Muscarinic regulation of neonatal rat bladder spontaneous contractions.
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.
Ng
Yuen-Keng
YK
Department of Surgery, University of Hong Kong, Hong Kong.
de Groat
William C
WC
Wu
Hsi-Yang
HY
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology; D004558:Electric Stimulation; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009122:Muscle Hypertonia / Q000503:physiopathology; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D001743:Urinary Bladder / Q000294:innervation* / Q000502:physiology*
D002120:Calcium Channel Agonists; D018679:Cholinergic Agonists; D002800:Cholinesterase Inhibitors; D003959:Diamines; D010276:Parasympatholytics; D010455:Peptides; D010880:Piperidines; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D010890:Pirenzepine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C064719:iberiotoxin; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol; D010830:Physostigmine; C054938:methoctramine; C048593:otenzepad