PT  - JOURNAL ARTICLE
AU  - Elfaridah P. Frazier
AU  - Alan S. Braverman
AU  - Stephan L. M. Peters
AU  - Martin C. Michel
AU  - Michael R. Ruggieri, Sr.
TI  - Does Phospholipase C Mediate Muscarinic Receptor-Induced Rat Urinary Bladder Contraction?
AID  - 10.1124/jpet.107.125393
DP  - 2007 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 998--1002
VI  - 322
IP  - 3
4099  - http://jpet.aspetjournals.org/content/322/3/998.short
4100  - http://jpet.aspetjournals.org/content/322/3/998.full
SO  - J Pharmacol Exp Ther2007 Sep 01; 322
AB  - Muscarinic acetylcholine receptors, particularly M3 receptors, are physiologically the most important mechanism to induced urinary bladder smooth muscle contraction. Their prototypical signaling response is a stimulation of phospholipase C (PLC), and this also has been shown in the urinary bladder. Nevertheless, it has remained controversial whether PLC signaling mediates bladder contraction induced by muscarinic receptor agonists. Studies in favor and against a role for PLC differed in their experimental protocol (single versus repeated concentration-response curves within a single preparation) and in the PLC inhibitors that have been used. We have now tested whether previous differential conclusions regarding a role for PLC are related to inhibitors and/or experimental protocols. In a single curve protocol, U-73,122 [1-[6-[((17β)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione] did not attenuate carbachol responses. In a repeated curve protocol, ET-18-OCH3 (1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine) lacked significant inhibition relative to vehicle time controls. In contrast, D609 (O-tricyclo[5.2.1.02,6]dec-9-yl dithiocarbonate potassium salt) depressed maximal carbachol effects but also nonspecifically inhibited contraction induced by KCl. Neomycin did not affect the carbachol-induced rat urinary bladder contraction. We conclude that previously reported differences relate to the use of inhibitors rather than experimental protocols and that the overall data do not support a role for PLC in M3 muscarinic receptor-mediated rat bladder contraction.