Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi.
Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10(-5) M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 x 10(-7) M) and oxyhaemoglobin (1.6 x 10(-5) M), but not affected by atropine (10(-7) M), propranolol (10(-7) M), phentolamine (10(-7) M), indomethacin (10(-6) M), cholecystokinin (CCK, 10(-8) M) and vasoactive intestinal polypeptide (VIP, 10(-8) M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L-NA, 10(-5) M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10(-5) M) and L-NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10(-5) M). The addition of K+ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10(-3) M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used.
Tanobe
Y
Y
Department of Pharmacology, Shiga University of Medical Science, Ohtsu, Japan.
Okamura
T
T
Fujimura
M
M
Toda
N
N
D000704:Analysis of Variance; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005069:Evaluation Studies as Topic; D005260:Female; D006651:Histocytochemistry; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009252:NADPH Dehydrogenase / Q000032:analysis*; D009412:Nerve Fibers / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology*; D009803:Sphincter of Oddi / Q000294:innervation*; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects
D009569:Nitric Oxide; D009538:Nicotine; D009252:NADPH Dehydrogenase; D011188:Potassium