Regulation of expression of the receptors controlling gastric acidity.

Abstract

Gastric acid secretion is regulated by the stimulatory effects of gastrin, histamine and acetylcholine and the inhibitory actions of somatostatin on their respective receptors. We proposed that the expression of these receptors could be regulated at the transcription level by agonists and antagonists known to effect acid secretion. A quantitative "real-time" PCR method was used to determine changes in mRNA expression for these receptors. The agonists, pentagastrin and histamine, and the H2 antagonist, ranitidine, were infused over a 6 h period to conscious sheep. Blood, antral and fundic tissue samples were taken for analysis. Both pentagastrin and histamine resulted in elevated plasma somatostatin concentrations during the treatment. Ranitidine stimulated a fourfold increase in plasma gastrin while histamine caused a transient decrease. Except for an increase in antral gastrin following ranitidine infusion, there was no significant change in gastric gastrin and somatostatin concentration. Histamine (H2) receptor mRNA expression in the antrum was significantly increased by pentagastrin and decreased by ranitidine. Pentagastrin also stimulated a significant increase in the level of muscarinic (M3) receptor mRNA in the antrum. Antral somatostatin II receptor mRNA was significantly decreased by histamine. In the fundus, pentagastrin infusion resulted in a significant increase in histamine receptor mRNA and a decrease in the muscarinic receptor mRNA. This work demonstrates that the receptors involved in the regulation of acid secretion can be regulated by local events.