Ca2+ channel blockers distinguish between G protein-coupled pharmacomechanical Ca2+ release and Ca2+ sensitization

S. Kobayashi, M. C. Gong, A. V. Somlyo, A. P. Somlyo

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

The effects of Ca2+ channel blockers on two modes of G protein-mediated pharmacomechanical coupling, Ca2+ release and modulation of Ca2+ sensitivity of the contractile apparatus, were investigated. Smooth muscles were permeabilized with Staphylococcal α-toxin or with β-escin to avoid effects due to block of sarcolemmal Ca2+ channels, while retaining receptor/G protein coupling. In permeabilized portal vein smooth muscle, verapamil and nifedipine inhibited Ca2+ release induced by an α1-adrenergic agonist (phenylephrine) and by guanosine 5'-O-(3-thiotriphosphate) (GTPγS), but not that induced by inositol 1,4,5-trisphosphate (InsP3). These Ca2+ channel blockers also did not block the phenylephrine- or GTPγS-induced force development at constant cytoplasmic Ca2+ (''Ca2+ sensitization''). An α1-blocker (prazosin) inhibited both the Ca2+-releasing and Ca2+-sensitizing effects of phenylephrine, but not those of GTPγS, nor did it block InsP3-induced Ca2+ release. We conclude that Ca2+ channel blockers selectively uncouple the Ca2+-releasing, but not the Ca2+-sensitizing, component of pharmacomechanical coupling. These findings raise the possibility that pharmacomechanical Ca2+ release may be modulated by dihydropyridine binding proteins at the level of G proteins/phospholipase C and also indicate a divergence of the Ca2+-releasing and Ca2+-sensitizing effects at some step prior to phospholipase C.

Original languageEnglish
Pages (from-to)C364-C370
JournalAmerican Journal of Physiology - Cell Physiology
Volume260
Issue number2 29-2
DOIs
StatePublished - 1991

Keywords

  • Guanosine 5'-triphosphate-binding protein
  • Sarcoplasmic reticulum
  • Signal transduction
  • Smooth muscle
  • Verapamil
  • α-Toxin
  • β-Escin

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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