Effect of extracellular Ca2+ on cholinergic, KCl and phorbol ester-mediated phosphoinositide turnover and guinea pig urinary bladder contraction.

Abstract

The effect of extracellular Ca2+ ([Ca2+]o) on cholinergic, KCl and phorbol ester-mediated detrusor contractions was related to phosphoinositide (PI) breakdown in guinea pig urinary bladder. Carbachol (1.0 mM) elicited a 20-fold increase in inositol phosphate (IP) accumulation both in presence and absence of [Ca2+]o yielding the same EC50 value (approximately 12 microM). In contrast, carbachol-induced detrusor contractions were reduced by 35% without [Ca2+]o, but maximal efficacy was restored with Ca2+ replenishment. In absence of [Ca2+]o, repeated cholinergic stimulation yielded contractions only if tissues were intermittently equilibrated in [Ca2+]o. High K+ and PDBu evoked [Ca2+]o-dependent contractions. Ca2+ channel antagonists and divalent metal cations inhibited high K+ more potently than carbachol-mediated contractions. Together, these findings suggest multiple sources of Ca2+ for urinary bladder contraction, where voltage-sensitive responses depend primarily on [Ca2+]o and PI-linked muscarinic responses involved Ca2+ mobilization from intracellular stores as well. Clinical agents used for the treatment of urinary incontinence inhibited both carbachol-induced PI turnover and muscle contraction with the same rank order of potency both in presence and absence of [Ca2+]o. These findings suggest that the cholinergic mechanism of action of these agents involves the PI-Ca2+ effector system.

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@article{Lowe1991EffectOE, title={Effect of extracellular Ca2+ on cholinergic, KCl and phorbol ester-mediated phosphoinositide turnover and guinea pig urinary bladder contraction.}, author={Valeria Lowe and Lalita Noronha-Blob}, journal={European journal of pharmacology}, year={1991}, volume={195 2}, pages={273-9} }