gingerol and lafutidine

Effects of vanilloid-receptor agonists and antagonists on HCl-induced gastric lesions in rats were investigated to elucidate the role of vanilloid receptor type 1 (VR1) in gastric mucosal defense mechanisms.. Gastric lesions in rats were evaluated after intragastric administration of 0.6 N HCl. The localization of VR1 in the stomach was investigated immunohistochemically.. Intragastric administration of capsaicin inhibited the formation of gastric lesions in a dose-dependent manner (0.1-2.5 mg/kg). The functional VR1 antagonists ruthenium red and capsazepine markedly aggravated HCl-induced gastric lesions in rats. The gastroprotective effect of capsaicin was attenuated by ruthenium red or capsazepine. It is reported that resiniferatoxin, [6]-gingerol and lafutidine are compounds that activate VR1 and/or capsaicin-sensitive afferent neurons. These compounds significantly inhibited the formation of HCl-induced gastric lesions, and their gastroprotective effects were inhibited by treatment with ruthenium red. The immunohistochemical studies revealed that nerve fibers expressing VR1 exist along gastric glands in the mucosa, around blood vessels in the submucosa, in the myenteric plexus, and in the smooth muscle layers, especially the circular muscle layer.. The results of this study suggest that VR1 plays a protective role in the gastric defensive mechanism in rats.

Topics: Acetamides; Animals; Anti-Ulcer Agents; Capsaicin; Catechols; Diterpenes; Famotidine; Fatty Alcohols; Gastric Mucosa; Hydrochloric Acid; Male; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, Drug; Stomach Ulcer

A segment of guinea pig ileum was used to confirm the hypothesis that [6]-gingerol and lafutidine interact with capsaicin-sensitive neurons. Addition of 30 and 100 microM [6]-gingerol (a pungent constituent of ginger) induced contraction of the ileum immediately. Like capsaicin, [6]-gingerol-induced contraction was inhibited by antagonists of the vanilloid receptor (capsazepine and ruthenium red), tetrodotoxin, and atropine. Treatment with [6]-gingerol up to 0.3 microM, which alone had no effect, enhanced 3 microM capsaicin-induced contraction, but greater than 3 microM [6]-gingerol significantly inhibited capsaicin-induced contraction. Treatment with lafutidine (a new type of antagonist of the histamine H(2) receptor), which was suggested to interact with capsaicin-sensitive neurons in vivo, also showed both stimulatory and inhibitory effects on capsaicin-induced contraction depending on the concentrations. Lafutidine alone had no effect. The enhanced contraction induced by capsaicin in the [6]-gingerol- or lafutidine-treated ileum was also inhibited by antagonists of the vanilloid receptor, tetrodotoxin, and atropine. Capsaicin and [6]-gingerol, but not lafutidine, at 30 microM stimulated [(3)H]choline release from the prelabeled slices of the ileum. These findings suggest that [6]-gingerol and lafutidine act on capsaicin-sensitive cholinergic neurons and modulate the contraction in isolated guinea pig ileum.

Topics: Acetamides; Animals; Capsaicin; Catechols; Dose-Response Relationship, Drug; Fatty Alcohols; Guinea Pigs; Ileum; In Vitro Techniques; Male; Muscle Contraction; Neurons; Piperidines; Pyridines