Gastric glands isolated from rabbit were employed to perform a pharmacological characterization of the histamine receptor associated with physiological and biochemical responses in gastric cells. Five separate response parameters were characterized using histamine analogues and histamine antagonists. The following parameters were studied: respiration, accumulation of the weak base aminopyrine, adenylate cyclase activity, cAMP accumulation, and the uptake of histamine. 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 histamine receptor associated with these four parameters as being of the H2 type. Moreover, the similarity of pharmacological characteristics provides evidence for a similar, if not common, receptor for these responses. The histamine 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. Thus, 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.
- Copyright © 1980 the American Physiological Society