{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T20:24:14Z","timestamp":1784233454465,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":700,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>A new concept for the inhibition of CGRP signalling has been developed by interaction with the CGRP molecule<jats:italic>per se<\/jats:italic>by using a CGRP antibody or a CGRP binding RNA\u2010Spiegelmer (NOX\u2010C89). We have compared these CGRP scavengers with two known receptor antagonists (CGRP<jats:sub>8\u201337<\/jats:sub>and BIBN4096BS) on CGRP\u2010induced relaxations in the rat middle cerebral artery (MCA). Furthermore, the role of the endothelial barrier has been studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>We used the luminally perfused MCA in an arteriograph, pressurized to 85\u2003mm Hg and myograph studies of isolated ring segments of the MCA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>In myograph studies and in the perfusion system during abluminal application, \u03b1CGRP and \u03b2CGRP induced concentration\u2010dependent dilatation of the MCA. Given luminally neither peptide was significantly vasodilator. Adrenomedullin and amylin induced weak dilatations. In myograph experiments, relaxation induced by \u03b1CGRP was prevented by the four CGRP blockers (CGRP<jats:sub>8\u201337<\/jats:sub>, BIBN4096BS, the CGRP antibody and NOX\u2010C89.). In abluminal perfusion experiments, the relaxant response to \u03b1CGRP was prevented by these agents to a varying degree. Dilatation induced by abluminal application of \u03b1CGRP was inhibited by luminal CGRP<jats:sub>8\u201337<\/jats:sub>but not by luminal BIBN4096BS, CGRP antibody or NOX\u2010C89.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications:<\/jats:title><jats:p>\u03b1 or \u03b2CGRP acted on smooth muscle cell CGRP receptors in rat MCA and were effectively prevented from reaching these receptors by the endothelial barrier. The CGRP blockers significantly inhibited \u03b1CGRP induced relaxation but were also prevented from reaching the CGRP receptors by the arterial endothelium.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2007)<jats:bold>150<\/jats:bold>, 633\u2013640. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707134\">10.1038\/sj.bjp.0707134<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0707134","type":"journal-article","created":{"date-parts":[[2007,1,23]],"date-time":"2007-01-23T16:23:53Z","timestamp":1169569433000},"page":"633-640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Inhibitory effect of BIBN4096BS, CGRP<sub>8\u201337<\/sub>, a CGRP antibody and an RNA\u2010Spiegelmer on CGRP induced vasodilatation in the perfused and non\u2010perfused rat middle cerebral 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