sodium and chloride froman isolated, extrinsic denervated canine jejunal segment. Because the effect occurred in the absence ofextrinsic innervation, they suggested that the hormones secreted in response to a meal may, in part,affect intestinal function. These hormones may directly affect enterocyte functions, or alter intestinalblood flow or motility (61, 65, 67-69). For example,glucagon has been shown to increase intestinal bloodflow (70). Other peptides, such as substance P and vas-oactive intestinal peptide, may act locally to alter enterocyte function, possibly through cAMP, as shown inthe rat (71).Vasoactive intestinal peptide receptors arepresent on the basolateral membranes of enterocytesof rat jenunum (71).

CONCLUSIONS

The chemical senses may influence the nutritionalstatus of an organism by affecting digestion and met-

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abolie processes at several levels. This review focusedon a) well-known gastrointestinal secretory responsesto oropharyngeal stimulation, b] metabolic processesthat are stimulated by parasympathetic (especially vagai) and sympathetic activation that are induced byoropharyngeal sensory and mechanical inputs and c)changes in intestinal absorption that could result fromoropharyngeal stimulation. These cephalic-induced responses probably function to "prime" the gut physiologically for the meal and thus, play an influential rolein the nutritional status of an organism.

ACKNOWLEDGMENT

We thank Joseph G. Brand for reading and reviewingthis manuscript.

LITERATURE CITED

1. PAVLOV,I. P. (1910) Work of the Digestive Glands (translatedby W. H. Thompson), 2nd ed., Charles Griffin, London.

2. NICOLAIDIS,S. (1969) Early systemic responses to orogastricstimulation in the regulation of food and water balance: functional and electrophysiological data. Ann. N.Y. Acad. Sci. 157:1176-1200.

3. BRAND,J. G., CAGAN,R. H. & NAIM,M. (1982) Chemical senses in the release of gastric and pancreatic secretions. Annu. Rev.Nutr. 2: 249-276.

4. POWLEY,T. L. (1977) The ventromedial hypothalamic syndrome, satiety, and a cephalic phase hypothesis. Psychol. Rev.84: 89-126.

5. BRAND,J. G., NAIM, M. & KARE,M. R. (1981) Taste and nutrition. In: Handbook of Nutritional Requirements in a Functional Context (Rechcigl, M., éd.),pp. 255-282, CRC Press, BocaRaton.

6. GRILL,H. J. & NORGREN,R. (1978) The taste reactivity test: I.Mimetic response to gustatory stimuli in neurologically normalrats. Brain Res. 143: 263-279.

7. BERRIDGE,K., GRILL,H. J. & NORGREN,R. (1981) Relation ofconsummatory responses and preabsorptive insulin release topalatability and learned taste aversions. /. Comp. Physio!. Psychol. 95: 363-382.

8. FISCHER,U., HOMMEL,H., ZIEGLER,M. & IUTZI,J. (1972) Themechanism of insulin secretion after oral administration. Ill:Investigations on the mechanism of a reflectoric insulin mobilization after oral stimulation. Diabetologia 8: 385-390.

9. FISCHER,U, HOMMEL,H., ZIEGLER,M. & MICHAEL,R. (1972) Themechanism of insulin secretion after oral administration I. Mul-tiphasic course of insulin mobilization after oral administrationof glucose in conscious dogs. Differences in the behavior afterintravenous administration. Diabetologia 8: 104-110.

10. BROOKS,F. P. (1977) Nervous control of gastrointestinal function: Neurophysiological considerations. In: Progress in Gastro-enterology, III (Glass, G. B. I., éd.),pp. 373-393, GruñeandStratton, New York.

11. BONFILS,S., MIGNON,M. & ROZE,C. (1979) Vagai control ofgastric secretion. In: International Review of Physiology; Gastrointestinal Physiology HI (Crane, R. K., éd.),pp. 59-106, University Park Press, Baltimore.

12. KONTUREK, S. ]., KWIECIEN, N., OBTULOWICZ, W., MlKOS, E.,

SITO, E., OLEKSY,J. & POPIELA,T. (1978) Cephalic phase of

gastric secretion in healthy subjects and duodenal ulcer patients:role of vagai innervation. Gut 20: 875-881.

13. LOUIS-SYLVESTRE,J. (1976) Preabsorptive insulin release andhypoglycemia in rats. Am. ]. Physiol. 230: 56-60.

14. SOLOMON,T. & GROSSMAN,M. I. (1977) Vagai control of pancreatic exocrine secretion. In: Nerves and the Gut (Brooks, F. P.&. Evers, P. W., eds.), pp. 119-129, C. B. Slack, Thorofare, NI.

15. MOORE,J. G. & MOTORI,D. (1979) Gastric secretory and humoral responses to anticipated feeding in five men. Gastroen-terology 76: 71-75.

16. MOORE,J. G. & SCHENKENBERG,T. (1974) Psychic control ofgastric acid: response to anticipated feeding and biofeedbacktraining in a man. Gastroenterology 66: 954-959.

17. NILSSON,G. & UVNAS-WALLENSTEN,K. (1975) Effect of teasing,sham feeding and feeding on plasma insulin concentrations indog. Hormone and metabolic research In: Radioimmunoassay:Methodology and Applications in Physiology and in ClinicalStudies (Luft, B. & Yalow, B., eds.), pp. 91-97, PSG Publications,Littleton, MA.

18. STEFFENS,A. B. (1976) Influence of the oral cavity on insulinrelease in the rat. Am. f. Physiol. 230: 1411-1415.

19. STRUBBE,J. H. & STEFFENS,A. B. (1975) Rapid insulin releaseafter ingestion of a meal in the unanesthetized rat. Am. f. Physiol.229: 1019-1022.

20. ELRICK,H., STIMMLER,L., HLAD,G. f. & ARAI,Y. (1964) Plasmainsulin response to oral and intravenous glucose administration./. Clin. Endocrino! Metal. 24: 1076-1082.

21. YOUNG,E. A., QOLETTI,L. A., WINBORN,W. B., TRAYLOR,J. B.,BALDARAS,L. & WESER,E. (1980) Comparative study of nutritional adapation to defined formula diets in rats. Am. ]. Clin.Nutr. 33: 2106-2108.

22. YOUNG,E. A., CIOLETTI,L. A., TRAYLOR,J. B. & BALDERAS,V.(1982) Gastrointestinal response to oral versus gastric feedingof defined formula diets. Am. /. Clin. Nutr. 35: 715-726.

23. HOMMEL,H., FISCHER,U, RETZLAFF,L. & KNOFLER,H. (1972) Themechanism of insulin secretion in conscious dogs bearing fistulasof the digestive tract by sham-feeding of glucose or tap water.Diabetologia 8: 111-116.

24. LOUIS-SYLVESTRE,f. (1978) Relationship between two stages ofprandial insulin release in rats. Am. ¡.Physiol. 4: E103-E111.

25. DAVENPORT,H. W. (1982) Physiology of the Digestive Tract,5th ed., Year Book Medical Publishers, Chicago.

26. ELSBERG,C. A., SPOTNITZ,H. & STRANGIN,E. I. (1940) Theeffects of stimulation by odorous substances upon the amountof secretion by parotid glands. /. Exp. Psychol. 27: 58.

27. RICHARDSON,C. T. & FELDMAN,M. (1986) Salivary responseto food in humans and its effect on gastric acid secretion. Am./. Physiol. 250: G85-G91.

28. CHRISTENSEN,C. & NAVAZECH,M. (1984) Anticipatory salivary flow to the sight of different foods. Appetite 5: 307-315.

29. GROSSMAN,M. I. (1967) Neutral and hormonal stimulation ofgastric secretion of acid. In: Handbook of Physiology (Code, C.F., ed.), Sect. 6, vol. 2, pp. 835-863, American Physiological

Society, Washington, DC.30. IANOWITZ,H. D., HOLLANDER,F., ORRINGER,D., LEVY,M. H., WIN-

KELSTEIN,A., KARUFMAN,M. R. & MARGOLIN,S. G. (1950) Aquantitative study of the gastric secretory response to sham feedings in a human subject. Gastroenterology 16: 104-116.

31. MALAGELADA,f.-R., Go, V. L. W. & SUMMERSKILL,W. H. J.(1979) Different gastric, pancreatic and biliary responses to solid-liquid or homogenized meals. Dig. Dis. Sci. 24: 101-110.

32. PARKER,f. G., WERTHER,J. L. & HOLLANDER,F. (1963) Gastriccation secretion in a patient with complete esophageal obstruction and permanent gastrotomy. Am. f. Dig. Dis. 8: 319-329.

33. FELDMAN,M. &. RICHARDSON,C. T. (1986) The cephalic phaseof gastric secretion. In: Interaction of the Chemical Senses withNutrition (Kare, M. R. & Brand, J. B., eds.), pp. 181-192, Academic, Orlando.

34. NAIM,M.,KARE,M.R. & MERRITT,A.M. (1978) Effectsoforal

by guest on June 14, 2014jn.nutrition.org

Dow

nloaded from

1196 GIDUCK, THREATTE AND KARE

stimulation on the cephalic phase of pancreatic exocrine secretion in dogs. PhysioL Behav. 20: 563-570.

35. KONTUREK,S. J. (1977) Gastric secretion. In: GastrointestinalPhysiology (Jacobson, E. D. & Shanbaur, L. L., eds.|, pp. 227-264, University Park Press, Baltimore.

36. NAIM, M. & KARE,M. R. (1977] Taste stimuli and pancreaticfunctions. In: The Chemical Senses and Nutrition (Kare, M. R.& Maller, O., eds.), pp. 145-163, Academic, New York.

37. PRESHAW,R. M., COOKE,A. R. & GROSSMAN,M. I. (1966) Shamfeeding and pancreatic secretion in the dog. Gastroenterology 50:171-178.

38. Novis, B. H., BANKS,S. & MARKS,I. N. (1971) The cephalicphase of pancreatic secretion in man. Scand. ¡.Gastroenterol. 6:417-421.

39. SARLES,H., DANI, R., PREZELIN,G., SOUVILLE,C. & FIGARELLA,C.(1968) Cephalic phase of pancreatic secretion in man. Gut 9:214-221.

40. UVNAS-WALLENSTEN,K. & NILSSON,G. (1978) A quantitative

study of insulin release induced by vagai stimulation in anesthetized cats. Acta PhysioL Scand. 102: 137-142.

41. KAMINSKI,D. L, RUWART,M. I. & WILLMAN,V. L. (1975) Theeffect of electrical vagai stimulation on canine pancreatic exocrine function. Surgery 77: 545-550.

42. MACEE,D. F. & WHITE,T. T. (1965) Influence of vagai stimulation on secretion of pancreatic juice in pigs. Ann. Surg. 161:605-607.

43. BEHRMAN,H. R. & KARE,M. R. (1968) Canine pancreatic secretion in response to acceptable and aversive taste stimuli. Proc.Soc. Exp. Biol. Med. 129: 343-346.

44. BERTHOUD,H. R., TRIMBLE,E. R., SIEGEL,E. G., BEREITER,D. A. &JEANRENAUD,B. (1980) Cephalic phase insulin secretion innormal and pancreatic islet-transplanted rats. Am. J. PhysioL238: E336-E340.

45. DENCKER,H., HEDNER,P., HOLST,J. &. TRANBERG,K. G. (1975)Pancreatic glucagon response to an ordinary meal. Scand. ]. Gastroenterol. 10: 471-474.

46. ADRIAN,T. E., BESTERMAN,H. S., COOKE,T. J. C., BLOOM,S. R.,BARNES,A. ]., RÃœSSEL,R. C. G. & FARBER,R. G. (1977) Mechanisms of pancreatic polypeptide release in man. Lancet 1: 161-163.

47. SCHWARTZ,T. W., HOLST,J. J., FAHRENKRUG,J., JENSEN,S. L., NIEL-SON,O. V., REHFELD,J. F., SCHAFFALITZKYDEMUCKADELL,O. B. &STADIL,F. (1978) Vagai, cholinergic regulation of pancreaticpolypeptide secretion. /. Clin. Invest. 61: 781-789.

48. SCHWARTZ,T. W., STENQUIST,B. & OLBE,L. (1979) Cephalicphase of pancreatic polypeptide secretion studied by sham feeding in man. Scand. /. Gastroenterol. 14: 313-320.

49. LOUIS-SYLVESTRE,J. & LEMAGNEN,J. (1980) Palatability andpreabsorptive insulin release. Neurosa. Biobehav. Rev. 4: 43-46.

50. WRIGHT,R. D., JENNINGS,M. A., FLOREY,H. W. & LIUM, R.(1940) The influence of nerves and drugs on secretion by thesmall intestine and an investigation of enzymes in intestinaljuice. Q. /. Exp. PhysioL 30: 73-120.

51. GROSSMAN,M. I. (1979) Neural and hormonal regulation ofgastrointestinal function: an overview. Annu. Rev. PhysioL 41:27-33.

52. WELLE,S. L., LILAVTVATHANA,V. & CAMPBELL,R. G. (1980)Increased plasma norepinephrine concentrations and metabolic

rates following glucose ingestion in man. Metabolism 29: 806-809.

53. LEBLANC,J., CABANAC,M. & SAMSON,P. (1984) Reduced postprandial heat production with gavage as compared with mealfeeding in human subjects. Am. /. PhysioL 246: E95-E101.

54. NORGREN,R. (1985) Taste and the autonomie nervous system.Chem. Senses 10: 143-161.

55. DIAMOND,P., BRONDEL,L. & LEBLAC,J. (1985) Palatability andpostprandial thermogenesis in dogs. Am. f. PhysioL 248: E75-E79.

56. FRONEK,K. & STAHLGREN,L. H. (1968) Systemic and regionalhemodynamic changes during food intake and digestion in non-anesthetized dogs. Circ. Res. 23: 687-692.

57. VATNER,S. F., FRANKLIN,D. & VANCITTERS,R. L. (1970) Mes-enteric vasoactivity associated with eating and digestion in theconscious dog. Am. f. PhysioL 219: 170-174.

58. VATNER,S. F., PATRICK,T. A., HIGGINS,C. B. & FRANKLIN,D.(1974) Regional circulatory adjustments to eating and digestionin conscious unrestrained primates. /. Appi. PhysioL 36: 524-529.

59. ZIERLER,K. L. (1958) A simplified explanation of the theoryof indicator-dilution for measurement of fluid flow and volume

and other distributive phenomena. Bull, ¡ohnsHopkins Hasp.103: 199-217.

60. BUNCH,G. A. & SHIELDS,R. (1973) The effects of vagotomyon the intestinal handling of water and electrolytes. Gut 14: 116-119.

61. SARR,M. G., KELLY,K. A. & PHILLIPS,S. F. (1982) Feeding augments canine jejunal absorption via a hormonal mechanism. Dig.Dis. Sci. 26: 961-965.

62. HUBEL,K. A. (1976) Intestinal ion transport: effect of norepinephrine, pilocarpine and atropine. Am /. PhysioL 231: 252-257.

63. SIOVALL,H. (1984) Sympathetic control of jejunal fluid andelectrolyte transport. Acta PhysioL Scand. 535: 1-52.

64. CHOU,C. C., MONGINO,M. J. & SAWMTLLER,D. R. (1984) Gastrointestinal hormones and intestinal blood flow. In: Physiologyof Intestinal Circulation (Shepherd, A. P. & Granger, D. N., eds.),pp. 121-130, Raven, New York.

65. WINNE,G. I. (1979) Influence of blood flow on intestinal absorption of drugs and nutrients. /. Pharmacol. Exp. Ther. 6: 333-393.

66. PYTKOWSKI,B. & MICHALOWSKI,J. (1977) Motility and bloodflow dependent absorption of amino acids in canine small intestine. Em. /. Clin. Invest. 7: 79-86.

67. POITRAS,P., MODIGLIANI,R. & BERNIER,J. J. (1980) Effect of acombination of gastrin, secretin, choleystokinin, glucagon andgastric inhibitory polypeptide on jejunal absorption in man. Gut21: 299-304.

68. HICKS,T. & TURNBERG,L. A. (1973) The influence of secretinon ion transport in the human jejunum. Gut 14: 485-490.

69. FREEDMAN,J., RASMUSSEN,H. & DOBBINS,f. W. (1980) So-

matostatin stimulates coupled sodium chloride influx across brushborder of the rabbit ileum. Biochem. Biophys. Res. Commun.97: 243-247.

70. BOWEN,J. C., PAWLIK,W. W., FANG, W. F. & JACOBSON,E. D.(1975) Pharmacological effects of gastrointestinal hormones onintestinal O2 consumption and blood flow. Surgery 78: 515-519.

71. HUBEL,K. A. (1985) Intestinal nerves and ion transport: stimuli, reflexes and responses. Am. ]. PhysioL 248: 6261-6271.

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