Phorbol amplification of serotonin-induced arterial contractions is endothelium dependent.
This study determined the effect of phorbol pretreatment on serotonin [5-hydroxytryptamine (5-HT)]-induced contractions of rabbit abdominal aorta. Rings of aorta pretreated with 12-O-tetradecanoylphorbol 13-acetate (TPA, 10(-7) M) contracted more strongly (P less than 0.01) than rings pretreated with the vehicle dimethyl sulfoxide (0.0007%), but only at low 5-HT concentrations (10(-8) to 10(-7) M). A 10-min exposure to TPA (10(-7) M) increased (P less than 0.01) 5-HT contractions (10(-7) M) from 23.7 +/- 2.6 to 42.1 +/- 4.5%. This amplification required an intact endothelium and the use of a biologically active phorbol. Pretreatment with TPA (10(-7) M) reduced (P less than 0.01) acetylcholine-induced relaxations from 56.6 +/- 6.6 to 20.0 +/- 13.8%. Changes in guanosine 3',5'-cyclic monophosphate-mediated relaxation are not involved in this decrease, since relaxations to sodium nitroprusside (10(-9) to 10(-8) M) were not altered by TPA pretreatment. These results suggest that activation of protein kinase C in endothelial cells may produce arterial supersensitivity to 5-HT by decreasing the release of endothelium-derived relaxing factor(s) and/or by increasing the release of endothelium-derived contracting factor(s).
Consigny
P M
PM
Department of Physiology, Medical College of Pennsylvania, Philadelphia 19129.
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D009599:Nitroprusside; D009569:Nitric Oxide; D012701:Serotonin; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate