Effects of a phorbol ester on rat aortic contraction and calcium influx in the presence and absence of BAY k 8644.
Phorbol esters like phorbol-12,13-dibutyrate (PDB) exert potent contractile effects on rat aorta. In the present study, we determined whether phorbol esters alter contraction by augmenting calcium influx through calcium channels. Isometric tensions and calcium influx (using 45Ca) were measured in rat aortic rings exposed to PDB in the presence and absence of BAY k 8644, a calcium channel agonist. We found that PDB alone caused significant increases in isometric tension. The addition of 100 nM BAY k 8644 enhanced the PDB-induced rat aortic contraction which was inhibited as well as reversed by the calcium channel antagonist, nitrendipine. In the presence of PDB alone, calcium influx was significantly increased only after an extended time (30 min) of isometric contraction. In the presence of BAY k 8644, however, PDB caused a significant increase in calcium influx during shorter periods (10 min) of isometric contraction. We also found that the biologically inactive phorbol, 4-alpha-phorbol, did not potentiate the effects of BAY k 8644 on either contraction or calcium influx. These results indicate that PDB may induce rat aortic contraction via activation of protein kinase C which in the presence of a calcium channel agonist can potentiate the mobilization of calcium through nitrendipine-sensitive calcium channels.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists; D004347:Drug Interactions; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
D002120:Calcium Channel Agonists; D007473:Ion Channels; D010703:Phorbol Esters; D015240:Phorbol 12,13-Dibutyrate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D011493:Protein Kinase C; D002118:Calcium