Locus of action of Ni2+ on histamine-induced inositol phosphate formation in brain slices and in HeLa cells.
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.
Arias-Montaño
J A
JA
Department of Pharmacology, University of Cambridge, UK.
Young
J M
JM
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006367:HeLa Cells; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011738:Pyrilamine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011968:Receptors, Histamine / Q000187:drug effects* / Q000378:metabolism
D007295:Inositol Phosphates; D011968:Receptors, Histamine; D010643:Phenoxybenzamine; C002647:inositol 1-phosphate; D009532:Nickel; D006632:Histamine; D002217:Carbachol; D011738:Pyrilamine