Stimulation by nitric oxide of gastric acid secretion in bullfrog fundic mucosa in vitro.
We examined the effect of NO on acid secretion in vitro using isolated preparations of Bullfrog stomach. The bullfrog fundic mucosa was bathed in unbuffered Ringer solution gassed with 100% O2 on the mucosal side and HCO3- Ringer's solution gassed with 95% O2/5% CO2 on the serosal side, and the acid secretion was measured at pH 5.0 using the pH-stat method and by adding 5 mM NaOH. Serosal addition of a NO donor NOR-3 (10(-5) approximately 10(-3) M: (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexnamine) caused an increase of acid secretion in a dose-dependent manner, the effect lasting about 1 hr and reaching a maximal level of 2-fold the basal values. The acid stimulatory effect of NOR-3 was mimicked by another NO donor SNAP (10(-3) mol/L: S-nitroso-O-N-acetyl-penicillamine) and markedly and markedly inhibited by prior administration of cimetidine (10(-5) mol/L) as well as compound 48/80 (the mast cell degranulator). Likewise, the increased acid response to NOR-3 was significantly mitigatd by pretreatment with carboxy-PTIO (a NO scavenger) or superoxide dismutase (SOD), but not by indomethacin or methylene blue (a guanylyl cyclase inhibitor). Neoither L-NAME, L-arginine nor dibutyryl guanosine-3',5'-cyclic monophosphate (dbcGMP) has any effect on the basal acid secretion. Serosal addition of NOR-3 caused a significant increase in the luminal release of histamine, and this response was inhibited by pretreatment with either compound 48/80, carboxy-PTIO or SOD. These results suggest that the NO donor increases gastric acid secretion in the isolated frog stomach in vitro, and this action is mediated by endogenous histamine released from mast cells, the process being cGMP-independent but requiring the presence of superoxide radicals. In addition, it was speculated that the histamine releasing action of NO may be due to peroxynitrite produced by NO and superoxide radicals.
Kawauchi
S
S
Department of Pharmacology & Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi,  Yamashina, Japan.
Sugamoto
S
S
Furukawa
O
O
Mimaki
H
H
Takeuchi
K
K
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005748:Gastric Fundus; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011892:Rana catesbeiana; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D001565:Benzoates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide; D003189:p-Methoxy-N-methylphenethylamine; D003994:Bucladesine; D026423:S-Nitroso-N-Acetylpenicillamine; D002927:Cimetidine; C061872:FK 409; D001120:Arginine; D013482:Superoxide Dismutase; D010396:Penicillamine; D019331:NG-Nitroarginine Methyl Ester