Abstract
We examined the role of receptor-operated Ca2+ influx in endothelin-1 (ET-1)- or sarafotoxin S6c (S6c)-induced contraction of the muscularis mucosae. Responses of the esophageal muscularis mucosae isolated from guinea-pigs were recorded by an isotonic transducer and a polygraph. ET-1 and S6c produced contraction of the esophageal muscularis mucosae in a concentration-dependent manner. The contractile responses to ETs were abolished in a Ca(2+)-free EGTA-containing medium, weakly inhibited by nicardipine, and markedly inhibited by SK&F96365. In addition, both H-7 and U-73122 strongly inhibited the ET-induced contractions, but U-73343 weakly inhibited these responses. These results indicate that the esophageal muscularis mucosae of guinea pigs has ET receptors that are coupled mainly to receptor-operated Ca2+ influx and linked with the phospholipase C-protein kinase C pathway.
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
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Animals
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Calcium / metabolism*
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Endothelin Receptor Antagonists
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Endothelin-1 / pharmacology
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Endothelins / pharmacology*
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Enzyme Inhibitors / pharmacology
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Esophagus / metabolism*
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Estrenes / pharmacology
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Guinea Pigs
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In Vitro Techniques
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Male
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / metabolism*
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Pyrrolidinones / pharmacology
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Receptors, Endothelin / metabolism*
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Type C Phospholipases / antagonists & inhibitors
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Vasoconstrictor Agents / pharmacology
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Viper Venoms / pharmacology
Substances
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Endothelin Receptor Antagonists
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Endothelin-1
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Endothelins
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Enzyme Inhibitors
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Estrenes
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Pyrrolidinones
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Receptors, Endothelin
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Vasoconstrictor Agents
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Viper Venoms
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sarafotoxins s6
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Type C Phospholipases
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Calcium