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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Muscarinic regulation of neonatal rat bladder spontaneous contractions

¹Department of Surgery, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; ²Department of Pharmacology, University of Pittsburgh, and ³Department of Pediatric Urology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania

Submitted 4 April 2006 ; accepted in final form 15 May 2006

In vitro preparations of whole urinary bladders of neonatal rats exhibit prominent myogenic spontaneous contractions, the amplitude and frequency of which can be increased by muscarinic agonists. The muscarinic receptor subtype responsible for this facilitation was examined in the present experiments. Basal spontaneous contractions in bladders from 1- to 2-wk-old Sprague-Dawley rats were not affected by M₂ or M₃ receptor antagonists. However, administration of 0.5 µM physostigmine, an anticholinesterase agent that increases the levels of endogenous acetylcholine, or 50–100 nM carbachol, a cholinergic agonist at low concentrations, which did not cause tonic contractions, significantly augmented the frequency and amplitude of spontaneous contractions. Blockade of M₂ receptors with 0.1 µM AF-DX 116 or 1 µM methoctramine or blockade of M₃ receptors with 50 nM 4-diphenylacetoxy-N-methylpiperidine methiodide or 0.1 µM 4-diphenylacetoxy-N-(2-chloroethyl)piperidine hydrochloride (4-DAMP mustard) reversed the physostigmine and carbachol responses. M₂ and M₃ receptor blockade did not alter the facilitation of spontaneous contractions induced by 10 nM BAY K 8644, an L-type Ca²⁺ channel opener, or 0.1 µM iberiotoxin, a large-conductance Ca²⁺-activated K⁺ channel blocker. NS-1619 (30 µM), a large-conductance Ca²⁺-activated K⁺ channel opener, decreased carbachol-augmented spontaneous contractions. These results suggest that spontaneous contractions in the neonatal rat bladder are enhanced by activation of M₂ and M₃ receptors by endogenous acetylcholine released in the presence of an anticholinesterase agent or a cholinergic receptor agonist.

M₂ receptors; M₃ receptors; overactive bladder; detrusor overactivity

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				Y. Ikeda and A. Kanai Urotheliogenic modulation of intrinsic activity in spinal cord-transected rat bladders: role of mucosal muscarinic receptors Am J Physiol Renal Physiol, August 1, 2008; 295(2): F454 - F461. [Abstract] [Full Text] [PDF]

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