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Relaxing Effect of Acetylcholine on Phenylephrine-Induced Contraction of Isolated Rabbit Prostate Strips Is Mediated by Neuronal Nitric Oxide Synthase

대한비뇨기과학회지 2013년 54권 5호 p.333 ~ 338
 ( Nguyen Hoai Bac ) - Viet Duc University Hospital Department of Urology

 ( Lee Shin-Young ) - Seoul Medical Center Department of Urology
 ( Park Soo-Hyun ) - Chung-Ang University College of Medicine Department of Physiology
 ( Lee Moo-Yeol ) - Chung-Ang University College of Medicine Department of Physiology
 ( Chang In-Ho ) - Chung-Ang University College of Medicine Department of Urology
 ( Myung Soon-Chul ) - Chung-Ang University College of Medicine Department of Urology

Abstract


Purpose: The location of acetylcholinesterase-containing nerve fibers suggests a role for acetylcholine in both contractility and secretion in the prostate gland. The colocalization of nitrergic nerves with cholinergic nerves, and the cotransmission of nitric oxide with acetylcholine in cholinergic nerves, has been demonstrated in the prostate glands of various species. Thus, we investigated the effects of acetylcholine on phenylephrine-induced contraction and the correlation between cholinergic transmission and nitric oxide synthase by using isolated prostate strips of rabbits.

Materials and Methods: Isolated prostate strips were contracted with phenylephrine and then treated with cumulative concentrations of acetylcholine. Changes in acetylcholine-induced relaxation after preincubation with NG-nitroarginine methyl ester, 7-nitroindazole, and aminoguanidine were measured. The effects of selective muscarinic receptor antagonists were also evaluated.

Results: In the longitudinal phenylephrine-contracted strip, the cumulative application of acetylcholine (10-9 to 10-4 M) elicited a concentration-dependent relaxation effect. Acetylcholine-induced relaxation was inhibited not only by nitric oxide synthase inhibitors (10 μM L-NAME or 10 μM 7-nitroindazole) but also by 10 μM atropine and some selective muscarinic receptor antagonists (10-6 M 11-([2-[(diethylamino)methyl]-1-piperdinyl]acetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one and 10-6 M 4-diphenylacetoxy-N-methyl-piperidine). In contrast, relaxation was significantly increased by pretreatment of the strips with 10 mM L-arginine.

Conclusions: Acetylcholine relaxed phenylephrine-induced contractions of isolated rabbit prostate strips. This relaxation may be mediated via both cholinergic and constitutive nitric oxide synthase with both the M2 and M3 receptors possibly playing key roles.

키워드

Acetylcholine;Muscarinic M2 receptor;Muscarinic M3 receptor;Nitric oxide synthase type I;Prostate
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