Interaction of histamine with gastric mucosal cells. Effect of histamine H2 antagonists on binding and biological response.
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Biomedical subjects
Publications and source records attributed to J Dyer.
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The role of cyclic nucleotides in regulating acid secretion by dispersed mucosal cells from guinea-pig stomach was examined by measuring first the ability of histamine and carbachol to stimulate [dimethylamine-14C]aminopyrine uptake and cyclic nucleotide metabolism and secondly, the effect of exogenous cyclic nucleotides on basal and stimulated [14C]aminopyrine uptake. The [14C]aminopyrine was found in an acidic, osmotically sensitive compartment, probably associated with the initial steps in acid secretion by these cells. Although histamine increased [14C]aminopyrine uptake and cyclic AMP synthesis as expected, histamine was approx. 10-fold more potent in inducing [14C]aminopyrine uptake. This dissociation of [14C]aminopyrine uptake and cyclic AMP metabolism process was further manifested by the observation that prostaglandin E1 failed to increase [14C]aminopyrine uptake, although it did cause a rise in cellular cyclic AMP. Furthermore, prostaglandin E1 did not alter the [14C]-aminopyrine uptake caused by histamine. Carbachol was found to increase the [14C]aminopyrine uptake and also to potentiate the ability of histamine to increase [14C]aminopyrine uptake. Carbachol, however, affected neither the histamine-induced increase in cyclic AMP nor the binding of [3H]histamine to the cells. Cimetidine, a histamine H2 receptor antagonist, blocked the [14C]aminopyrine uptake induced either by histamine alone or by the potentiating combination of histamine plus carbachol. These results suggest that cyclic AMP is mediating the action of histamine on [14C]aminopyrine uptake but changes in cyclic AMP per se are not necessarily the cause for the potentiated increase in [14C]aminopyrine uptake. Furthermore, the potentiated response observed with histamine plus carbachol on [14C]aminopyrine uptake occurs at a biochemical step distal to and not obviously related to cyclic AMP generation.
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Urine samples were collected from 200 subjects undergoing intravenous pyelography. The urine histamine levels were compared with those of 132 normal control subjects, 11 subjects with systemic mastocytosis, six subjects with idiopathic anaphylaxis, and ten subjects experiencing mild anaphylactic reactions during allergy immunotherapy. Compared with normal controls, as a group, all subjects receiving intravenous contrast media had increased urine histamine (P less than 0.05 by Student's t-test) while those subjects experiencing adverse reactions had considerably larger increases. The urine histamine levels in the subjects experiencing systemic reactions were in the same range as those observed in patients having mild anaphylactic reactions to immunotherapy and somewhat lower than those found in idiopathic anaphylaxis or systemic mastocytosis. These data suggest that some histamine release accompanies infusions of contrast media in all subjects and that larger amounts of histamine release are associated with adverse reactions.
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