The Adrenal Glands 2 Adrenal Medulla Introduction The adrenal medulla is the central core of the adrenal gland and its cells chromaffin cells are of neural origin Innervated by preganglionic sympathetic fibers through the splanchnic nerve Acetylcholine is the main stimulus for the release of hormones from the adrenal medulla Adrenomedullary hormones are derived from the amino acid tyrosine Synthesis storage release and transport of adrenal medullary hormones Chromaffin cells synthesize noradrenaline from the precursor dopamine by the catalytic action of an enzyme called dopamine beta hydroxylase Located within synaptic vesicles actively transported into the vesicles Dopamine is produced in the cytoplasm of the nerve terminal from DOPA dihydroxyphenylalanine by the enzyme DOPA decarboyxlase and is then DOPA is produced from tyrosine by the enzyme tyrosine hydroxylase this is the rate limiting step Chromaffin cells also contain the enzyme phenylethanolamine N methyl transferase PNMT which methylates noradrenaline in the cytoplasm to adrenaline Adrenaline is taken up by other vesicles and stored in the nerve terminals Adrenaline and noradrenaline are also called epinephrine and norepinephrine respectively Hormones are secreted by exocytosis of the vesicle contents to the exterior when the cell is stimulated by acetylcholine In humans the main catecholaminergic product from the chromaffin cells is adrenaline 80 of normal output with noradrenaline forming most of the remaining 20 and dopamine being released in minute quantities Chromaffin cells also synthesize and release other molecules in minute amounts such as the enkephalins natural opioids Vesicle contents from the chromaffin cells enter adjacent capillaries and hence reach the bloodstream The adrenal medulla receives arterial blood from the arterial network lying below the capsule Either through the adrenal cortex or cid 127 Mainly from blood which drains between the cords of cells comprising the cortical zones through fenestrated capillaries into venules in the medulla Blood passes through the venules into a central adrenal vein cid 127 Glucocorticoids stimulate tyrosine hydroxylase dopamine beta hydroxylase and PNMT activities thereby exerting a controlling influence on catecholamine synthesis The adrenal medulla is essentially an extension of the sympathetic nervous system cid 127 Once in the circulation the catecholamines have short half lives of less than 3 minutes Rapidly inactivated by uptake into sympathetic nerve terminals or by the enzymes COMT and MAO in the liver kidneys and brain Noradrenaline uptake into the presynaptic sympathetic nerve terminals is by a noradrenaline transporter NAT mechanism called uptake 1 Either recirculated into granules or metabolized by MAO located on the outer surface of the mitochondria Noradrenaline can also be taken up by postsynaptic terminals by a mechanism called uptake 2 Results in breakdown by COMT The final end products of breakdown metanephrins are vanillyl mandolin acid VMA which is mostly excreted in the urine and 3 methyl 4 hydroxy phenylethyleneglycol which is also excreted in the urine but is found conjugated as a glucuronide or sulphate Catecholamine receptors Dopamine is of particular importance as a neurotransmitter in the brain Also has an endocrine role as a hypothalamic inhibitory hormone controlling the release of prolactin from the anterior pituitary Has its own dopamine receptors DR1 and DR2 Adrenaline and noradrenaline exert their effects via adrenergic receptors divided into two groups alpha and beta adrenoceptors All members of the seven transmembrane domain family of receptors All G protein linked receptors In general alpha1 receptors have a greater affinity for noradrenaline and alpha2 receptors have a similar affinity for both Alpha2 receptors are found in the CNS where they inhibit further neurotransmitter release when stimulated For the beta receptors adrenaline generally has a higher binding affinity with beta1 receptors being particularly important regarding control of cardiac smooth muscle and beta2 receptors being involved in mediating many of adrenaline s metabolic effects and the relaxation of bronchiolar smooth muscle Beta3 receptors mediate the effect of adrenaline on BAT in newborns Physiological actions receptor mediated actions cid 127 When the sympathetic nervous system is activated catecholamines mainly adrenaline are released into the general circulation Can then amplify the effects of synaptically released noradrenaline and reach adrenoceptors elsewhere in the body with particular emphasis on beta The overall potentiating effect of circulating catecholamines is of particular importance during the SNS mediated fight or flight response cid 127 Generalized acute response by the body s tissues to a stressor Heart Increased heart rate increased force of contraction Raised arterial blood pressure cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 Vascular smooth muscle Basal tone vasoconstriction Raised arterial blood pressure Lung Brain Eye Relaxation of bronchioles Increased awareness Dilation of pupil Liver muscle adipose tissue Glycolysis lipolysis Raised blood glucose The eccrine and apocrine sweat glands are innervated by postganglionic sympathetic fibers Eccrine sweat is mainly concerned with the loss of latent heat by evaporation of water from the skin surface Apocrine sweat which is much more restricted to certain areas of the body such as the axillae of the arms and the genital region involves the secretion of a normally odorless mucoid secretion which develops a characteristic odor as in comes into contact with bacteria on the skin Stimulation of the SNS is associated with increased sweat production through direct innervations of the sweat glands but only apocrine glands will be stimulated by the circulating catecholamines from the adrenal medullae Control of release The main control over adrenal medullary catecholamine secretion is by the preganglionic sympathetic nerve fibers which innervate the chromaffin cells Any stimulus which results in increased sympathetic activity will induce the release of the adrenomedullary hormones in to the bloodstream Thus emotional or environmental stimuli acting