Histamine responsiveness of isolated gastric glands

Abstract

Gastric glands isolated from rabbit were employed to perform a pharmacological characterization of the histamine [HM] receptor associated with physiological and biochemical responses in gastric cells. Five separate response parameters were characterized using HM analogs and HM antagonists. The following parameters were studied: respiration, accumulation of the weak base aminopyrine, adenylate cyclase activity, cyclic[c]AMP accumulation, and the uptake of HM. All parameters were examined for agonist and antagonist potency using dose-response curves, ED50 and pA2 values. Comparison of the ED50-agonist and pA2-cimetidine values showed a remarkable similarity for respiration, aminopyrine accumulation, adenylate cyclase activity, and cAMP accumulation. The agonist potency sequence and pA2 values for H2- vs. H1-receptor antagonists characterized the HM receptor associated with these 4 parameters as being of the H2 type. The similarity of pharmacological characteristics provides evidence for a similar, if not common, receptor for these responses. The HM uptake system shows a generally lower affinity for most agonists. Although the general agonist potency sequence is similar to the other parameters, notable exceptions were found for antagonists and the typical H2-agonist, dimaprit. The uptake system does not appear to be related directly to the activation of secretion and the carrier binding site cannot be simply defined by H1 or H2 properties.