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Abstract: The present study was performed to investigate the role of calcitonin gene-related peptide (CGRP) and its receptor in nociception in the basolateral nucleus of amygdala (BLA) of rats. Hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulations were measured by hot plate and Randall Selitto tests. The HWL to both thermal and mechanical stimulations increased significantly after intra-BLA administration of 1.0 or 2.0nmol CGRP, but not 0.5nmol, indicating that CGRP plays an anti-nociceptive role in BLA of rats. The anti-nociceptive effect of 1.0nmol CGRP was blocked significantly by administration of 1.0 or 2.0nmol CGRP8-37, a selective antagonist of CGRP1 receptor, which suggests that the anti-nociceptive effect of CGRP is mediated by the CGRP1 receptor. Taken together, the results indicate that both CGRP and CGRP1 receptor play important roles in nociceptive modulation in the BLA of rats. [Copyright &y& Elsevier]

Background and purpose:A new concept for the inhibition of CGRP signalling has been developed by interaction with the CGRP molecule per se by using a CGRP antibody or a CGRP binding RNA-Spiegelmer (NOX-C89). We have compared these CGRP scavengers with two known receptor antagonists (CGRP8–37 and BIBN4096BS) on CGRP-induced relaxations in the rat middle cerebral artery (MCA). Furthermore, the role of the endothelial barrier has been studied.Experimental approach:We used the luminally perfused MCA in an arteriograph, pressurized to 85 mm Hg and myograph studies of isolated ring segments of the MCA.Key results:In myograph studies and in the perfusion system during abluminal application, αCGRP and βCGRP induced concentration-dependent dilatation of the MCA. Given luminally neither peptide was significantly vasodilator. Adrenomedullin and amylin induced weak dilatations. In myograph experiments, relaxation induced by αCGRP was prevented by the four CGRP blockers (CGRP8–37, BIBN4096BS, the CGRP antibody and NOX-C89.). In abluminal perfusion experiments, the relaxant response to αCGRP was prevented by these agents to a varying degree. Dilatation induced by abluminal application of αCGRP was inhibited by luminal CGRP8–37 but not by luminal BIBN4096BS, CGRP antibody or NOX-C89.Conclusions and Implications:α or βCGRP 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 αCGRP induced relaxation but were also prevented from reaching the CGRP receptors by the arterial endothelium.British Journal of Pharmacology (2007) 150, 633–640. doi:10.1038/sj.bjp.0707134; published online 22 January 2007 [ABSTRACT FROM AUTHOR]

Abstract: The effects of intravenous (iv) adrenomedullin (AM) on gastric emptying were investigated in conscious rats. AM induced a maximal 50% inhibition of gastric emptying at a dose of 1.2nmol/kg. AM was about two-fold less potent than α-calcitonin gene-related peptide (α-CGRP), which induced a similar 50% maximal inhibition of gastric emptying at 0.6nmol/kg. Delayed gastric emptying induced by i.v. AM and α-CGRP was prevented by peripheral injection of the selective CGRP1 antagonist, CGRP8–37, and by pretreatment with indomethacin, while not altered by blockade of the sympathetic nervous system with propranolol. These data indicate that peripheral AM inhibits gastric emptying through the interaction with CGRP8–37-sensitive receptors, likely CGRP1 receptors, and the recruitment of prostaglandin-dependent mechanisms. [Copyright &y& Elsevier]