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.