Ca2(+)-mobilizing hormones stimulate Ca2+ efflux from hepatocytes.
Treatment of hepatocytes with 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a novel mobilizer of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool, produces a sustained elevation of [Ca2+]i (Kass, G. E. N., Duddy, S. K., and Orrenius, S. (1989) J. Biol. Chem. 264, 15192-15198). Exposure of hepatocytes to the Ca2(+)-mobilizing hormones, vasopressin, angiotensin II, or ATP following [Ca2+]i elevation by tBuBHQ produced a rapid return of [Ca2+]i to basal or near basal levels. Release of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool by tBuBHQ following pretreatment with vasopressin or angiotensin II resulted in a [Ca2+]i transient and not the sustained [Ca2+]i elevation observed in the absence of the Ca2(+)-mobilizing hormones. The G-protein activator, NaF plus AlCl3, mimicked both effects of the Ca2(+)-mobilizing hormones on [Ca2+]i. The mechanism for Ca2+ removal from the cytosol by Ca2(+)-mobilizing hormones did not involve cyclic nucleotides nor did it require protein kinase C activation or cyclo- and lipoxygenase-dependent metabolites of arachidonic acid. Furthermore, the hormone-mediated decrease in [Ca2+]i did not involve the pertussis toxin-sensitive Gi-protein. Removal of the tBuBHQ-mobilized Ca2+ from the cytosol of hepatocytes by Ca2(+)-mobilizing hormones was mediated by stimulation of a Ca2+ efflux pathway. Thus, in addition to initiating [Ca2+]i transients by releasing Ca2+ from the inositol 1,4,5-trisphosphate-sensitive Ca2+ store and stimulating Ca2+ influx, Ca2(+)-mobilizing hormones also regulate the termination of the [Ca2+]i transient by stimulating a Ca2+ efflux pathway.
Duddy
S K
SK
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Kass
G E
GE
Orrenius
S
S
D000818:Animals; D001572:Benzofurans; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006873:Hydroquinones / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001572:Benzofurans; D005456:Fluorescent Dyes; D006873:Hydroquinones; D007093:Imidazoles; D010566:Virulence Factors, Bordetella; D014667:Vasopressins; C019359:2,5-di-tert-butylhydroquinone; D003995:Dibutyryl Cyclic GMP; C031938:calmidazolium; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D003994:Bucladesine; D014700:Verapamil; D037342:Pertussis Toxin; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016257:Fura-2