A pertussis toxin‐sensitive mechanism of endothelin action in porcine coronary artery smooth muscle

Y. Kasuya, Y. Takuwa, Masashi Yanagisawa, T. Masaki, K. Goto

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Endothelin‐1 (ET‐1)‐induced contraction of porcine coronary artery strips may be mediated via at least two intracellular signalling mechanisims, the activation of dihydropyridine‐sensitive voltage‐dependent Ca2+ channels and the stimulation of phosphoinositide breakdown. Here we have investigated the possible involvement of pertussis toxin (PT)‐sensitive guanosine‐5′‐triphosphate (GTP)‐binding proteins (G‐proteins) in ET‐1‐induced activation of these two signalling pathways in porcine coronary artery smooth muscle. Increase in extracellular K+ concentration (10, 15 mm) shifted the dose‐response relationship for the ET‐1‐induced contraction to the left. The dihydropyridine Ca2+ channel blocker, nifedipine (10−8 m), induced a rightward shift in the dose‐response curve for ET‐1. Pretreatment of the arterial strips with PT (0.1 μg ml−1) induced a similar rightward shift of the ET‐1 dose‐response curve but not of the KCl response. Nifedipine (10−8 m) did not further attenuate the ET‐1‐induced contraction in the PT‐pretreated strips. The pretreatment with PT significantly reduced 45Ca2+ uptake of the arterial strips stimulated by ET‐1, but had no effect on ET‐1‐induced production of inositol phosphates. The contractile response of the arterial strips to phorbol dibutyrate, an active phorbol ester, was not significantly affected by 10−8 m nifedipine. 6 We confirmed that the pretreatment of the tissue with PT induced ADP‐ribosylation of a 41 kDa membrane protein. 7 These findings indicate that activation of dihydropyridine‐sensitive voltage‐dependent Ca2+ channels by ET‐1 in this tissue is mediated via a PT‐sensitive G‐protein in a manner apparently independent of the ET‐1‐induced activation of protein kinase C. It is concluded that the action of ET‐1 in porcine coronary artery is mediated via two distinct signal transduction pathways, which are coupled to PT‐sensitive and PT‐insensitive GTP‐binding proteins, respectively. 1992 British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)456-462
Number of pages7
JournalBritish Journal of Pharmacology
Volume107
Issue number2
DOIs
StatePublished - Oct 1992

Keywords

  • GTP‐binding proteins
  • dihydropyridines
  • phorbol esters
  • phosphoinositides turnover

ASJC Scopus subject areas

  • Pharmacology

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