Locus of action of Ni 2+ on histamine-induced inositol phosphate formation in brain slices and in HeLa cells

Abstract

Histamine-induced [ 3H]inositol monophosphate ([ 3H]IP 1) accumulation in slices of rat cerebral cortex and guinea-pig cerebral cortex and cerebellum was inhibited in a concentration-dependent manner by Ni 2+ ions. The effect of Ni 2+ 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 Ni 2+ of the binding of [ 3H]mepyramine had the characteristics expected for an allosteric inhibitor at the histamine H 1 receptor. Ni 2+ had no effect on carbachol-induced [ 3H]IP 1 formation in HeLa cells, but displaced the concentration-response curve for histamine to the right. The evidence suggests that Ni 2+ can act at two sites to block histamine-induced [ 3H]IP 1 accumulation in brain slices; at the level of the H 1 receptor and on a probable Ca 2+ entry component. In HeLa cells only the direct H 1 receptor action is evident.