Human Alpha-calcitonin Gene-related Peptide Research Articles

Human alpha-calcitonin gene-related peptide (CGRP) is a potent vasodilator in human mesenteric vasculature.

1. The effect of human alpha-calcitonin gene-related peptide (CGRP) and sodium nitroprusside have been measured on human isolated mesenteric vasculature and on rings of human superior mesenteric artery and saphenous vein. 2. When noradrenaline (10(-5) M) was used as the vasoconstrictor in preparations perfused with Krebs solution at constant flow, human alpha-CGRP was 10 times more potent than sodium nitroprusside in evoking dose-dependent falls in perfusion pressure. 3. Human alpha-CGRP and sodium nitroprusside were about equipotent at relaxing rings of superior mesenteric artery contracted by noradrenaline (10(-6) M). When the tone of saphenous vein rings was raised by noradrenaline (10(-6) M), human alpha-CGRP did not relax the vascular smooth muscle. 4. The results show that human alpha-CGRP is a potent vasodilator in human arterial preparations and may act preferentially on arterioles rather than large arteries.

A COMPARISON OF THE DISTRIBUTION OF SUBSTANCE P AND CALCITONIN GENE‐RELATED PEPTIDE RECEPTORS IN THE RAT BLADDER

Binding of [125I]Bolton-Hunter labelled substance P (BH-SP) and [125I]human alpha-calcitonin gene-related peptide (h alpha CGRP) to rat bladder tissue sections was characterized and the respective binding sites localized by light-microscopic autoradiography. BH-SP binding sites were localized to epithelium, blood vessels and smooth muscle while hCGRP binding sites were present only over the epithelium. These results suggest that the range of biological actions of substance P and calcitonin gene-related peptide, which may be co-released from the same afferent terminals, might be determined by the different distributions of their respective receptors.

Actions of calcitonin gene-related peptide and tachykinins in relation to the contractile effects of capsaicin in the guinea-pig and rat heart in vitro.

1. The effects of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide K (NPK) and substance P (SP) on contractility of the guinea-pig and rat heart were studied in vitro in relation to the response to capsaicin. 2. Human (h) CGRP alpha (alpha) and beta (beta) were equipotent in stimulating the contractile force and rate of the spontaneously beating guinea-pig right atrium. 3. Both NKA and NPK inhibited contractile force and rate in the guinea-pig atrium whilst a mainly negative chronotropic effect was observed in the whole heart. SP did not influence cardiac contractility. 4. Human CGRP alpha and beta mimicked the contractile effects of capsaicin in the guinea-pig atrium. In the whole heart preparation, hCGRP alpha and capsaicin increased heart rate whereas capsaicin also evoked an atropine-resistant inhibition of contractile force. The stimulatory effect of capsaicin on heart rate was absent after systemic capsaicin pretreatment, while the inhibition of ventricular contractile tension remained unchanged. 5. Extended incubation with hCGRP alpha or beta was associated with development of cross-tachyphylaxis between these two agents in the guinea-pig atrium. However, CGRP tachyphylaxis did not change the atrial response to noradrenaline, forskolin or NKA. The stimulatory effects of capsaicin on atrial contractility were absent after tachyphylaxis to hCGRP alpha or beta. 6. There was no detectable supersensitivity to the stimulatory effects of rat (r) CGRP alpha on the spontaneously beating atrium after capsaicin pretreatment of adult or neonatal rats. In conclusion the present data provide further evidence that the capsaicin-induced stimulation of atrial contractility is due to local release of CGRP.(ABSTRACT TRUNCATED AT 250 WORDS)