Calcitonin Gene-Related Peptide Mediated Neurogenic Vasorelaxation in the Isolated Canine Lingual Artery

The Japanese Journal of Pharmacology

Kazuo Todoki¹  Satoru Ozono²  Dai Kobayashi¹  Eiichiro Okabe¹ 

[1] Departments of Pharmacology, Kanagawa Dental College;Departments of Pathology, Kanagawa Dental College

关键词: Lingual artery;    Calcitonin gene-related peptide;    Glibenclamide;    Adenosine 5' triphosphate-sensitive potassium channel;    Non-adrenergic non-cholinergic nerve;   

DOI  :  10.1254/jjp.67.329

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(35)Cited-By(5)The nature of neurogenic relaxation was investigated in ring preparations of canine lingual artery. In all experiments, the preparations were previously treated with guanethidine (5 × 10-6 M) to block neurogenic constrictor responses. In the presence of norepinephrine (10-5 M) to induce tone, electrical stimulation (10 V, 4 to 16 Hz, for 45 sec) produced relaxation of the rings in an endothelium-independent fashion. The relaxant response in endothelium-denuded rings was not changed by propranolol (10-5 M), and atropine (10-5 M) did not affect the relaxation elicited by electrical stimulation in endothelium-intact rings. NG-monomethyl-L-arginine (10-4 M) or NG-nitro-L-arginine methyl ester (10-4 M), a nitric oxide (NO) synthase inhibitor, had no effect on the electrical stimulation-induced relaxation of endotheliumdenuded rings. Human calcitonin gene-related peptide (CGRP)-(8 - 37) (2×10-8 M), a CGRP1-receptor antagonist, inhibited neurogenic relaxation of endothelium-denuded rings; substance P (10-6 M) failed to mimic the observed effect of electrical stimulation. The demonstrated effect of electrical stimulation was inhibited by glibenclamide (10-5 M), but not tetraethylammonium (2×10-4 M); glibenclamide abolished the relaxation in response to exogenous CGRP or the ATP-sensitive K+ channel opener cromakalim (10-6 M) in endothelium-denuded rings. Moreover, tetrodotoxin (3.13×10-6 M) inhibited the relaxation of endotheliumdenuded rings induced by electrical stimulation. The relaxation was selectively inhibited when endogenous CGRP had been depleted from perivascular nerves by capsaicin (10-6 M). These results suggest that CGRP, but not NO, released from non-adrenergic non-cholinergic nerves by electrical stimulation produces relaxation of canine lingual artery that is mediated by activation of CGRP1 receptors.

【 授权许可】

Unknown