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

3.  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 K 2 Cr 2 O 7  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.  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.  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.  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.  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.  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.  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. ReceptorResponseMode of axn α1α1 More for NEP>EP Activates phosplolipase C & IP3 Α2Α2 More for NEP>EP ↓ adenyl cyclase and cAMP Β1Β1 Same for both ↑ activates the above β2β2 EP>NEP same as above

10.  They give more response to NEP > EP  α 1 receptors exert their actions by activating the 2 nd messenger inositol tri phosphate (IP 3 ) through phospholipase C.  α 2 receptors exert their effects by ↓ adenyl cyclase and reducing intracellular cAMP.

11.  β 1 receptors have mostly same degree of response to both EP and NEP.  β 2 receptors are larger than β 1 receptors and show more response to EP than NEP  Both β 1 β 2 receptors produce their axns by activating adenyl cyclase through G proteins and increasing intracellular cAMP

12.  Effects on metabolism:(via α&β receptors): EP influences the metabolic functions more than NEP.  1.General Metabolism:- i) ↑ O 2 consumption and CO 2 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.  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.  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.  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.  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.  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.  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