Mechanisms Underlying Capsaicin-Stimulated Secretion in the Stomach: Comparison with Mucosal Acidification

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 315; no. 1; pp. 423 - 432
• Main Authors: Aihara, Eitaro, Hayashi, Masamune, Sasaki, Yoko, Kobata, Atsushi, Takeuchi, Koji
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.10.2005
• Subjects: Animals; Bicarbonates - metabolism; Bradykinin - pharmacology; Capsaicin - pharmacology; Dinoprostone - pharmacology; Gastric Mucosa - drug effects; Gastric Mucosa - secretion; Hydrogen-Ion Concentration; Male; Mice; Nitric Oxide - physiology; Nitro Compounds - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Epoprostenol - physiology
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.105.087619

The effects of capsaicin and mucosal acidification on gastric 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 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 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 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 , 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 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.