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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Tam, C. W. Lazar, Z. Brain, S. D. Grant, A. D. Shih, M. K. |
| Description | Author Affiliation: Grant AD ( Centre for Cardiovascular Biology & Medicine, New Hunt's House, King's College London, Guy's Campus, London SE1 1UL, U.K.) |
| Abstract | Calcitonin gene-related peptide (CGRP) is a potent microvascular dilator neuropeptide that is considered to play an essential role in neurogenic vasodilatation and in maintaining functional integrity in peripheral tissues. We have examined the effect of the nonpeptide CGRP antagonist BIBN4096BS on responses to CGRP and the structurally related peptide adrenomedullin, AM, in murine isolated aorta and mesentery preparations, and in the cutaneous microvasculature in vivo. We show for the first time that BIBN4096BS is an effective antagonist of CGRP and AM responses in the murine mesenteric and cutaneous microvasculature, and of CGRP in the murine aorta. After local administration, BIBN4096BS selectively inhibits the potentiation of microvascular permeability in the cutaneous microvasculature by CGRP and AM, with no effect on responses induced by other microvascular vasodilators. BIBN4096BS reversed both newly developed and established vasoactive responses induced by CGRP. The ability of CGRP to potentiate plasma extravasation was lost when coinjected with compound 48/80 (where mast cells would be activated to release proteases), but regained when soybean trypsin inhibitor was coinjected with compound 48/80. These results demonstrate that BIBN4096BS is a selective antagonist of responses induced by CGRP and AM in the mouse microvasculature, and CGRP in the mouse aorta. The ability of BIBN4096BS to block an established CGRP microvascular vasodilatation indicates that the sustained vasodilator activity of CGRP is due to the retention of the active intact peptide and the continued involvement of the CGRP receptor. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 7 |
| Volume Number | 142 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2004-08-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Microcirculation Drug Effects Peptides Antagonists & Inhibitors Piperazines Pharmacology Quinazolines Receptors, Calcitonin Gene-Related Peptide Vasodilation Physiology Adrenomedullin Animals Aorta In Vitro Techniques Mesenteric Arteries Mice Metabolism Skin Blood Supply Trypsin Inhibitors P-Methoxy-N-methylphenethylamine Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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