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The actions of prolonged exposure to cholinergic agonists on isolated bladder strips from the rat

Lookup NU author(s): Professor James Gillespie

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Abstract

The present study was done to explore the cholinergic systems operating in the wall of the isolated rat bladder. In a first set of experiments, bladder strips in vitro were subjected to cumulative concentration-response curve (CRC) to non-selective muscarine agonist carbachol or the partially M2 > M3 selective agonist arecaidine to establish optimal concentration to be used thereafter. In a second set of experiments, the effects of drugs (solifenacin, isoproterenol, and mirabegron) were tested on urinary bladder contraction induced by the non-selective muscarinergic agonist carbachol. For both agonists, the contractile responses are qualitatively similar: an initial transient rise in tension followed by complex bursts of high-frequency small 'micro'-contractions superposed on a tonic contraction, with immediate transient 'rebound' contraction after the agonist is washed from the preparation. This rebound contraction is greater with carbachol than arecaidine. Components of the responses to cholinergic stimulation, notably the micro-contractions, were found to be differently stimulated and inhibited by the M3 > M2 selective antagonist solifenacin and by the beta-adrenoceptor agonists isoprenaline and mirabegron. A physiological role for the muscarinic dependent phasic contractions and the micro-anatomical elements that might be involved are not known but may be related to non-voiding activity observed during filling cystometry in conscious animals related to afferent discharge and possibly sensation. Furthermore, suggestions for the potential impact of these findings and design of further studies in relation to bladder physiology, pharmacology, and pathology are discussed.

Publication metadata

Author(s): Gillespie JI, Rouget C, Palea S, Korstanje C

Publication type: Article

Publication status: Published

Journal: Naunyn-Schmiedeberg's Archives of Pharmacology

Year: 2015

Volume: 388

Issue: 7

Pages: 737-747

Print publication date: 01/07/2015

Online publication date: 17/05/2015

Acceptance date: 03/05/2015

ISSN (print): 0028-1298

ISSN (electronic): 1432-1912

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00210-015-1129-y

DOI: 10.1007/s00210-015-1129-y

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