Identification of ascorbic acid as the heat-stable factor from brain which inactivates the phorbol ester receptor.
Homogenates of calf cortex contained a heat-stable, low-molecular-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.
D000818:Animals; D001205:Ascorbic Acid / Q000302:isolation & purification* / Q000494:pharmacology; D001923:Brain Chemistry; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002417:Cattle; D005609:Free Radicals; D006358:Hot Temperature; D008054:Lipid Peroxides / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism; D011493:Protein Kinase C; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D005609:Free Radicals; D008054:Lipid Peroxides; D008563:Membrane Lipids; D010703:Phorbol Esters; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D001205:Ascorbic Acid