HISTAMINE STIMULATION OF INOSITOL 1-PHOSPHATE ACCUMULATION IN LITHIUM-TREATED SLICES FROM REGIONS OF GUINEA-PIG BRAIN

Histamine stimulated the accumulation of [3H]inositol 1-phosphate in the presence of 10 mM LiCl in [3H]inositol-loaded tissue slices from several regions of guinea pig brain. The level of [3H]inositol 1-phosphate increased approximately linearly, after an initial lag period, up to a time of 120 min. In the absence of Li+ the accumulation of the 1-phosphate stimulated by histamine in cerebral cortical and hippocampal slices was markedly reduced. Li+ had much less effect on the response to histamine in cerebellar slices. The characteristics of the response to histamine were consistent with mediation by H1 receptors, and the affinity constants derived for mepyramine (2.3 .times. 109 M-1) and methapyrilene (1.8 .times. 108 M-1) were similar to those reported from measurements on other H1 responses in the guinea pig. The EC50 [mean effective concentration] for histamine was similar in cerebellum, cerebral cortex, hippocampus and hypothalamus. The position of the dose-response curve for histamine in cerebral cortical slices was similar to that of the curve for the receptor binding of histamine deduced from histamine inhibition of [3H]mepyramine binding.