Phorbol 12,13-dibutyrate enhances lateral redistribution of membrane glycoproteins in human blood lymphocytes.
Nanomolar concentrations of 4 beta-phorbol 12,13-dibutyrate markedly enhanced the redistribution of concanavalin A receptors, the common leukocyte antigen and the Lyt-3 antigen in human blood lymphocytes, as measured by cap formation. The effect on the lateral mobility of these cell surface molecules was dose dependent and occurred within a few minutes of treatment. 12-O-Tetradecanoyl phorbol 13-acetate, another tumor promoter, was similarly active. 4 alpha-Phorbol 12,13-didecanoate, which does not have tumor-promoting activity, did not enhance cap formation. The effect of various drugs and treatments indicated that the phorbol ester-enhanced cap formation was energy and temperature dependent and required functional microfilaments. Retinoic acid, an antitumor-promoting agent, was inhibitory and trifluoperazine, an inhibitor of calmodulin-dependent processes, had a minor inhibitory effect. Protein secretion and synthesis, extracellular Ca2+/Mg2+ and functional microtubules did not seem to be involved. The enhanced capping was inhibited by the alkylating agents tosyl phenylalanyl chloromethyl ketone and tosyl lysyl chloromethyl ketone but not by other protease inhibitors. The effect of various amino acid derivatives suggested the participation of an esterase. A comparative study of dose response, kinetics and sensitivity to drugs indicated a direct correlation between the phorbol 12,13-dibutyrate-enhanced redistribution of membrane glycoconjugates and the phorbol ester-induced binding (adhesion) between human blood lymphocytes, a phenomenon previously described.
D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007152:Immunologic Capping / Q000187:drug effects*; D008214:Lymphocytes / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006023:Glycoproteins; D008565:Membrane Proteins; D010703:Phorbol Esters; D010704:Phorbols; D011480:Protease Inhibitors; D015240:Phorbol 12,13-Dibutyrate; D013755:Tetradecanoylphorbol Acetate