Rapid changes in intracellular Zn2+ in rat hepatocytes.
Changes in the concentration of free Zn2+ were monitored in isolated rat hepatocytes using the fluorescent indicator zinquin (ethyl[2-methyl-8-p-toluenesulphonamido-6-quinolyloxy]acetat e). The concentration of Zn2+ in freshly isolated hepatocytes was 1.3 x 10(-6) M (range 0.61-2.7 x 10[-6] M). This value decreased by about 10%-15% during incubation in the absence of zinc and increased in a time- and concentration-dependent manner in the presence of exogenous zinc (Km approximately 10 microM). IIb group metal ions led to a concentration-dependent increase in zinquin fluorescence. The rank of efficacy was Hg approximately Cd > Pb (IVa) >> Cu (Ib) >>> Ni (VIII). This rank resembles their ability to mobilize zinc from metallothioneins. 8-Br-3',5'-cAMP (10[-4]M) caused a rapid decrease in Zn2+ epifluorescence which was apparent within 10 min and was sustained throughout the experiment. This effect was gradually obliterated in the presence of external ZnCl2. The effect was specific for cAMP (or cAMP generating hormones) as the calcium-dependent hormone [arg8]vasopressin (5 x 10[-8] M) did not affect intracellular Zn2+. An integrated role of zinc as a possible mediator in signal transduction is discussed.
Kleineke
J W
JW
Abteilung Klinische Biochemie, Zentrum Innere Medizin Universität Göttingen, Germany. jkleine2@gwdg.de
Brand
I A
IA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D006490:Hemostatics / Q000494:pharmacology; D007854:Lead / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008628:Mercury / Q000494:pharmacology; D008668:Metallothionein / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D015363:Quinolones; D051381:Rats; D014105:Tosyl Compounds; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology; D017967:Zinc Compounds / Q000494:pharmacology
D002712:Chlorides; D005456:Fluorescent Dyes; D006490:Hemostatics; D015363:Quinolones; D014105:Tosyl Compounds; D017967:Zinc Compounds; D002104:Cadmium; D001127:Arginine Vasopressin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007854:Lead; D003300:Copper; D009532:Nickel; C016837:zinc chloride; D008668:Metallothionein; D008628:Mercury; D015032:Zinc; C084731:zinquin