The role of receptor-operated CA2+ influx in endothelin-induced contraction of the muscularis mucosae.
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.
Uchida
K
K
Department of Pharmacology, Dokkyo University School of Medicine, Tochigi, Japan.
Yuzuki
R
R
Kamikawa
Y
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004947:Esophagus / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D010738:Type C Phospholipases; D002118:Calcium