Antagonistic effect of human α-CGRP [8–37] on the in vivo regional haemodynamic actions of human α-CGRP

A calcitonin gene‐related peptide (CGRP) antagonist (CGRP8–37) inhibits microvascular responses induced by CGRP and capsaicin in skin

“…Both a and 8G forms of CGRP can be released and exert functional effects in man, but CGRP8-37 might have differential inhibitory effects dependent on the form of CGRP released. CGRP8 37 has previously been shown to cause vasoconstriction when infused alone in the rat mesenteric bed in vitro (Han et al, 1990) and in the rat hindquarters in vivo (Gardiner et al, 1990). Results from our experiments show that at a low concentration CGRP8-37 caused a small non-significant decrease in blood flow, possibly as a consequence of inhibiting the actions of basally-released endogenous CGRP.…”

“…This study is confirmed by functional studies which demonstrated that CGRP8 37 is an inhibitor of vascular receptors. CGRP8 37 inhibited vasodilatation of the rat mesenteric arterial bed induced, in vitro, by periarterial nerve stimulation (Han et at., 1990); inhibited CGRP responses of aortic tissue in vitro (Gray et al, 1991) and inhibited the haemodynamic actions of intravenously-injected human aCGRP in the conscious rat (Gardiner et al, 1990). Recent studies indicate that at least two subtypes of CGRP receptors, exist, CGRP1 and CGRP2 and CGRP8 37 is suggested to be a potent antagonist of the CGRP1 receptor (Dennis et al, 1989;.…”

Effects of calcitonin gene‐related peptide receptor antagonists on renal actions of adrenomedullin

“…CGRP(8-37) also inhibited vasodilatation elicited by CGRP in vivo in the rabbit (Hughes & Brain, 1991) and rat (Escott & Brain, 1994) skin beds and in cat cerebral arterioles (Wei et al, 1992). In conscious rats, CGRP(8-37) inhibited vasodilator responses to CGRP in the renal and hindquarter beds and vasoconstrictor response to CGRP in the mesenteric bed (Gardiner et al, 1990;. The ability of CGRP(8-37) to block vascular actions of CGRP but inability to block vasodilator effects of adrenomedullin in the present study suggest that the renal vasodilator effect of adrenomedullin is not mediated via CGRPI receptors.…”

Pharmacological characterization of a receptor for calcitonin gene‐related peptide on rat, L6 myocytes

“…liver (Yamaguchi et al, 1988b), gastric smooth muscle (Maton et al, 1988 The fragment CGRP(8-37) antagonizes the effects of CGRP on rat liver plasma membranes (Chiba et al, 1989), where it appears to have a Kd of about 10nm (although in binding studies it has a Ki of 98 nM), antagonizes the actions of CGRP on the rat mesenteric vascular bed (Han et al, 1989), and antagonizes in vivo haemodynamic effects of CGRP (Han et al, 1989;Gardiner et al, 1990). The related fragment CGRP(12-37) binds with high affinity to brain and spleen membranes, antagonizes the actions of CGRP in the guineapig right atrium but has no effects on the rat vas deferens (Dennis et al, 1989).…”