Distinct mechanisms of acid-induced HCO3- secretion in normal and slightly permeable stomachs.
We investigated the regulatory mechanism of acid-induced HCO(3)(-) secretion in the slightly permeable rat stomach after an exposure to hyperosmolar NaCl. Under urethane anesthesia, a rat stomach was mounted on a chamber and perfused with saline, and the secretion of HCO(3)(-) was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. Acidification of the normal stomach with 100 mM HCl increased HCO(3)(-) secretion, and this response was totally inhibited by pretreatment with indomethacin but not N(G)-nitro-l-arginine methyl ester (l-NAME) or chemical ablation of capsaicin-sensitive afferent neurons. Exposure of the stomach to 0.5 M NaCl deranged the unstirred mucus gel layer without damaging the surface epithelial cells. The stomach responded to 0.5 M NaCl by secreting slightly more HCO(3)(-), in an indomethacin-inhibitable manner, and responded to even 10 mM HCl with a marked rise in HCO(3)(-) secretion, although 10 mM HCl did not have an effect in the normal stomach. The acid-induced HCO(3)(-) response in the NaCl-treated stomach was significantly but partially attenuated by indomethacin, l-NAME, or sensory deafferentation and was totally abolished when these treatments were combined. These results suggest that gastric HCO(3)(-) secretion in response to acid is regulated by two independent mechanisms, one mediated by prostaglandins (PGs) and the other by sensory neurons and nitric oxide (NO). The acid-induced HCO(3)(-) secretion in the normal stomach is totally mediated by endogenous PGs, but, when the stomach is made slightly permeable to acid, the response is markedly facilitated by sensory neurons and NO.
Aihara
Eitaro
E
Dept. of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical Univ., Misasagi, Yamashina, Kyoto 607, Japan.
Sasaki
Yoko
Y
Ise
Fumitaka
F
Kita
Kazutomo
K
Nomura
Yoko
Y
Takeuchi
Koji
K
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006851:Hydrochloric Acid / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects
D001639:Bicarbonates; D009569:Nitric Oxide; D015232:Dinoprostone; D006851:Hydrochloric Acid