Effect of phthalazinol (EG-626) on the mechanical activity and calcium influx of rabbit portal vein (1).
Phthalazinol (EG-626), a newly synthesized cyclic AMP phosphodiesterase inhibitor, inhibited spontaneous phasic contractions (SPC) of isolated rabbit portal veins in a dose-dependent manner. Phthalazinol at a minimal concentration necessary to completely abolish the SPC did not alter 45Ca-uptake, 45Ca-influx, or the ED50S for methoxamine (me) and K+, but it did reduce the amplitude of the tonic contractions induced by ME and K+ by approximately 25%. On the other hand, verapamil, and La+3 abolished SPC, ME, and K+-induced contractions. Tetrodotoxin had no effect on SPC or on tonic contractions induced by ME and K+. Since extracellular Ca++ is known to be essential for SPC, ME, and K+-induced contractions in rabbit portal vein, the present results suggest that the abolishment of SPC and the partial inhibition of the ME and K+ responses by phthalazinol may be related to an action of this agent on intracellular Ca++ or Ca++-efflux.
D000818:Animals; D001769:Blood / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010793:Phthalazines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology
D002132:Calcium Radioisotopes; D010793:Phthalazines; D011724:Pyridazines; C011329:phthalazinol; D007811:Lanthanum; D014700:Verapamil; D008729:Methoxamine; D011188:Potassium; D002118:Calcium