Muscarinic regulation of neonatal rat bladder spontaneous contractions

Abstract

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 microM 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 microM AF-DX 116 or 1 microM methoctramine or blockade of M3 receptors with 50 nM 4-diphenylacetoxy-N-methylpiperidine methiodide or 0.1 microM 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 microM iberiotoxin, a large-conductance Ca2+-activated K+ channel blocker. NS-1619 (30 microM), 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.

Suppression of human detrusor smooth muscle excitability and contractility via pharmacological activation of large conductance Ca2+-activated K+ channels

“…5). Our data on human DSM are consistent with the earlier findings that NS-1619 causes a decrease in the carbachol-induced contractions in rat DSM (30,38).…”

Differential Effect of l-Cysteine in Isolated Whole-Bladder Preparations from Neonatal and Adult Rats

“…Rats were anesthetized with halothane and sacrificed by cervical dislocation. A whole-bladder preparation was prepared by using previously published techniques (Sugaya and de Groat, 2000;Ng et al, 2006). The bladder was exposed by a midline abdominal incision and removed from the abdomen by cutting at the bladder neck.…”

“…The exposure time of each L-cysteine application was 10 min. In some experiments, the effects of various agents, including the thiol-modifying agent diamide (200 M), the L-type calcium channel blocker nifedipine (1 M), the nitric-oxide (NO) synthase inhibitor N -nitro-Larginine (100 M), the purinergic agonist ATP (50 M), the purinergic antagonist suramin (200 M), or the calcium-activated K wards et al, 1994;Patel et al, 1998;Ng et al, 2006;Park et al, 2007;30 M), were examined during recording of spontaneous contractions in the presence or absence of L-cysteine (1 mM). In our preliminary studies, we tested different concentrations of diamide and determined that 200 M was a suitable concentration to obtain a reproducible inhibitory effect on the responses to L-cysteine.…”

Maturation of stretch‐induced contractile activity and its muscarinic regulation in isolated whole bladder strips from rat

“…4,5,16 Here we show that this CA-mediated response of SIC (normalized to CSA) is significantly increased in early neonatal rat bladder (D0), with increased effects on amplitude of stretch-induced contractions (equals phasic activity) but not on baseline tension (equals tonic activity). These observations have been similarly reported before.…”