TY - JOUR T1 - Inhibition of brain protein kinase C subtypes by lead. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 757 LP - 761 VL - 264 IS - 2 AU - K Murakami AU - G Feng AU - S G Chen Y1 - 1993/02/01 UR - http://jpet.aspetjournals.org/content/264/2/757.abstract N2 - Protein kinase C (PKC) is an important enzyme in mediating cellular signal transduction and neuronal plasticity. Extremely low concentrations (picomolar range) of Pb++ have been reported to activate partially purified PKC from rat brain (Markovac and Goldstein, 1988). However, the lead activation of PKC at such low concentrations is still a matter of discussion (Simons, 1989). To clarify this point, we have examined the lead effect on highly purified PKC subtypes. Pb++ was found to be a potent inhibitor for all three PKC subtypes (types I, II and III) with IC50 of 2 to 10 microM. Characterization of this lead inhibition of PKC suggests that 1) the inhibition is not due to the competition with Ca++, 2) the site of action of lead is on the catalytic domain of PKC, 3) the inhibition is not dependent on the mode of activation (phosphatidylserine/diacylglycerol vs. cis-unsaturated fatty acid) and 4) the inhibition is totally reversible. ER -