title: Histamine-induced intracellular free Ca++, inositol phosphates and electrical changes in murine N1E-115 neuroblastoma cells.
abstract: Apparent intracellular free Ca++ concentration [(Ca++]i) was measured in differentiated N1E-115 neuroblastoma by microinjecting cells with aequorin (estimated intracellular concentration, 4 microM) and measuring light emission. Histamine produced a transient, dose-dependent increase in [Ca++]i. Pyrilamine blocked completely the response to histamine whereas cimetidine had no effect. Omitting Ca++ from the external medium reversibly blocked the response. As well as a rise in [Ca++]i, histamine caused a concomitant cell hyperpolarization that was not blocked by ouabain, low Cl-, tetraethylammonium chloride/tetradotoxin or metiamide but was blocked by apamin and pyrilamine. A secondary small depolarization caused by histamine was also blocked by apamin but not by ouabain, low Cl- or tetraethylammonium chloride/tetrodotoxin. Direct iontophoretic injection of Ca++ into cells caused only hyperpolarization. Injection of inositol 1,4,5-trisphosphate [IP3(1,4,5)] caused an increase in [Ca++]i and rapid hyperpolarization. Inositol 1,3,4-trisphosphate [IP3(1,3,4)] caused an increase in [Ca++]i, rapid hyperpolarization and a slower depolarization. Repeated injections of IP3(1,3,4) led to a diminished [Ca++]i response and decreased hyperpolarization but had no effect on depolarization. Inositol 1,3,4,5-tetrakisphosphate was without effect on [Ca++]i or on cellular membrane potential. The results suggest that histamine causes an H1 receptor-dependent increase in [Ca++]i, probably by the increased entry of extracellular Ca++, although there may be a contribution from intracellular Ca++ released by IP3(1,4,5). The increase in [Ca++]i activates K+ channels leading to cell hyperpolarization. IP3(1,3,4) formed from inositol 1,3,4,5-tetrakisphosphate, which is itself a product of IP3(1,4,5), causes a slower depolarization by a mechanism that does not involve Na+ channels or an increase in [Ca++]i.
authors.affiliation: Department of Pharmacology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: S G
authors.initials: SG
authors.lastname: Oakes
authors.forename: P A
authors.initials: PA
authors.lastname: Iaizzo
authors.forename: E
authors.initials: E
authors.lastname: Richelson
authors.forename: G
authors.initials: G
authors.lastname: Powis
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis* / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D009447:Neuroblastoma / Q000503:physiopathology; D015221:Potassium Channels / Q000187:drug effects; D013403:Sugar Phosphates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D002712:Chlorides; D007295:Inositol Phosphates; D015221:Potassium Channels; D013403:Sugar Phosphates; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium