Interaction of amylin with calcitonin gene‐related peptide receptors in the microvasculature of the hamster cheek pouch in vivo

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 . 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 βCGRP (10.8±0.3), human αCGRP (10.8±0.4), rat αCGRP (10.4±0.3). Rat amylin and the CGRP 2 receptor selective agonist [Cys(ACM 2,7 ]‐human αCGRP were 100 fold less potent (estimates were 8.5±0.4 and 8.2±0.3 respectively). The GCRP 1 receptor antagonist, CGRP 8–37 (300 nmol kg −1 ; i.v.) reversibly inhibited the increase in diameter evoked by human αCGRP (0.3 n M ) from 178±22% to 59±12% ( n =8; P <0.05) and by rat amylin (100 n M ) from 138±23% to 68±24% ( n =6; P <0.05). CGRP 8–37 did not inhibit vasodilation evoked by substance P (10 n M ; n =4; P >0.05). The amylin receptor antagonist, amylin 8–37 (300 nmol kg −1 ; i.v.) did not significantly inhibit the increase in diameter evoked by human αCGRP (0.3 n M ) 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 n M ) which was 146±23% in the absence and 144±32% in the presence of antagonist ( n =4; P >0.05). 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 CGRP 1 receptors in the hamster cheek pouch.British Journal of Pharmacology (1999) 126 , 280–284; doi: 10.1038/sj.bjp.0702272