Catecholamines
Catecholamines are hormones that are secreted from adrenal medulla portion of adrenal glands. Epinephrine and nor-epinephrine are two major catecholamines present in animals body.
Biosynthesis of catecholamines
Synthesis of catecholamines begins with either of the amino acids phenylalanine or tyrosine. Biosynthetic pathway begins with the conversion of tyrosine to dihydroxy-phenylalanine (DOPA) by tyrosine hydroxylase (TH) which is the rate-limiting enzyme. The products of tyrosine metabolism including DOPA, dopamine, norepinephrine and epinephrine inhibit the activity of TH.
DOPA is then converted to dopamine in the cytosol by the enzyme DOPA decarboxylase. Adrenaline and noradrenaline differ only in the terminal CH3 group.
The conversion of dopamine to norepinephrine occurs within the chromaffin granules by a key enzyme dopamine‑ beta hydroxylase. Norepinephrine moves back into the cytosol where it is converted into epinephrine through the activity of phenylethanolamine‑N‑methyl‑ transferase (PNMT).
Adrenal medulla is the primary source of epinephrine (also present in brain) and nor‑epinephrine is secreted both by medulla and post ganglionic sympathetic neurons.
Epinephrine secreting cells also secrete opioid peptides like met-enkephalins. About 50% of catecholamines are transported bound with albumin and 50% in free form.
The catecholamines are degraded in many tissues but mainly in liver and kidney by the enzymes catechol‑O‑methyl transferase (COMT) and mono-amino oxidase (MAO). The plasma half life of catecholamines is about 2 min.
Mechanisms of action of catecholamines
Catecholamines hormones act in the same way as catecholamine neurotransmitters, i.e. they bind to α- and β-adrenoceptors on the target cell membrane.
Noradrenaline (norepinephrine) is more effective than adrenaline (epinephrine) at α-receptors, while adrenaline (epinephrine) is the more potent agonist at β- receptors. Activation of these receptors modulates the intracellular concentrations of a variety of second messengers, e.g. levels of cAMP may rise or fall.
The pattern of second messenger response actually observed varies from cell to cell and depends on the receptor subtype involved. These intracellular signals alter cell function, often through second messenger-dependent kinases which phosphorylate important functional proteins and so alter their biochemical activities.
Metabolic effects of catecholamines
Metabolic effects of catecholamines is mediated mainly by β2 -receptors. Epinephrine is ten times more potent than norepinephrine in the control of intermediary metabolism.
The effects of epinephrine on glucose metabolism are similar to those of glucagon and opposite to insulin. Epinephrine increases blood glucose level (hyperglycemia) by promoting hepatic glycogenolysis by activating phosphorylase enzyme.
Stimulation of α1 -receptor favours gluconeogenesis. Epinephrine also stimulates glycogenolysis in skeletal muscles resulting inthe production of lactate which is converted into glucose in the liver.
Through a-receptors, epinephrine inhibits insulin secretion and stimulates glucagon secretion, to increase blood glucose concentration.
Epinephrine inhibits insulin effect on adipose tissue, thus promotes lipolysis through β2 -receptors by activation of lipase enzyme and increases free fatty acids concentration in blood
Glucocorticoids potentiate the effect of epinephrine on lipolysis.
Both catecholamines produce arterial vasoconstriction through their a -receptor action. Epinephrine has high affinity for β2 receptors and causes vasodilatation in heart and skeletal muscles and reduces peripheral resistance.
Both epinephrine and norepinephrine interact with β1 -receptors to increase both the force of contraction and heart rate.
The action of epinephrine to increase cardiac output is a beneficial effect in situations as in flight or fight.
Epinephrine increases systolic and decreases diastolic pressure, whereas norepinephrine increases both systolic and diastolic blood pressures.
Epinephrine causes splenic contraction and increases RBC numbers in circulation. Epinephrine produces bronchodilatation by its action on b2 receptor (norepinephrine has little effect) and increases both the rate and depth of respiration.
Epinephrine, through its β-receptor activity, relaxes the intestinal smooth muscles and uterine muscles.
It promotes erection of penis and ejaculation. Norepinephrine causes contraction of uterine smooth muscles.
During cold catecholamines enhances the metabolic rate, non-shivering thermogenesis. Epinephrine constricts renal, splanchnic and cutaneous arterioles, but dilates the arterioles of the muscles to shunt the blood flow particularly to coronary and cerebral blood vessel. By vasoconstriction conserve heat during exposure to cold.
It also improves alveolar gaseous exchange by bronchial dilatation. Epinephrine favors Na+ reabsorption by stimulating renin‑angiotensin-aldosterone mechanism.