Specific peptidergic innervation of blood vessels in various organs with particular reference to VIP

1
302 Specific peptidergic innervation of blood vessels in various or- gans with particular reference to VIP. W.G.FORSSMANN and M.REI- NECKE (Institute of Anatomy, University of Heidelberg, FRG). Vasoactive intestinal polypeptide (VIP) has been detected using immunohistochemistry in nerve fibers innervating blood vessels in va- rious organs. These fibers are located in perivascular plexus at the adventitia-media border. However, other neuropeptides such as neuro- tensin (NT), substance P (SP), somatostatin (SOM), angiotensin (ANG), pancreatic polypeptide (PP), enkephalin (ENK) are detected by immuno- cytochemistry in these perivascular plexus. Neuropeptides seem to be in the non-adrenergic and non-cholinergic regulation of cardiovascular function of great importance. We have studied vascular innervation with particular attention to peptidergic nerves. VIP-immunoreactive (IR) varicosities are widely distributed among blood vessels, mainly supplying arteries and arterioles in most viscera. They are located around cerebral, cardiac, pulmonary, gastrointestinal, kidney, and glandular arteries and arterioles. A lesser density of VIP-IR nerves is seen adjacent to veins and venules. In addition to VIP-nerves, other peptides are localized in perivascular plexus. However, they ex- hibit different distribution patterns. For example, kidney blood ves- sels are innervated by a moderate number of SP-IR nerves in the large arterial segments, whereas few SOM-IR and many NT-IR nerves are found. The latter are predominantly located around cortical arteriolar blood vessels. The peptidergic nerves in the perivascular segments in part act vasoconstrictive and in part vasodilative. A few fibers may also be of afferent nature. In summary, the investigation shows that each organ exhibits a specific peptidergic innervation of its supplying blood vessels. This organ specific innervation may be responsible for certain vascular reactions under physiological conditions. Supported by a grant of the German Research Foundation, SFB 90, Carvas. Solid-Phase Synthesis Conformational Studies and Biological Activities of VIP and Related Fragments. FOURNIER~ A., SAUNDERS, J.K. and ST-PIERRE, S. (Department of Physiology and Pharmacology and Department of Chemistry, Uni- versity of Sherbrooke, Sherbrooke, Quebec, Canada JIH 5N4). VIP and related fragments were prepared by the solid-phase method. The synthesis w~s performed on benzhydrylamine resin and the couplings of the Boo-amine acids were carried out by the symmetrical anhydride method. Cleavage was achieved by treatment with liquid HF and purification was accomplished by successive steps of cation exchange, partition and semi-preparative high pressure liquid chromatography. The coumpounds were characterized by thin-layer chromatography, amino acid analysis and analytical hplc. The biological activities of the peptides were evaluated in vitro on the rabbit perfused heart and in vivo on the rat blood pressure. Structur- al studies were performed by high resolution (400 MHz) IH NMR spectroscopy and cir- cular dichroism. Attempts have been made to correlate results of the conformational and biological studies, The results show that among all the fragments tested, only VIP2-28 retains signif- icant biological activity. The fragments devoid of activity were found to be inac- tive as antagonists. VIP and some fragments tend to adopt the helical structure, as demonstrated by spectroscopic techniques.

Transcript of Specific peptidergic innervation of blood vessels in various organs with particular reference to VIP

Page 1: Specific peptidergic innervation of blood vessels in various organs with particular reference to VIP

302

Specific peptidergic innervation of blood vessels in various or- gans with particular reference to VIP. W.G.FORSSMANN and M.REI- NECKE (Institute of Anatomy, University of Heidelberg, FRG).

Vasoactive intestinal polypeptide (VIP) has been detected using immunohistochemistry in nerve fibers innervating blood vessels in va- rious organs. These fibers are located in perivascular plexus at the adventitia-media border. However, other neuropeptides such as neuro- tensin (NT), substance P (SP), somatostatin (SOM), angiotensin (ANG), pancreatic polypeptide (PP), enkephalin (ENK) are detected by immuno- cytochemistry in these perivascular plexus. Neuropeptides seem to be in the non-adrenergic and non-cholinergic regulation of cardiovascular function of great importance. We have studied vascular innervation with particular attention to peptidergic nerves. VIP-immunoreactive (IR) varicosities are widely distributed among blood vessels, mainly supplying arteries and arterioles in most viscera. They are located around cerebral, cardiac, pulmonary, gastrointestinal, kidney, and glandular arteries and arterioles. A lesser density of VIP-IR nerves is seen adjacent to veins and venules. In addition to VIP-nerves, other peptides are localized in perivascular plexus. However, they ex- hibit different distribution patterns. For example, kidney blood ves- sels are innervated by a moderate number of SP-IR nerves in the large arterial segments, whereas few SOM-IR and many NT-IR nerves are found. The latter are predominantly located around cortical arteriolar blood vessels. The peptidergic nerves in the perivascular segments in part act vasoconstrictive and in part vasodilative. A few fibers may also be of afferent nature. In summary, the investigation shows that each organ exhibits a specific peptidergic innervation of its supplying blood vessels. This organ specific innervation may be responsible for certain vascular reactions under physiological conditions.

Supported by a grant of the German Research Foundation, SFB 90, Carvas.

Solid-Phase Synthesis Conformational Studies and Biological Activities of VIP and Related Fragments. FOURNIER~ A., SAUNDERS, J.K. and ST-PIERRE, S. (Department of Physiology and Pharmacology and Department of Chemistry, Uni- versity of Sherbrooke, Sherbrooke, Quebec, Canada JIH 5N4).

VIP and related fragments were prepared by the solid-phase method. The synthesis w~s performed on benzhydrylamine resin and the couplings of the Boo-amine acids were carried out by the symmetrical anhydride method. Cleavage was achieved by treatment with liquid HF and purification was accomplished by successive steps of cation exchange, partition and semi-preparative high pressure liquid chromatography. The coumpounds were characterized by thin-layer chromatography, amino acid analysis and analytical hplc. The biological activities of the peptides were evaluated in v i t r o on the rabbit perfused heart and i n v i v o on the rat blood pressure. Structur- al studies were performed by high resolution (400 MHz) IH NMR spectroscopy and cir- cular dichroism. Attempts have been made to correlate results of the conformational and biological studies,

The results show that among all the fragments tested, only VIP2-28 retains signif- icant biological activity. The fragments devoid of activity were found to be inac- tive as antagonists. VIP and some fragments tend to adopt the helical structure, as demonstrated by spectroscopic techniques.