BIBN4096BS is a potent competitive antagonist of the relaxant effects of α-CGRP on human temporal artery: comparison with CGRP(8-37)

Authors


  • See also DOI: 10.1038/sj.bjp.0704669

  • inline imageThe 3D images show T2 lesions (yellow), ventricles (blue), caudate (pink) and putamen (green) with brain surface (gray, transparent). The 2D axial slice additionallly includes white matter (red) and csf (cyan). MRI scans were acquired through the Conte Center for depression in the elderly (Krishnan, Duke and James Macfall at Duke). The images were processed by Dr Guido Gerig at UNC. The lesions are commonly seen in elderly subjects and is related to depression in late life and to dementia.

Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG. E-mail: ajk41@hermes.cam.ac.uk

Abstract

  • Release of CGRP during migraine may produce harmful dilatation of cranial arteries, thereby possibly causing pain. We have compared the antagonism by BIBN4096BS and CGRP(8-37) of the relaxant effects of α-CGRP on rings of human temporal artery.

  • α-CGRP relaxed the arteries precontracted with 9 – 24 mM KCl (−logEC50=9.4) nearly as efficaciously as sodium nitroprusside (10 μM).

  • BIBN4096BS (0.1 – 100 nM) antagonized the effects of α-CGRP in surmountable manner with slopes of Schild-plots not different from unity. −LogKB values of 10.1 and 10.4 were estimated for BIBN4096BS when administered before or during the KCl-contracture respectively.

  • BIBN4096BS (1 μM) did not modify the relaxant effects of papaverine and sodium nitroprusside.

  • CGRP(8-37) (1 – 10 μM) antagonized the effects of α-CGRP in a surmountable manner with slopes of Schild-plots not different from unity. −LogKB values of 6.6 and 6.7 were estimated for CGRP(8-37) administered before or during the KCl-contracture respectively.

  • The high affinity of BIBN4096BS for CGRP receptors of human temporal artery makes it an excellent tool to explore the hypothesis of CGRP-evoked cerebral vasodilation in migraine.

British Journal of Pharmacology (2002) 136, 120–126; doi:10.1038/sj.bjp.0704682

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