Mechanisms underlying capsaicin-stimulated HCO3- 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 (PGI(2)) 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 E-2 (PGE(2)), 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 PGI(2) but not PGE(2) 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.