ADRENAL MEDULLA

1. M.Prasad Naidu MSc Medical Biochemistry, Ph.D.Research Scholar ADRENAL MEDULLACatecholamines

3. Introduction • 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%)

4. Hormones of adrenal medulla • 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)

5. Synthesis of catecholamines • 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.

6. Synthesis of catecholamines • 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.

7. Metabolism of catecholamines • 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.

8. Metabolism of catecholamines • 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

9. Mode of axn of EP & NEP-adrenergic receptors • 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.

10. Alpha adrenergic receptors • 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.

11. beta adrenergic receptors • 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 β1β2 receptors produce their axns by activating adenyl cyclase through G proteins and increasing intracellular cAMP

12. Actions of EP & NEP • 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)

13. Effects on blood (via β receptors) • 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.

14. Effects on Blood vessels • 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.

15. Effects on blood pressure (via α &β 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.

16. Other functions • 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.

17. Other functions • 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.

18. Regulation of secretion of EP & NEP • 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 cold • 2. hypoglycemia