Histamine Receptor Effects on Dissipation of an Intracellular Proton Gradient of Isolated Gastric Mucosal Surface Cells 1

Abstract

The effects of histamine and several H₁ and H₂ receptor agents on Na⁺/H⁺ and Cl^-/HCO^- ₃ exchange systems of isolated gastric mucosal surface cells were studied. The cells were acid-loaded by the NH₄Cl prepulse technique and the spontaneous Na⁺- and HCO^- ₃-induced dissipation of the intracellular proton gradient (pH_i) was followed using the metachromatic dye acridine orange. Histamine (10^-2-5 M) stimulates HCO^- ₃-induced dissipation of the pH_i but has no effect on Na⁺-induced or spontaneous dissipation. The H₁ agonist 2-(2-aminoethyl)pyridine and the H₂ agonist dimaprit also have no effect on Na⁺-induced or spontaneous pH_i dissipation. However, both of these agents mimic the effect of histamine on HCO^- ₃-induced dissipation, but only at a higher concentration (10^-3 M). The combination of 2-(2-aminoethyl)pyridine and dimaprit produces a histamine-like effect at lower concentrations (10^-5 and 10^-4 M). The effects of histamine are blocked by either the H₁ antagonists diphenhydramine and pyrilamine or the H₂ antagonists cimetidine and SKF 93479. The results suggest that the effect of histamine on HCO^- ₃-induced dissipation of a pH_i in gastric mucosal surface cells is mediated through a coordinated mechanism involving both H₁ and H₂ receptor sites.