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Pharmacology of carbachol induced phasic contractions in isolated guinea pig bladder: M 2 or M 3
Author(s) -
Srinivasan Dinesh,
Kim Jong Moo,
Burbach Leah R.,
Ford Anthony P.D.W.,
Bhattacharya Anindya
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a660-b
Subject(s) - carbachol , muscarinic acetylcholine receptor , tonic (physiology) , antagonist , guinea pig , atropine , muscarinic antagonist , endocrinology , chemistry , medicine , contraction (grammar) , pirenzepine , muscarinic acetylcholine receptor m2 , urinary bladder , receptor , receptor antagonist , biology
The isolated guinea pig whole bladder has been shown to exhibit phasic contractions which are amplified by carbachol (CCh) and may represent a model of human bladder overactivity (Gillespie, 2004). Atropine, a non‐selective muscarinic receptor antagonist has been shown to inhibit the phasic contractions but the individual contributions of muscarinic receptor subtypes have not been determined. Of the five muscarinic receptor subtypes, M 2 and M 3 receptors are expressed in bladder smooth muscle. The objective of the present study was to characterize their relative contributions to the tonic and phasic contractions. The isolated whole bladder was stimulated with 1 μM CCh to induce an initial tonic contraction followed by phasic contractions. We observed that the tonic contraction to CCh desensitized but the phasic contractions did not. Both, AF‐DX 116, M 2 selective antagonist (pK i 6.27 ± 0.1) at 0.3, 3 and 30 μM and DAU 5884, M 3 selective antagonist (pKi 9.05 ± 0.09) at 1, 10 and 100 nM, attenuated the amplitude of phasic contractions in a concentration dependent manner. Only AF‐DX 116 inhibited the frequency in a concentration dependent manner. Interestingly, similar results were obtained from guinea pig bladder strips suggesting that the cell‐types generating CCh‐induced phasic activity may be ubiquitously distributed. Although intriguing, the physiological relevance of this study to human bladder overactivity needs to be established. Nonetheless, both M 2 and M 3 receptor subtypes appear to be involved in the maintenance of CCh‐induced phasic contractions in the isolated guinea pig bladder.