Interference of phorbolesters with endothelium-dependent vascular smooth muscle relaxation.
Histamine-induced endothelium-dependent relaxation (EDR) in the pulmonary artery was inhibited in a concentration-dependent manner by the phorbolester phorbol 12,13-dibutyrate (PDBu) (IC50: 70 nM) whereas EDR occurring in response to ionophore A 23187 was not affected by PDBu. The phorbolester 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), which does not activate protein kinase C (PKC), was without effect on receptor- or ionophore-induced EDR. The observed inhibition of signal transduction by PKC activation is suggested to reflect phosphorylation of the GTP binding protein Ni.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004727:Endothelium / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010703:Phorbol Esters / Q000494:pharmacology*
D010703:Phorbol Esters; D000001:Calcimycin; D006632:Histamine