Volume 126, Issue 1, Page 280

British Journal of Pharmacology

January 1999, Volume 126, Issue 1, Pages 280 - 284

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Original Article

Interaction of amylin with calcitonin gene-related peptide receptors in the microvasculature of the hamster cheek pouch in vivo
Judith M. Hall^1,3 & Susan D. Brain²
¹Pharmacology Group, School of Biological Sciences, University of Surrey, Guildford, Surrey, GU2 5XH     ²Pharmacology Group and Vascular Biology Research Centre, Biomedical Sciences Division, King's College London, SW3 6LX

³Author for correspondence

Keywords

CGRP;   amylin;   CGRP_{8 - 37};   microvasculature;   amylin_{8 - 37};   sensory nerves;   blood flow;   amylin antagonist;   CGRP antagonist;   vasodilation

Abstract

1   This study used intravital microscopy to investigate the receptors stimulated by amylin which shares around 50% sequence homology with the vasodilator calcitonin gene-related peptide (CGRP) in the hamster cheek pouch microvasculature in vivo.
2   Receptor agonists dilated arterioles (diameters 20 - 40 µm). The -log of the concentrations (±s.e.mean; n=8) causing 50% increase in arteriole diameter were: human beta CGRP (10.8±0.3), human alpha CGRP (10.8±0.4), rat alpha CGRP (10.4±0.3). Rat amylin and the CGRP₂ receptor selective agonist [Cys(ACM^2,7]-human alpha CGRP were 100 fold less potent (estimates were 8.5±0.4 and 8.2±0.3 respectively).
3   The GCRP₁ receptor antagonist, CGRP_{8 - 37} (300 nmol kg^-1; i.v.) reversibly inhibited the increase in diameter evoked by human alpha CGRP (0.3 nM) from 178±22% to 59±12% (n=8; P<0.05) and by rat amylin (100 nM) from 138±23% to 68±24% (n=6; P<0.05). CGRP_{8 - 37} did not inhibit vasodilation evoked by substance P (10 nM; n=4; P>0.05).
4   The amylin receptor antagonist, amylin_{8 - 37} (300 nmol kg^-1; i.v.) did not significantly inhibit the increase in diameter evoked by human alpha CGRP (0.3 nM) which was 112±26% in the absence, and 90±29% in the presence of antagonist (n=4; P<0.05); nor that evoked by rat amylin (100 nM) which was 146±23% in the absence and 144±32% in the presence of antagonist (n=4; P>0.05).
5   The agonist profile for vasodilatation and the inhibition of this dilatation by CGRP_{8 - 37}, although not the amylin_{8 - 37} indicates that amylin causes vasodilatation through interaction with CGRP₁ receptors in the hamster cheek pouch.

Received 26 June 1998; Revised 25 September 1998; Accepted 6 October 1998