Regulation of protein kinases in steady-state contraction of cat gastric smooth muscle

Eur J Pharmacol. 1997 Apr 18;324(2-3):205-10. doi: 10.1016/s0014-2999(97)00083-6.

Abstract

Cat gastric smooth muscle strips were used to investigate the involvement of protein kinases in the steady-state contraction induced by 1 microM acetylcholine or 20 mM KCI. The steady-state contraction induced by acetylcholine or KCl was inhibited by EGTA dose dependently. Voltage-dependent Ca2+ channel antagonists dose dependently inhibited the contractions induced by KCI as well as by acetylcholine. Inhibitory effects of voltage-dependent Ca2+ channel antagonists were significantly more prominent on KCI-induced contractions than on acetylcholine-induced contractions. The acetylcholine-induced contraction was dose dependently inhibited by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8, a blocker of intracellular Ca2+ release), but the KCl-induced contraction was not inhibited at all. Therefore both intracellular Ca2+ release and extracellular Ca2+ influx seem to be necessary for the acetylcholine-induced contraction, but intracellular Ca2+ release is not necessary for the KCl-induced contraction. Protein kinase C inhibitors, 10 microM 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine 2HCl (H-7) and 1 microM staurosporine, significantly inhibited the contraction induced by acetylcholine or KCl. Calmodulin antagonists, 30 microM trifluoperazine and 50 microM N-(6-aminohexyl)-5-chloro-2-naphthalenesulfonamide HCI (W-7), however, significantly inhibited the contraction induced by acetylcholine but not by KCl. A tyrosine kinase inhibitor, 50 microM genistein, did not affect the acetylcholine-induced contraction but significantly inhibited the KCl-induced contraction. These results strongly suggest that the involvement of protein kinases in regulation of the steady-state contraction may be agonist-dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / antagonists & inhibitors
  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology*
  • Calmodulin / drug effects
  • Cats
  • Female
  • Male
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Potassium Chloride / antagonists & inhibitors
  • Protein Kinase C / antagonists & inhibitors*
  • Stomach

Substances

  • Calcium Channel Blockers
  • Calmodulin
  • Potassium Chloride
  • Protein Kinase C
  • Acetylcholine
  • Calcium