Mechanisms underlying capsaicin-stimulated secretion in the stomach: comparison with mucosal acidification.
The effects of capsaicin and mucosal acidification on gastric HCO3(-) secretion were compared in wild-type and prostacyclin (PGI2) IP receptor or prostaglandin E receptor EP1 or EP3 knockout C57BL/6 mice as well as rats. Under urethane anesthesia, the stomach was mounted on an ex vivo chamber, perfused with saline, and the secretion of HCO3(-) was measured at pH 7.0 using the pH-stat method. Capsaicin or 200 mM HCl was applied to the chamber for 10 min. Capsaicin increased the secretion of HCO3(-) in rats and wild-type mice, the response at 0.3 mg/ml being equivalent to that induced by acidification. This effect of capsaicin in rats was abolished by ablation of capsaicin-sensitive afferent neurons and attenuated by indomethacin, N(G)-nitro-L-arginine methylester (L-NAME), and capsazepine [transient receptor potential vanilloid type 1 (TRPV1) antagonist] but not FR172357 [3-bromo-8-[2,6-dichloro-3-[N[(E)-4-(N,N-dimethylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2-metylimidazo[1,2-a]pyridine; bradykinin B2 antagonist] or the EP1 antagonist. The acid-induced HCO3(-) secretion was attenuated by indomethacin, L-NAME, the EP1 antagonist, and sensory deafferentation, but not affected by capsazepine or FR172357. Prostaglandin E2 (PGE2), NOR-3 [(+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamine] (NO donor), and bradykinin stimulated the secretion of HCO3(-), and the effect of bradykinin was blocked by indomethacin and L-NAME as well as FR172357. The stimulatory effect of capsaicin disappeared in IP (-/-) mice, whereas that of acidification disappeared in EP1 (-/-) mice. Intragastric application of capsaicin increased mucosal PGI2 but not PGE2 levels in the rat stomach. These results suggested that both capsaicin and acid increase gastric HCO3(-) secretion via a common pathway, involving PG and NO as well as capsaicin-sensitive afferent neurons, yet their responses differ concerning TRPV1 or prostanoid receptor dependence.
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607, Japan.
Eitaro
E
Aihara
Masamune
M
Hayashi
Yoko
Y
Sasaki
Atsushi
A
Kobata
Koji
K
Takeuchi
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology; D009574:Nitro Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044006:Receptors, Epoprostenol / Q000502:physiology
D001639:Bicarbonates; D009574:Nitro Compounds; D044006:Receptors, Epoprostenol; D009569:Nitric Oxide; C061872:FK 409; D015232:Dinoprostone; D002211:Capsaicin; D001920:Bradykinin