title: Histamine-H1-receptor-mediated phosphoinositide hydrolysis, Ca2+ signalling and membrane-potential oscillations in human HeLa carcinoma cells.
abstract: In human HeLa carcinoma cells, histamine causes a dose-dependent formation of inositol phosphates, production of diacylglycerol and a transient rise in intracellular [Ca2+]. These responses are completely blocked by the H1-receptor antagonist pyrilamine. In streptolysin-O-permeabilized cells, formation of inositol phosphates by histamine is strongly potentiated by guanosine 5'-[gamma-thio]triphosphate and inhibited by guanosine 5'-[beta-thio]diphosphate, suggesting the involvement of a GTP-binding protein. Histamine stimulates the rapid but transient formation of Ins(1,4,5)P3, Ins(1,3,4)P3 and InsP4. InsP accumulates in a much more persistent manner, lasting for at least 30 min. Studies with streptolysin-O-permeabilized cells indicate that InsP accumulation results from dephosphorylation of Ins(1,4,5)P3, rather than direct hydrolysis of PtdIns. The rise in intracellular [Ca2+] is biphasic, with a very fast release of Ca2+ from intracellular stores, that parallels the Ins(1,4,5)P3 time course, followed by a more prolonged phase of Ca2+ influx. In individual cells, histamine causes a rapid initial hyperpolarization of the plasma membrane, which can be mimicked by microinjected Ins(1,4,5)P3. Histamine-induced hyperpolarization is followed by long-lasting oscillations in membrane potential, apparently owing to periodic activation of Ca2+-dependent K+ channels. These membrane-potential oscillations can be mimicked by microinjection of guanosine 5'-[gamma-thio]triphosphate, but are not observed after microinjection of Ins(1,4,5)P3. We conclude that H1-receptors in HeLa cells activate a PtdInsP2-specific phospholipase C through participation of a specific G-protein, resulting in long-lasting oscillations of cytoplasmic free Ca2+.
authors.affiliation: Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
authors.forename: B C
authors.initials: BC
authors.lastname: Tilly
authors.forename: L G
authors.initials: LG
authors.lastname: Tertoolen
authors.forename: A C
authors.initials: AC
authors.lastname: Lambrechts
authors.forename: R
authors.initials: R
authors.lastname: Remorie
authors.forename: S W
authors.initials: SW
authors.lastname: de Laat
authors.forename: W H
authors.initials: WH
authors.lastname: Moolenaar
mesh_terms: D000535:Aluminum / Q000494:pharmacology; D017607:Aluminum Compounds; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005459:Fluorides / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006367:HeLa Cells; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008564:Membrane Potentials; D010507:Periodicity; D010716:Phosphatidylinositols / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000502:physiology*; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D004075:Diglycerides; D010716:Phosphatidylinositols; D015221:Potassium Channels; D011969:Receptors, Histamine H1; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006632:Histamine; D006160:Guanosine Triphosphate; D000535:Aluminum; D010738:Type C Phospholipases; D005459:Fluorides; D002118:Calcium; C032311:aluminum fluoride