LOCUS OF ACTION OF NI2+ ON HISTAMINE-INDUCED INOSITOL PHOSPHATE FORMATION IN BRAIN-SLICES AND IN HELA-CELLS

Histamine-induced [H-3]inositol monophosphate ([H-3]IP1) accumulation in slices of rat cerebral cortex and guinea-pig cerebral cortex and cerebellum was inhibited in a concentration-dependent manner by Ni2+ ions. The effect of Ni2+ on the concentration-response curve for histamine in rat cerebral cortex was consistent with non-competitive inhibition. In membranes from guinea-pig cerebral cortex inhibition by Ni2+ of the binding of [H-3]mepyramine had the characteristics expected for an allosteric inhibitor at the histamine H-1 receptor. Ni2+ had no effect on carbachol-induced [H-3]IP1 formation in HeLa cells, but displaced the concentration-response curve for histamine to the right. The evidence suggests that Ni2+ can act at two sites to block histamine-induced [H-3]IP1 accumulation in brain slices; at the level of the H, receptor and on a probable Ca2+ entry component. In HeLa cells only the direct H-1 receptor action is evident.