Homogenates of calf cortex contained a heat-stable, lowmolecular-weight factor which inhibited in a dose-dependent, irreversible, and noncompetitive manner the binding of [20-3H]phorbol-12,13-dibutyrate to its receptor in brain particulate preparations. The inhibitory factor was identified as ascorbic acid. As in other cases in which ascorbic acid alters the activity of membrane proteins, inactivation of phorbol ester binding by ascorbic acid was not stereospecific, correlated with stimulation of lipid peroxidation, and could be blocked by inhibitors of lipid peroxidation. Free radical-mediated receptor inactivation could potentially play a role in systems in which phorbol esters stimulate the generation of active oxygen species or fatty acid hydroperoxides. In addition, protection of the [20-3H]phorbol-12,13-dibutyrate receptor from free radical damage would be desirable in the screening of extracts for competitive inhibitory activities.

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Supported by Grant CA 22895 from the NIH.

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