Dual role of nitric oxide in gastric hypersecretion in the distended stomach: inhibition of acid secretion and stimulation of pepsinongen secretion.
OBJECTIVE
We investigate the role of nitric oxide (NO) in the hypersecretion of acid and pepsinogen induced by stomach distension.


METHODS
The rat stomach was distended by instillation of saline through an acute fistula under urethane anesthesia.


RESULTS
Both secretions of acid and pepsinogen were increased by the distension depending on the volume of saline introduced, and responses were attenuated by bilateral cervical vagotomy or prior administration of atropine. N(G)-nitro-l-arginine methyl ester (L-NAME) had a dual effect on these responses, causing an increase in the acid response and a decrease in the pepsin response, both in an l-arginine-sensitive manner. Distension of the stomach increased the luminal NO release; this response was suppressed by vagotomy and L-NAME. Intragastric application of FK409, a NO donor, dose-dependently increased pepsinogen secretion while decreasing acid secretion in the stomach without distension. However, serosal application of both FK409 and 8-bromo-guanosine cyclic 3', 5'-monophosphate (8-Br-cGMP) stimulated the secretion of pepsinogen in isolated mouse stomachs in vitro. The stimulatory effect of FK409 on pepsinogen secretion was totally abolished by LY83583, a guanylate cyclase inhibitor.


CONCLUSIONS
Distension of the stomach increases both acid and pepsinogen secretion through a vagal-cholinergic pathway in addition to the luminal release of NO, and NO affects these responses in opposite ways, suppressing the acid response while enhancing the pepsin response, both mediated by a guanylate cyclase/cGMP pathway.
Ito
Yasuyuki
Y
Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Okuda
Sayaka
S
Ohkawa
Fumikazu
F
Kato
Shinichi
S
Mitsufuji
Shoji
S
Yoshikawa
Toshikazu
T
Takeuchi
Koji
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D013271:Gastric Dilatation / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D020116:Pepsinogen A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000294:innervation; D014628:Vagotomy
D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D001285:Atropine; D020116:Pepsinogen A