| Cicletanine-induced decreases in cytosolic Ca2+ level and contraction in vascular smooth muscle. | |
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MedLine Citation:
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PMID: 9517405 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanism by which cicletanine (3-(4-chlorophenyl)-1,3-dihydro-7-hydroxy-6-methylfuro-[3,4-c]pyri dine) induces vasodilatation was examined in isolated vascular smooth muscle. Cicletanine inhibited the contraction induced by high K+, norepinephrine (NE) and prostaglandin F2alpha in a concentration-dependent manner in rat aorta. High K+ (15.8-72.7 mM) elicited elevation of cytosolic Ca2+ level ([Ca2+]i) and contraction in a concentration-dependent manner. Cicletanine (300 microM) inhibited the high K+-induced contractions without changing the [Ca2+]i/tension relationship. NE (3-300 nM) elicited greater contractions than high K+ at a given [Ca2+]i, suggesting that NE increased Ca2+ sensitivity of the contractile elements. Cicletanine inhibited the NE-induced contractions without changing the slope of the [Ca2+]i/tension relationship. Cicletanine inhibited the transient increases in both [Ca2+]i and muscle tension elicited by NE but not the transient increase in [Ca2+]i elicited by caffeine in Ca2+-free solution. Cicletanine did not inhibit contraction induced by Ca2+ in the permeabilized rabbit mesenteric artery with alpha-toxin. These results suggest that cicletanine inhibits vascular smooth muscle contraction by multiple mechanisms: 1) inhibition of Ca2+ influx via voltage-dependent Ca2+ channel and 2) inhibition of Ca2+ release mediated by the alpha-adrenoceptors, but not by caffeine. |
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Authors:
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M Izumi; M Mitsui-Saito; H Ozaki; H Karaki |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Japanese journal of pharmacology Volume: 76 ISSN: 0021-5198 ISO Abbreviation: Jpn. J. Pharmacol. Publication Date: 1998 Jan |
Date Detail:
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Created Date: 1998-05-12 Completed Date: 1998-05-12 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2983305R Medline TA: Jpn J Pharmacol Country: JAPAN |
Other Details:
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Languages: eng Pagination: 57-63 Citation Subset: IM |
Affiliation:
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Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antihypertensive Agents / pharmacology* Aorta, Thoracic / drug effects, metabolism Caffeine / pharmacology Calcium / antagonists & inhibitors, metabolism* Central Nervous System Stimulants / pharmacology Cyclic GMP / analysis Cytosol / drug effects*, metabolism Dinoprost Dose-Response Relationship, Drug Male Muscle Contraction / drug effects Muscle, Smooth, Vascular / drug effects* Norepinephrine Potassium Chloride Pyridines / pharmacology* Rabbits Rats Rats, Wistar Receptors, Adrenergic, alpha / drug effects, metabolism Vasodilation / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Central Nervous System Stimulants; 0/Pyridines; 0/Receptors, Adrenergic, alpha; 51-41-2/Norepinephrine; 551-11-1/Dinoprost; 58-08-2/Caffeine; 7440-70-2/Calcium; 7447-40-7/Potassium Chloride; 7665-99-8/Cyclic GMP; 87520-10-3/cycletanide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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