2,5-Di(tert-butyl)-1,4-benzohydroquinone--a novel mobilizer of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool.
Isolated hepatocytes and the isolated perfused rat liver have been used to study the alterations of cytosolic free Ca2+ concentration ([Ca2+]i) produced by 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a potent inhibitor of hepatic microsomal Ca2+ sequestration (Moore, G.A., McConkey, D.J., Kass, G.E.N., O'Brien, P.J. and Orrenius, S. FEBS Lett., 224, 331-336), (1987). Addition of tBuBHQ to isolated hepatocytes caused a rapid increase in [Ca2+]i which was similar in magnitude to the [Ca2+]i elevation induced by the Ca2+ mobilizing hormone, vasopressin. In contrast with vasopressin which caused a Ca2+ transient, tBuBHQ elevated [Ca2+]i to a new steady state that was maintained for up to 15-20 min. When vasopressin was administered during the tBuBHQ-induced period of elevated [Ca2+]i, [Ca2+]i rapidly returned to basal levels. Similarly, if vasopressin was administered just prior to tBuBHQ, the resultant tBuBHQ-dependent change in [Ca2+]i was transient, and not sustained. The hydroquinone mobilized the same intracellular Ca2+ pool as inositol 1,4,5-trisphosphate, but tBuBHQ did not produce any detectable inositol polyphosphate accumulation. tBuBHQ stimulated glucose release from perifused hepatocytes, mimicking the effect of vasopressin. In the perfused liver, tBuBHQ infusion produced a single, slow and prolonged release of Ca2+ into the perfusate and inhibition of subsequent vasopressin-induced Ca2+ effluxes. Inhibition of the response to vasopressin was reversed over time, and closely correlated with the extent of inhibition of both Ca2+ sequestration and (Ca2+-Mg2+)-ATPase activity in microsomes isolated from the isolated perfused liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Moore
G A
GA
Department of Toxicology, Karolinska Institute, Stockholm, Sweden.
Kass
G E
GE
Duddy
S K
SK
Farrell
G C
GC
Llopis
J
J
Orrenius
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology*; D066298:In Vitro Techniques; D007292:Inosine Nucleotides / Q000494:pharmacology*; D007293:Inosine Triphosphate / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012503:Saponins / Q000494:pharmacology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology
D002132:Calcium Radioisotopes; D006873:Hydroquinones; D007292:Inosine Nucleotides; D008112:Liver Glycogen; D012503:Saponins; D014667:Vasopressins; D007293:Inosine Triphosphate; C019359:2,5-di-tert-butylhydroquinone; D002118:Calcium