The role of receptor-operated CA2+ influx in endothelin-induced contraction of the muscularis mucosae

J Cardiovasc Pharmacol. 1998:31 Suppl 1:S504-6. doi: 10.1097/00005344-199800001-00144.

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

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Animals
  • Calcium / metabolism*
  • Endothelin Receptor Antagonists
  • Endothelin-1 / pharmacology
  • Endothelins / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Esophagus / metabolism*
  • Estrenes / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • Pyrrolidinones / pharmacology
  • Receptors, Endothelin / metabolism*
  • Type C Phospholipases / antagonists & inhibitors
  • Vasoconstrictor Agents / pharmacology
  • Viper Venoms / pharmacology

Substances

  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Endothelins
  • Enzyme Inhibitors
  • Estrenes
  • Pyrrolidinones
  • Receptors, Endothelin
  • Vasoconstrictor Agents
  • Viper Venoms
  • sarafotoxins s6
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Type C Phospholipases
  • Calcium