Does phospholipase C mediate muscarinic receptor-induced rat urinary bladder contraction?
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.
Frazier
Elfaridah P
EP
Department of Pharmacology and Pharmacotherapy, University of Amsterdam, The Netherlands.
Braverman
Alan S
AS
Peters
Stephan L M
SL
Michel
Martin C
MC
Ruggieri
Michael R
MR
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology; D009355:Neomycin / Q000494:pharmacology; D051381:Rats; D043587:Receptor, Muscarinic M3 / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology*; D001743:Urinary Bladder / Q000502:physiology*
D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D002217:Carbachol; D010738:Type C Phospholipases; D009355:Neomycin