title: Involvement of L-arginine-nitric oxide pathways in neural relaxation of the sphincter of Oddi.
abstract: To evaluate if L-arginine-nitric oxide-pathways are involved in the neural relaxation of the sphincter of Oddi, we studied the effect of nitric oxide synthase inhibition on electrical field stimulation-induced relaxation of the sphincter of Oddi in the guinea pig in vitro. After incubation with atropine (1 microM), phentolamine (1 microM) and propranolol (1 microM), histamine (50 microM) and cholecystokinin-octapeptide (25 nM) produced similar increases in sphincter tone. Subsequent field stimulation induced sphincteric relaxation, that was significantly greater when the initial tone had been raised by cholecystokinin (5 Hz, 59 +/- 9%; 10 Hz, 79 +/- 9%) compared to histamine (5 Hz, 27 +/- 3%; 10 Hz, 40 +/- 7%). N-omega-Nitro-L-arginine methyl ester (L-NAME, 100 microM), which competitively inhibits nitric oxide synthase, markedly suppressed this relaxation. The subsequent addition of L-arginine (1 mM), but not D-arginine (1 mM), restored the relaxation. Hexamethonium (100 microM) did not affect the relaxation, but tetrodotoxin (1 microM) completely abolished it. Sodium nitroprusside caused a dose-dependent relaxation of the sphincter (ED50 13 nM), which was unaffected by L-NAME. In conclusion, endogenous nitric oxide synthase products represent a major transmitter of non-adrenergic non-cholinergic relaxation of the sphincter of Oddi in the guinea pig. This relaxation is partially facilitated by cholecystokinin.
authors.affiliation: Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: J G
authors.initials: JG
authors.lastname: Pauletzki
authors.forename: K A
authors.initials: KA
authors.lastname: Sharkey
authors.forename: J S
authors.initials: JS
authors.lastname: Davison
authors.forename: A
authors.initials: A
authors.lastname: Bomzon
authors.forename: E A
authors.initials: EA
authors.lastname: Shaffer
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000294:innervation
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D006632:Histamine; D002766:Cholecystokinin; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester