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

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 mm). The 7log of the concentrations (+s.e.mean; n=8) causing 50% increase in arteriole diameter were: human bCGRP (10.8+0.3), human aCGRP (10.8+0.4), rat aCGRP (10.4+0.3). Rat amylin and the CGRP 2 receptor selective agonist [Cys(ACM 2,7 ]-human aCGRP were 100 fold less potent (estimates were 8.5+0.4 and 8.2+0.3 respectively). 3 The GCRP 1 receptor antagonist, CGRP 8 ± 37 (300 nmol kg 71 ; i.v.) reversibly inhibited the increase in diameter evoked by human aCGRP (0.3 nM) from 178+22% to 59+12% (n=8; P50.05) and by rat amylin (100 nM) from 138+23% to 68+24% (n=6; P50.05). CGRP 8 ± 37 did not inhibit vasodilation evoked by substance P (10 nM; n=4; P40.05). 4 The amylin receptor antagonist, amylin 8 ± 37 (300 nmol kg 71 ; i.v.) did not signi®cantly inhibit the increase in diameter evoked by human aCGRP (0.3 nM) which was 112+26% in the absence, and 90+29% in the presence of antagonist (n=4; P50.05); 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; P40.05). 5 The agonist pro®le 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.

Characterization of adenosine receptors mediating the vasodilator effects of adenosine receptor agonists in the microvasculature of the hamster cheek pouch in vivo

“…As NECA was the most potent agonist, the response to this agonist in the presence of adenosine receptor antagonists was studied. Repeated control curves to NECA showed that there was no loss of response with time or after repeated administration (results not shown), as shown previously for adenosine and other vasodilators (Jackson, 1993, Hall & Brain, 1994, 1999). None of the antagonists altered the resting diameter of the blood vessels (Fig.…”

“…As in other studies (e.g. Jackson, 1993, Hall & Brain, 1994, 1999), no time‐dependent changes in sensitivity to the agonists was noted.…”

“…The arterioles were observed with a Zeiss Axioskop microscope having a 20× salt‐water dipping objective and 10× eye pieces. Blood vessels were visualized using a Zeiss CCD video camera system and the external diameters of blood vessels were measured after magnification on screen, manually (Hall & Brain, 1999).…”

Central and peripheral cardiovascular actions of adrenomedullin 5, a novel member of the calcitonin gene-related peptide family, in mammals

“…All CGRP family peptides exhibit cardiovascular actions, although relative potency differs among the members, CGRPOAMRAM2[amylin (Ando et al 1990, Charles et al 1997, Hall & Brain 1999, Fujisawa et al 2004. CGRP is a neuropeptide in the brain and periphery, which is released from axon terminals innervating the vascular smooth muscles (see Brain & Grant 2004 for review).…”

An unwell child with a florid rash

“…Amylin has been shown to have both vasodilator 20 and anti-inflammatory 21 properties. It shares 50% homology with calcitonin gene related peptide, which is recognised to be raised in acute inflammatory states such as trauma, 8 sepsis (neonatal and adult), 9 and hypotensive shock.…”