Phorbol esters inhibit agonist-induced [3H] inositol-1-phosphate accumulation in rat hippocampal slices.
In rat hippocampal slices, carbachol and norepinephrine induce an accumulation of [3H]-inositol-1-phosphate which is markedly amplified in the presence of lithium. The tumor-promoting agents phorbol 12,13-dibutyrate (PDB) and 4 beta phorbol, 12 beta-myristate, 13 alpha-acetate (PMA) have no effect on [3H] inositol-1-phosphate accumulation alone, but when preincubated with hippocampal slices significantly inhibit the accumulation of [3H]-inositol-1-phosphate induced by carbachol and norepinephrine. The IC50 values for PDB and PMA are 0.2 microM and 25 microM respectively. In contrast, the weak tumor promoting agents 4-O-methylphorbol 12 myristate 13 acetate (MPMA) and phorbol 13,20-diacetate (P 13,20 DA) only slightly attenuate the agonist-induced response at concentrations less than or equal to 100 microM, whereas 4 alpha-phorbol (4 alpha-PHR), a biologically inactive phorbol, has no effect. These data suggest that phorbol ester receptor-mediated events may be negatively coupled to agonist-induced phosphatidylinositol hydrolysis.
D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002217:Carbachol / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002352:Carrier Proteins; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007294:Inositol / Q000031:analogs & derivatives* / Q000378:metabolism; D007295:Inositol Phosphates; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C; D051381:Rats; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D007295:Inositol Phosphates; D010703:Phorbol Esters; D010704:Phorbols; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; C002647:inositol 1-phosphate; D015240:Phorbol 12,13-Dibutyrate; C043061:phorbol 13,20-diacetate; D007294:Inositol; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D002217:Carbachol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine; C033085:phorbol