Phospholipase C mediated Ca2+ signals in murine urinary bladder smooth muscle.
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.
Frei
Eva
E
Institut für Pharmakologie und Toxikologie, TU München, Biedersteiner Str. 29, D-80802 München, Germany.
Hofmann
Franz
F
Wegener
Jörg W
JW
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D017275:Isradipine / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
D002121:Calcium Channel Blockers; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D002217:Carbachol; D010738:Type C Phospholipases; D002118:Calcium; D017275:Isradipine