Histamine-elicited accumulations of cyclic adenosine 3',5'-monophosphate in guinea-pig brain slices: effect of H1- and H2-antagonists

Rogers, M.; Dismukes, K.; Daly, J.W.

Journal of Neurochemistry 25(4): 531-534

1975


ISSN/ISBN: 0022-3042
PMID: 239099
DOI: 10.1111/j.1471-4159.1975.tb04361.x
Accession: 068525026

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Abstract
In guinea-pig hippocampal slices, both metiamide and D-brompheniramine at a concentration of 10 .mu.M-inhibited histamine-elicited formation of [14C]cyclic AMP by about 50%. The combination of 5 .mu.M-metiamide and 5 .mu.M-D-brompheniramine produced significantly more inhibition than did either 10 .mu.M-metiamide or 10 .mu.M-D-brompheniramine alone, indicating that the antagonists are, indeed, acting at separate receptor systems. When concentration of the H1- and H2-antagonists were increased to 100 .mu.M, metiamide now caused significantly more inhibition of the histamine-response than did D-brompheniramine. At 1000 .mu.M, both metiamide and D-bromopheniramine almost completely blocked the response to histamine. The H1-antagonists, chlorpheniramine, promethazine, thephorin and pyrilamine at 10 .mu.M, inhibited the histamine response by 50-74%, suggesting an affinity for receptors between D- and L-brompheniramine. Burimamide at 1 .mu.M had no effect on histamine response in neocortical slices. Both H1- and H2-receptors are associated with histamine-elicited accumulations of cyclic AMP in guinea-pig hippocampal slices. Nearly 1/2 of the histamine-response in this brain region is due to H2-receptor mechanisms. In view of the partial nonselectivity of the H1- and H2-antagonists revealed at the very high concentration of 1000 .mu.M, no precise assessment of the relative importance of the 2 receptor-type is possible. The histamine-receptors in hippocampus differ significantly from those in neocortex.