THE MECHANISM OF CONTRACTILE EFFECTS OF OUABAIN AND ZINC ON THE RAT UTERUS

¹ Departments of Pharmacology, St. Mary's Hospital Medical School, Paddington, London, England; The University of Alberta, Edmonton, Canada

We tested the postulate that inhibition of transport adenosine triphosphatase in uteri from estrogen-treated rats caused contractions of the myometrium. Chelating agents such as 8-hydroxyquinoline (HQ) were shown to produce selective inhibition of ouabain-induced contraction without preventing ouabain-induced downhill ion movements—actions previously observed with epinephrine. Also, lower doses of ouabain (10^-4 M) potentiated submaximal contractions to a variety of agonists. Potentiation of contractions by ouabain was prevented selectively by epinephrine and HQ. Thus, potentiation of contractions from low doses of ouabain and contraction from higher doses seemed to occur by the same mechanism. Potentiating doses of ouabain, unlike doses causing contraction, did not cause downhill ion movements of Na, K, Ca or Mg, or accelerate uphill movements of these ions. Zinc ions (10^-4 M) also potentiated contractions to agonists, including ouabain, without causing downhill ion movements by a mechanism which may be similar to that of ouabain. These effects were also selectively inhibited by epinephrine and HQ. The mechanism of action of zinc and ouabain on contraction was not by inhibition of transport adenosine triphosphatase. It may involve an increase in activity of zinc ions inside a lipid barrier; water-soluble congeners of HQ and phenanthroline, such as 8-hydroxyquinoline sulfonate, did not inhibit ouabain contractions. Zinc ions partially prevented activation of phosphorylase by 3 x 10^-6 M epinephrine, but 10^-3 M ouabain did not. The possibility that adenylcyclase might be the site of action of zinc ions in the membrane is discussed.