Antagonistic effect of mepyramine and tubocurarine on the histamine-mediated contraction of intestinal smooth muscle cells

Abstract

Introduction: Histamine is an endogenous ligand which exerts its biological actions by binding to 4 subtypes of histamine receptors (HR). Its effects on the gastrointestinal tract are complex being the dominant effect contraction of muscle cells. Method: The aim of this study was to verify the antagonistic effect of mepyramine (10-10M - 10-7M) and tubocurarine (10-7M - 10-4M) in the contractile action of histamine (10-11M - 10-4M). in guinea pig ileum, for this purpose it was used the program Virtual Organ Bath 16 V 2.8, which allow quantify the change in strength(g) produced by smooth muscle contraction in the presence of these substances. Concentration-response curves were obtained through GraphPad Prism® graphic program. The determination of the competitive nature of the antagonist and the calculation of the affinity constant was performed through Schild method. Results: Mepyramine is a competitive antagonist of histamine (10-10M to 10-7M), making it a potential therapeutic agent for the treatment of irritable bowel syndrome. On the other hand, it is not understood that tubocurarine is an antagonist of histamine receptors. Conclusions: The results obtained provide evidence that the contractile effect of histamine on the smooth muscle of intestinal cells isolated from guinea pig is competitively antagonized by mepyramine. In addition, by calculating the pKB parameter, it was found that this compound has greater potency than other antihistamines.