Contrasting effects of phorbol dibutyrate and phorbol myristate acetate in rabbit aorta.
In rat hepatocytes, active phorbol esters inhibited the alpha 1-adrenergic stimulation of phosphatidylinositol labeling with the expected potency order: phorbol myristate acetate (PMA) greater than phorbol dibutyrate (PDB). In contrast, in rabbit aorta the alpha 1-adrenergic action was inhibited dose-dependently by PDB but not by PMA. Similarly PDB (but not PMA) induced a strong contraction in rabbit aorta. The phorbol ester-induced contraction developed slowly, was dose-dependent and independent of extracellular calcium. These effects of PDB in rabbit aorta were neither inhibited by the protein kinase inhibitor H-7 nor mimicked by the synthetic diacylglycerol, OAG. Our results raise some doubts on the mechanism(s) through which the actions of PDB take place in rabbit aorta.
Depto. de Farmacología, CINVESTAV-IPN, Mexico, D.F.
R
R
Villalobos-Molina
V
V
Ransanz
M E
ME
Torres-Márquez
E
E
Hong
J A
JA
García-Sáinz
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007546:Isoquinolines; D010710:Phosphates; D010716:Phosphatidylinositols; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine