20% of the mass of adrenal gland. It is made up of interlacing cords of cells known as chromaffin cells. Chromaffin cells are also called pheochrome cells or chromophil cells. These cells contain fine granules which are stained brown by potassium dichromate. Types of chromaffin cells Adrenal medulla is formed by two types of chromaffin cells: 1. Adrenaline-secreting cells (90%) 2. Noradrenaline-secreting cells (10%). „ HORMONES OF ADRENAL MEDULLA Adrenal medullary hormones are the amines derived from catechol and so these hormones are called catecholamines. Catecholamines secreted by adrenal medulla 1. Adrenaline or epinephrine 2. Noradrenaline or norepinephrine 3. Dopamine. „ PLASMA LEVEL OF CATECHOLAMINES 1. Adrenaline : 3 μg/dL 2. Noradrenaline : 30 μg/dL 3. Dopamine : 3.5 μg/dL „ HALF-LIFE OF CATECHOLAMINES Half-life of catecholamines is about 2 minutes. „ SYNTHESIS OF CATECHOLAMINES Catecholamines are synthesized from the amino acid tyrosine in the chromaffin cells of adrenal medulla (Fig. 71.1). These hormones are formed from phenylalanine also. But phenylalanine has to be converted into tyrosine. Stages of Synthesis of Catecholamines 1. Formation of tyrosine from phenylalanine in the presence of enzyme phenylalanine hydroxylase 2. Uptake of tyrosine from blood into the chromaffin cells of adrenal medulla by active transport 3. Conversion of tyrosine into dihydroxyphenylalanine (DOPA) by hydroxylation in the presence of tyrosine hydroxylase 440 Section 6tEndocrinology FIGURE 71.1: Synthesis of catecholamines. DOPA = Di- hydroxyphenylalanine, PNMT = Phenylethanolamine-N- methyltransferase. 4. Decarboxylation of DOPA into dopamine by DOPA decarboxylase 5. Entry of dopamine into granules of chromaffin cells 6. Hydroxylation of dopamine into noradrenaline by the enzyme dopamine beta-hydroxylase 7. Release of noradrenaline from granules into the cytoplasm 8. Methylation of noradrenaline into adrenaline by the most important enzyme called phenylethanolamine- N-methyltransferase (PNMT). PNMT is present in chromaffin cells. „ METABOLISM OF CATECHOLAMINES Eighty five percent of noradrenaline is taken up by the sympathetic adrenergic neurons. Remaining 15% of noradrenaline and adrenaline are degraded (Fig. 71.2). FIGURE 71.2: Metabolism of catecholamines. COMT = Catechol-O-methyltransferase, MAO = Monoamine oxidase. Stages of Metabolism of Catecholamines 1. Methoxylation of adrenaline into meta-adrenaline and noradrenaline into metanoradrenaline in the presence of ‘catechol-O-methyltransferase’ (COMT). Meta-adrenaline and meta-noradrenaline are together called metanephrines 2. Oxidation of metanephrines into vanillylmandelic acid (VMA) by monoamine oxidase (MAO) Removal of Catecholamines Catecholamines are removed from body through urine in three forms: i. 15% as free adrenaline and free noradrenaline ii. 50% as free or conjugated meta-adrenaline and meta-noradrenaline iii. 35% as vanillylmandelic acid (VMA). „ ACTIONS OF ADRENALINE AND NORADRENALINE Adrenaline and noradrenaline stimulate the nervous system. Adrenaline has significant effects on metabolic functions and both adrenaline and noradrenaline have significant effects on cardiovascular system. „ MODE OF ACTION OF ADRENALINE AND NORADRENALINE – ADRENERGIC RECEPTORS Actions of adrenaline and noradrenaline are executed by binding with receptors called adrenergic receptors, which are present in the target organs. Chapter 71tAdrenal Medulla 441 Adrenergic receptors are of two types: 1. Alpha-adrenergic receptors, which are subdivided into alpha-1 and alpha-2 receptors 2. Beta-adrenergic receptors, which are subdivided into beta-1 and beta-2 receptors. Refer Table 71.1 for the mode of action of these receptors. „ ACTIONS Circulating adrenaline and noradrenaline have similar effect of sympathetic stimulation. But, the effect of adrenal hormones is prolonged 10 times more than that of sympathetic stimulation. It is because of the slow inactivation, slow degradation and slow removal of these hormones. Effects of adrenaline and noradrenaline on various target organs depend upon the type of receptors present in the cells of the organs. Adrenaline acts through both alpha and beta receptors equally. Noradrenaline acts mainly through alpha receptors and occasionally through beta receptors. 1. On Metabolism (via Alpha and Beta Receptors) Adrenaline influences the metabolic functions more than noradrenaline. i. General metabolism: Adrenaline increases oxygen consumption and carbon dioxide removal. It increases basal metabolic rate. So, it is said to be a calorigenic hormone ii. Carbohydrate metabolism: Adrenaline increases the blood glucose level by increasing the glycogenolysis in liver and muscle. So, a large quantity of glucose enters the circulation iii. Fat metabolism: Adrenaline causes mobilization of free fatty acids from adipose tissues. Catecholamines need the presence of glucocorticoids for this action. 2. On Blood (via Beta Receptors) Adrenaline decreases blood coagulation time. It increases RBC count in blood by contracting smooth muscless