CALCITONIN-GENE-RELATED PEPTIDE (CGRP)

Calcitonin gene-related peptide (CGRP), a 37 amino acid peptide resulting from the specific maturation processes of calcitonin gene products, was discovered in 1982. Its messenger RNA was isolated from a calcitonin cancer in rats similar to the human thyroid medullary carcinoma. CGRP is closely related to calcitonin and amylin, and to a lesser extent, to the region coding for the alpha chains of relaxins, insulin and insulin growth factors. In thyroid C cells, calcitonin itself is the major gene product, but CGRP is predominant in the central and peripheral nervous system. CGRP is found in most all tissues and is considered to be a neuromediator of particular importance in the cardiovascular system. CGRP is a powerful endogenous vasodilator in man; plasma concentrations of 56 pmol/l (slightly above physiological levels) provoke flush, hypotension and secondary catecholamine release and subsequent tachycardia. Intravenous injections lead to systemic vasodilatation and redistribution of blood flow to the skin, the brain, and probably the splanchnic territory. It has been suggested that CGRP plays a role in blood pressure modulation in certain pathological conditions. CGRP level is decreased in hypertension and increased in septic shock. In patients with terminal renal failure, CGRP is correlated with excess volaemia. It could affect blood pressure by redistributing blood flow, interacting with the renin-angiotensin system or by inhibiting aldosterone secretion. CGRP mag also play a role in modulating cutaneous vascular constriction in Raynaud's syndrome and cerebral vascularization in patients with migraine or meningeal haemorrhage subsequent to rupture of cerebral aneurisms. CGRP increases arterial flow in the cavernous body. Coronarian vascular tone and cardiac performance (positive chronotrope and inotrope effects) are improved. CGRP has also been studied in connection with glucose metabolism and may have other endocrine effects. Finally, CGRP increases electrolyte and water how in the colon and its bronchoconstrictor effect could be implicated in asthma. The clinical significance of plasma CGRP is not yet known although it may be a marker of poor prognosis in thyroid medullary cancer. Recent studies suggest that CGRP could be a useful therapeutic agent in severe Raynaud syndrome, impotency, ischaemic neurological lesions due to ruptured aneurisms and in severe heart failure.