M.Prasad NaiduMSc Medical Biochemistry,Ph.D.Research Scholar

Medulla is the inner part Forms about 20% It is made up of interlacing cords of cells,

which contain fine granules. granules are stained brown by K2Cr2O7 These cells are called chromophil cells or

pheochrom cells or chromaffin cells. Chromaffin cells are of 2 types 1. Adrenaline secreting cells (90%) 2. Noradrenaline secreting cells (10%)

Adrenal medullary hormones are the amines derived from catechol called catecholamines.

3 catecholamines are secreted by medulla

1. Adrenaline or epinephrine (3µg/dl)2. Noradrenaline or norepinephrine

(30)3. Dopamine (3.5µg/dl of plasma)

CCA are syn from Tyr in the chromaffin cells of A.medulla.

Various stages in the syn of CCAs:- 1. Formation of Tyr from Phe in the presence of the

enzyme Phe.hydroxylase 2. Uptake of Tyr from blood into the chromaffin cells of

A.medulla by Active Tpt 3. Convrsion of Tyr into dihydroxyphenylala (DOPA) by

hydroxylation in the presence of Tyrhydroxylase. 4. Decarboxylation of DOPA into dopamine by DOPA

decarboxylase.

5. Entry of dopamine into granules of chromaffin cells.

6. Hydroxylation of dopamine into norEP by the enzyme dopamineβhydroxylase.

7. Release of NEP from granules into the cytoplasm.

8. Methylation of NEP into adrenaline by phenylethenolamine-N-methyltransferase(PNMT

PNMT is present in chromaffin cells.

Half life of CCAs is about 2 minutes. 85% of NEP is taken up by the sympathetic adrenergic

neurons. The biological inactivation (degradation) and removal or

remaining 15% of NEP and adrenal occurs as follows: 1. EP is methylated into meta-adrenaline. NEP is

methoxylated into meta-noradrenalin . The methoxylation occurs in the presence of Catechol-O-Methyltransferase (COMT)

Meta-adrenaline and meta-noradrenaline are together called metanephrines.

2. Then, oxidation of metanephrines into vanilylmandelic acid (VMA) occurs by Monoamineoxidase (MAO)

3. CCAs are removed from body through urine in 3 forms.

i) 50% as free or conjugated meta-adrenaline and meta- noradrenaline

ii) 35% as VMA and iii) 15% as free EP and free NEP

The actions of EP and NEP are excerted through some receptors (adrenergic receptors) present in the target organs.

There are 2 types of receptors called α&β adrenergic receptors.

Receptor Response Mode of axn

α1 More for NEP>EP

Activates phosplolipase C & IP3

Α2 More for NEP>EP

↓adenyl cyclase and cAMP

Β1 Same for both

↑activates the above

β2 EP>NEP same as above

They give more response to NEP > EP

α1 receptors exert their actions by activating the 2nd messenger inositol tri phosphate (IP3) through phospholipase C.

α2 receptors exert their effects by ↓ adenyl cyclase and reducing intracellular cAMP.

β1 receptors have mostly same degree of response to both EP and NEP.

β2 receptors are larger than β1 receptors and show more response to EP than NEP

Both β1 β2 receptors produce their axns by activating adenyl cyclase through G proteins and increasing intracellular cAMP

Effects on metabolism:(via α&β receptors): EP influences the metabolic functions more than NEP.

1.General Metabolism:- i) ↑ O2 consumption and CO2 removal.

It ↑ BMR. It is said to be calorigenic hormone. ii) Carbohydrate metabolism:- EP ↑ blood

glucose level.(↑ glycogenolysis in liver and mus)

iii)fat metabolism:- ↑ lipolysis in AT ( for this function Cortisol need the presence of Cortisol)

Adrenaline ↓ blood clotting time. It ↑ RBC count and Hb content in blood by

causing contraction of spleen and release of RBC into circulation.

Effects on Heart:- EP has stronger effects on heart than NEP.

It ↑ the overall activity of Heart.i.e. ♥ rate (chronotropic effect) , force of contraction (inotropic effect) and excitability of ♥muscle.

NEP causes constriction of blood vessels throughout the body via α- receptors.

NEP is called general Vasoconstrictor.EP also constriction of blood

vessels.However EP causes dialation of blood

vessels in skeletal muscle, liver & heart via β2 receptors.

EP ↑ systolic blood pressure by ↑ the force of contraction and cardiac output.

But it ↓ diastolic pressure by reducing the total peripheral resistance.

NEP ↑ diastolic pressure due to general vasoconstrictor effect by ↑ the total peripheral resistance.

It also ↑ the systolic blood pressure by the actions of heart.

Hypersecretion develops in excessive secretion of catecholamines.

Effects on respiration:-(via β2 recptors) EP ↑ rate & force of respiration. EP also causes bronchodialation. Effects on skin (via α & β2 receptors):- EP ↑ secretion of sweat. Effects on skeletal muscle:- EP causes severe contraction & quick fatigue

of skeletal muscle. It ↑ glycogenolysis and release glu into

blood. It also causes vasodialation in skeletal

muscles.

Effects on Central Nervous system:- EP ↑ the activity of brain. Release of EP ↑ during fight or flight

reactions after exposure to stress. Other physiological functions:- 1.CCAs cause vasoconstriction in salivary

glands leading to mild ↑ in salivary secre 2. CCAs also ↑ the secretary activity of

lacrimal glands. 3. EP ↑ the release of ACTH.

During stress conditions, a large quantity of CCAs is secreted.

During rest, a small quantity of CCAs is secreted.

These hormones prepare the body for fight or flight reactions.

CCAs secretion is also ↑ in conditions like

1. Exposure to cold2. hypoglycemia