PROSTAGLANDIN E-1 POTENTIATION OF THE SPONTANEOUS PHASIC CONTRACTION OF RAT ISOLATED PORTAL-VEIN BY A CYCLOPIAZONIC ACID-SENSITIVE MECHANISM

1 The effect of prostaglandin E-1 (PGE(1)) on the spontaneous phasic c ontraction of the rat isolated portal vein was studied. 2 The isolated portal vein exhibited spontaneous phasic contractions. Removal of Ca2 + from Krebs-Ringer solution or application of nifedipine abolished th e spontaneous contraction, indicating that the contraction depends exc lusively on Ca2+ influx through L-type Ca2+ channels. On the other han d, cyclopiazonic acid (CPA), a specific inhibitor of Ca2+-ATPase of sa rcoplasmic reticulum (SR) increased the amplitude of the contractions, suggesting that the SR regulates the spontaneous contractions negativ ely by sequestration of Ca2+ entering through L-type Ca2+ channels and buffering the rise in cytosolic Ca2+ 3 PGE(1) increased the amplitude of the spontaneous contraction in a concentration-dependent manner wi thout affecting the resting tension. The effect was completely abolish ed by nifedipine. Bay K 8644 and phenylephrine (PE) also increased the amplitude of the contraction in a concentration-dependent manner. PGE (1) at a concentration of 1 mu M, Bay K 8644 at 100 nM and PE at 30 nM doubled the amplitude, respectively. 4 Pretreatment with 1 mu M CPA a bolished the effect of PGE(1), but the effects of Bay K 8644 and PE we re not inhibited by pretreatment with CPA. In contrast, 10 mu M ryanod ine attenuated the effect of PE without affecting the contractile effe ct of PGE(1). 5 When the SR was depleted of Ca2+ by repeated applicati ons of caffeine in a nominally Ca2+-free Krebs-Ringer solution, it too k about 120 s to restore the spontaneous contraction after addition of Ca2+ into the solution. In CPA-treated veins, the time taken to resto re the contraction was shortened significantly. Pretreatment with 1 mu M PGE(1) shortened the time to the same extent as pretreatment with C PA did. 6 These results suggest that PGE(1) increases the amplitude of the spontaneous phasic contraction by a different mechanism from thos e by which PE and Bay K 8644 increase it. Inhibition of Ca2+-ATPase of the SR might be involved in the vasoactive effect of PGE(1).