Calcitonin Gene-Related Peptide Mediated Neurogenic Vasorelaxation in the Isolated Canine Lingual Artery
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概要
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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<SUP>-6</SUP> M) to block neurogenic constrictor responses. In the presence of norepinephrine (10<SUP>-5</SUP> 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<SUP>-5</SUP> M), and atropine (10<SUP>-5</SUP> M) did not affect the relaxation elicited by electrical stimulation in endothelium-intact rings. <I>N</I><SUP>G</SUP>-monomethyl-L-arginine (10<SUP>-4</SUP> M) or <I>N</I><SUP>G</SUP>-nitro-<SUB>L</SUB>-arginine methyl ester (10<SUP>-4</SUP> 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<SUP>-8</SUP> M), a CGRP<SUB>1</SUB>-receptor antagonist, inhibited neurogenic relaxation of endothelium-denuded rings; substance P (10<SUP>-6</SUP> M) failed to mimic the observed effect of electrical stimulation. The demonstrated effect of electrical stimulation was inhibited by glibenclamide (10<SUP>-5</SUP> M), but not tetraethylammonium (2×10<SUP>-4</SUP> M); glibenclamide abolished the relaxation in response to exogenous CGRP or the ATP-sensitive K<SUP>+</SUP> channel opener cromakalim (10<SUP>-6</SUP> M) in endothelium-denuded rings. Moreover, tetrodotoxin (3.13×10<SUP>-6</SUP> 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<SUP>-6</SUP> 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 CGRP<SUB>1</SUB> receptors.
- 社団法人 日本薬理学会の論文
- 1995-04-01
著者
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OKABE Eiichiro
Department of Pharmacology and ESR Laboratory, Kanagawa Dental College
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Okabe Eiichiro
Department Of Pharmacology
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Okabe Eiichiro
Deparment Of Pharmacology Kanagawa Dental College
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Kobayashi Dai
Department Of Computer Science Graduate School Of Information Science And Engineering Tokyo Institut
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Kobayashi Dai
Department Of Pharmacology
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TODOKI Kazuo
Department of Pharmacology
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OZONO Satoru
Pathology, Kanagawa Dental College
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Ozono Satoru
Pathology Kanagawa Dental College
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