Local Anesthetics (Benzyl Alcohol, Lidocaine, Procainamide) Inhibit Aminopyrine Accumulation in Isolated Rat Parietal Cells

Abstract

The present studies were desgined to examine the effect of local anesthetics (benzyl alcohol, lidocaine, and procainamide) on the secretory response of parietal cells to histamine, dbcAMP, and carbachol. Studies were performed in vitro using isolated cells from rat stomachs, and acid production was determined by ¹⁴C-aminopyrine accumulation. In addition, the (H⁺-K⁺)-ATPase activity of microsomal vesicles isolated from parietal cells was determined. Lower concentrations of the drugs studied increased the basal aminopyrine accumulation and potentiated the secretory response of parietal cells to histamine and dbcAMP. At higher concentrations local anesthetics progressively inhibited both the basal ¹⁴C-aminopyrine accumulation and that stimulated by histamine, dbcAMP or carbachol. While a low concentration of local anesthetics increased gastric microsomal (H⁺-K⁺)-ATPase activity, higher concentrations inhibited enzyme activity to about 80% of those activities found in resting parietal cells. We conclude that increased aminopyrine accumulation may reflect the activation of membrane-bound enzyme(s) involved in the cAMP-dependent signal transduction pathway mediating acid secretion by parietal cells. In turn, it is possible that the inhibition of aminopyrine accumulation by local anesthetics at higher concentrations can relate to two different mechanisms: (1) the nonspecific effect of local anesthetics that causes simple proton neutralization (as weak bases), and (2) to a minor extent their inhibitory effect on proton pump activity.