Study of Cgrp-Receptors in Human Isolated Middle Meningeal Arteries Using Bibn4096Bs, Compound 1, and HαCgrp(8-37)

Z Razzaque,M Bock,J Pickard,L Maskell,J Longmore,D Sirinathsinghji,D Shaw

doi:10.1100/tsw.2001.437

Abstract

Calcitonin, CGRP, adrenomedullin, and amylin require both CRLR (calcitonin-gene receptor like receptor) and receptor activity modifying proteins (RAMP1, RAMP2, and RAMP3) in different combinations for expression of selective, functional receptors[1]. We investigated whether the antagonists BIBN4096BS[2], Compound 1 (WO98/11128, [3]), and CGRP(8-37) are functionally selective for CGRP receptors in human middle meningeal arteries (HMMA).

Highlights

Calcitonin, CGRP, adrenomedullin, and amylin require both CRLR and receptor activity modifying proteins (RAMP1, RAMP2, and RAMP3) in different combinations for expression of selective, functional receptors[1]
Responses to adrenomedullin were unaltered by BIBN4096BS (10 nM)
It is predicted that if CGRP mediated neurogenic vasodilation contributes to migraine pathophysiology CGRP antagonists may have clinical utility

Summary

Introduction

Calcitonin, CGRP, adrenomedullin, and amylin require both CRLR (calcitonin-gene receptor like receptor) and receptor activity modifying proteins (RAMP1, RAMP2, and RAMP3) in different combinations for expression of selective, functional receptors[1]. METHODS Isometric tension recordings were made (in presence of 10 μM thiorphan) in isolated segments of HMMA (obtained with consent).

Results

Conclusion