Antagonism of concanavalin A capping in phorbol ester-activated lymphocytes by calmodulin inhibitors and certain amino acid esters.
12-O-Tetradecanoylphorbol-13-acetate (TPA), an effective tumor promoter in mouse skin and comitogen in bovine lymphocytes, rapidly stimulates concanavalin A-mediated cap formation in the latter cells. The ability of different phorbol derivatives to facilitate the capping reaction correlates well with their potencies as lymphocyte comitogens and as tumor-promoting agents. This effect of TPA on capping in bovine lymphocytes, which is apparent within min, is neither mimicked nor altered by dibutyryl cyclic adenosine 3':5'-monophosphate or cyclic guanosine 3':5'-monophosphate. Cytochalasin D, a microfilament-disrupting agent, inhibits cap formation, thereby suggesting the participation of microfilaments in the response. Benzoyl tyrosine ethyl ester selectively inhibits the TPA-stimulated cap formation, whereas benzoyl tyrosinamide is inactive. A comparison of related amino acid derivatives reveals that their activities are dependent on the nature of both the amino acid side chain and the carboxyl end blocking group. Trifluoperazine and N-(6-aminohexyl)-5-chloronaphthalenesulfonamide, known inhibitors of the calmodulin-dependent processes, also selectively block the TPA-stimulated cap formation, whereas trifluoperazine sulfoxide, a less effective calmodulin antagonist, is relatively inactive. These data suggest that the stimulation of capping by TPA involves the activation of a calmodulin-dependent process which may also be regulated by the function of an esterase.
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002417:Cattle; D003208:Concanavalin A / Q000494:pharmacology*; D003571:Cytochalasin B / Q000494:pharmacology; D015638:Cytochalasin D; D003572:Cytochalasins / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000276:immunology; D004952:Esters; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D010703:Phorbol Esters / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000596:Amino Acids; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D003572:Cytochalasins; D004952:Esters; D010703:Phorbol Esters; D010704:Phorbols; D003208:Concanavalin A; D015638:Cytochalasin D; D003571:Cytochalasin B; D013755:Tetradecanoylphorbol Acetate