AJP - Gastrointestinal and Liver Physiology, Vol 253, Issue 4 497-G501, Copyright © 1987 by American Physiological Society
Histamine H2-receptor of human and rabbit parietal cells
R. Leth, B. Elander, U. Haglund, L. Olbe and E. Fellenius
Sahlgren's Hospital, University of Goteborg, Sweden.
The histamine H2-receptor on the human parietal cell has been characterized
by using dose-response curves and the negative logarithm of the molar
concentration of an antagonist (pA2) analyses of cimetidine antagonism of
betazole, histamine, and impromidine stimulation in isolated human and
rabbit gastric glands. To evaluate the in vitro results,
betazole-stimulated gastric acid secretion with and without cimetidine was
also studied in healthy subjects. In the in vivo model, individual
dose-response curves were shifted to the right with increasing cimetidine
concentrations, but this was counteracted by increasing betazole doses,
indicating competitive, reversible antagonism. The pA2 values ranged from
6.1 to 6.3. In isolated human gastric glands, impromidine was shown to be
eight times more potent than histamine, indicating higher receptor
affinity, but the maximally stimulated aminopyrine accumulation was the
same as for histamine, and the pA2 values for cimetidine antagonism did not
differ significantly, i.e., 5.7 (histamine) and 6.1 (impromidine). In
isolated rabbit gastric glands, cimetidine inhibited the histamine- and
impromidine-stimulated response with pA2 values of 6.0 and 7.3,
respectively. Impromidine was shown to be approximately 100 times more
potent than in human gastric glands, whereas histamine had the same
potency. This confirms the role of the histamine H2-receptor and suggests a
difference between the species concerning receptor affinity.
