Vaccine developments in AIDS : symposium

Meeting: International Conference on AIDS, 5th, 4-9 June, 1989, Montreal, QC, CAPresenters: Marc Girard, Scott Putney, Daniel Zagury, Clifford LaneSome dialogue in Frenc

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 contraction of the rat isolated portal vein was studied. 2. The isolated portal vein exhibited spontaneous phasic contractions. Removal of Ca(2+) from Krebs-Ringer solution or application of nifedipine abolished the spontaneous contraction, indicating that the contraction depends exclusively on Ca(2+) influx through L-type Ca(2+) channels. On the other hand, cyclopiazonic acid (CPA), a specific inhibitor of Ca(2+)-ATPase of sarcoplasmic reticulum (SR) increased the amplitude of the contractions, suggesting that the SR regulates the spontaneous contractions negatively by sequestration of Ca(2+) entering through L-type Ca(2+) channels and buffering the rise in cytosolic Ca(2+). 3. PGE(1) increased the amplitude of the spontaneous contraction in a concentration-dependent manner without affecting the resting tension. The effect was completely abolished 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 μM, Bay K 8644 at 100 nM and PE at 30 nM doubled the amplitude, respectively. 4. Pretreatment with 1 μM CPA abolished the effect of PGE(1), but the effects of Bay K 8644 and PE were not inhibited by pretreatment with CPA. In contrast, 10 μM ryanodine attenuated the effect of PE without affecting the contractile effect of PGE(1). 5. When the SR was depleted of Ca(2+) by repeated applications of caffeine in a nominally Ca(2+)-free Krebs-Ringer solution, it took about 120 s to restore the spontaneous contraction after addition of Ca(2+) into the solution. In CPA-treated veins, the time taken to restore the contraction was shortened significantly. Pretreatment with 1 μM PGE(1) shortened the time to the same extent as pretreatment with CPA did. 6. These results suggest that PGE(1) increases the amplitude of the spontaneous phasic contraction by a different mechanism from those by which PE and Bay K 8644 increase it. Inhibition of Ca(2+)-ATPase of the SR might be involved in the vasoactive effect of PGE(1)