Phospholipase C mediated Ca2+ signals in murine urinary bladder smooth muscle

Eur J Pharmacol. 2009 May 21;610(1-3):106-9. doi: 10.1016/j.ejphar.2009.03.036. Epub 2009 Mar 19.

Abstract

Muscarinic stimulation of urinary bladder induces contraction via an increase in intracellular Ca(2+) concentration that results from Ca(2+) influx through Ca(2+) channels and/or IP(3)-mediated Ca(2+) release controlled by phospholipase C (PLC) signalling. The significance of PLC/IP(3) signalling in this cascade has recently been questioned because PLC inhibitors were without effect on carbachol-induced contractions in detrusor muscle strips. However, PLC/IP(3)-mediated Ca(2+) release was clearly observed in recordings of Ca(2+) signals in isolated myocytes. Therefore, we investigated the presence of PLC/IP(3)-dependent Ca(2+) release by directly monitoring Ca(2+) signals in intact detrusor muscle strips. Concomitant Ca(2+) signals from Ca(2+) channel activity were eliminated by the Ca(2+) channel antagonist isradipine (3 microM) or by the use of muscles from Ca(v)1.2 channel-deficient (SMACKO) mice. In absence of Ca(2+) channel activity, carbachol elicited contractions and Ca(2+) signals in muscles from wild type and SMACKO mice that were inhibited by the PLC inhibitor U73122 (10 microM). The results show that PLC/IP(3)-dependent Ca(2+) release is activated by stimulation with carbachol in urinary bladder smooth muscle but has a minor contribution to overall carbachol-induced Ca(2+) signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Carbachol / antagonists & inhibitors
  • Carbachol / pharmacology
  • Cholinergic Agonists / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Estrenes / pharmacology
  • Isradipine / pharmacology
  • Mice
  • Mice, Knockout
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Pyrrolidinones / pharmacology
  • Signal Transduction / drug effects*
  • Time Factors
  • Type C Phospholipases / metabolism*
  • Urinary Bladder / drug effects*
  • Urinary Bladder / metabolism

Substances

  • Calcium Channel Blockers
  • Cholinergic Agonists
  • Enzyme Inhibitors
  • Estrenes
  • Pyrrolidinones
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Carbachol
  • Type C Phospholipases
  • Calcium
  • Isradipine