Ya-hom, a Thai herbal remedy, has opposing effects on histaminergic and cholinergically mediated acid secretory related responses in gastric glands isolated from rabbits

Abstract

Ya-hom, a Thai traditional medicine, is used as a treatment for gastric discomfort. We previously found that Ya-hom inhibits both histamine and carbachol-stimulated acid secretion in gastric fistula rats. Herein, we used isolated gastric glands and highly enriched parietal cells from rabbit to determine whether or not Ya-hom acts directly on the acid-secreting parietal cell. Ya-hom inhibited carbachol-stimulated [14C] aminopyrine (AP) accumulation in rabbit gastric glands and prevented carbachol-induced elevation of [Ca2+]i in parietal cells. In contrast, Ya-hom potentiated histamine-stimulated AP accumulation and increased the stimulatory effect of the specific adenylyl cyclase activator, forskolin, in the presence of the histamine H2 receptor antagonist, cimetidine. Ya-hom had no effect on downstream cAMP-dependent signaling events including phosphorylation of LASP1 (LIM and SH3 domain protein 1), and F-actin redistribution. Because the cholinergic signaling pathway is mediated via calcium-dependent mechanisms, we compared effects of Ya-hom on carbachol-induced elevation of [Ca2+]i with those of thapsigargin, a specific endoplasmic reticulum Ca2+ pump inhibitor that also potentiates histamine-stimulated AP accumulation. Both agents similarly potentiated histamine-stimulated AP accumulation and their actions were not additive. Furthermore, Ya-hom inhibited thapsigargin-induced elevation of [Ca2+]i. Based on these findings, we postulate that Ya-hom induces a slow release of calcium from intracellular stores thereby suppressing the cholinergic response and potentiating the cAMP signaling pathway linked to the histamine response. Since Ya-hom directly inhibits the stimulatory effect of carbachol on acid secretion, the gastric action of this herbal remedy may target vagally-dependent HCl secretion.