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Does Phospholipase C Mediate Muscarinic Receptor-Induced Rat Urinary Bladder Contraction?

Does Phospholipase C Mediate Muscarinic Receptor-Induced Rat Urinary Bladder Contraction?

Elfaridah P Frazier, Alan S Braverman, Stephan L M Peters, Martin C Michel, Michael R Ruggieri Sr

J Pharmacol Exp Ther. 2007 Sep;322(3):998-1002.

PMID: 17596535

Abstract:

Muscarinic acetylcholine receptors, particularly M(3) 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-[((17beta)-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-OCH(3) (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 M(3) muscarinic receptor-mediated rat bladder contraction.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP83373608-B	O-Tricyclo[5.2.1.02,6]dec-9-yl dithiocarbonate potassium salt		83373-60-8	Price
IAR4244391	1-O-Octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine			Price

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