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  • Title: Locus of action of Ni2+ on histamine-induced inositol phosphate formation in brain slices and in HeLa cells.
    Author: Arias-Montaño JA, Young JM.
    Journal: Eur J Pharmacol; 1993 May 15; 245(3):221-8. PubMed ID: 8335060.
    Abstract:
    Histamine-induced [3H]inositol monophosphate ([3H]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 [3H]mepyramine had the characteristics expected for an allosteric inhibitor at the histamine H1 receptor. Ni2+ had no effect on carbachol-induced [3H]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 [3H]IP1 accumulation in brain slices; at the level of the H1 receptor and on a probable Ca2+ entry component. In HeLa cells only the direct H1 receptor action is evident.
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