PROSTAGLANDIN-E2 CONTRACTS VASCULAR SMOOTH-MUSCLE AND INHIBITS POTASSIUM CURRENTS IN VASCULAR SMOOTH-MUSCLE CELLS OF RAT TAIL ARTERY

There is evidence to suggest that PGE(2) plays an important role in th e regulation of vascular smooth muscle tone. To determine the cellular basis of this action, we studied the effect of PGE(2) on force in hel ical muscle strips from rat tail artery. PGE(2) evoked a sustained con tractile response. The contractile response was concentration-dependen t, with an EC(50) value of 9.6 mu M. Patch-clamp studies were conducte d to investigate the effects of PGE(2) on K channels in isolated vascu lar smooth muscle cells from rat tail artery. Current-clamp studies sh owed that PGE(2) (1 mu M) depolarized the membrane by 15.9 +/- 1.3 mV. Under voltage-clamp conditions, a voltage-dependent, delayed outward rectifier K current was generated by stepwise depolarization from a ho lding potential of -80 mV. The current, which was activated at -45 to -40 mV and showed almost no inactivation, was inhibited by 45% using 1 0 mM TEA. PGE(2) inhibited the outward K current in a concentration-de pendent manner, with EC(50) values of 3.5 mu M and 4.9 mu M in primary and subcultured cells, respectively. The PGE(2) receptor antagonist s odium meclofenamate abolished the PGE(2)-induced K current inhibition. Furthermore, the intracellular application of guanosine 5'-O-[2-thiod iphosphate] (GDP beta S), a G protein inhibitor, and pretreatment of t he cells with cholera toxin prevented the PGE(2)-induced inhibition, w hereas application of pertussis toxin did not. These results suggest t hat PGE(2) modulates voltage-dependent delayed rectifier potassium cha nnels in VSMCs from rat tail artery via a receptor-mediated process in volving the activation of cholera toxin-sensitive and/or pertussis tox in-insensitive G protein(s).