ABSTRACT
In the presence of endothelial cells, prostacyclin and iloprost induced a concentrationdependent hyperpolarization of the smooth muscle cells. The hyperpolarization pro duced by iloprost was significantly larger than the one produced by prostacyclin. In presence of Bay U3405, the responses to iloprost were unaffected while those to prostacyclin were increased significantly with a shift to the left of the concentrationresponse curve. The metabolite of prostacyclin, 6-ke toPGFi Q did not affect the membrane potential of the smooth muscle cells while U46619 and prostaglandin F2 Q produced a significant, sustained and stable depolarization. Glibenclamide abolished the hyper polarization induced by iloprost. In contrast, the response to prostacyclin was either unaffected, converted to depolarization or converted to slow wave activity with firing of action potentials. In the presence of the association of glibenclamide, charybdotoxin and apamin, prostacyclin produced only depolarization. The electrical changes induced by prostacyclin, in the presence of glibenclamide were abolished by Bay U3405. After removal of the endothelium, iloprost and prostacyclin produced hyperpolarizations that were not significantly different from those observed in controls. The concentrationresponse curve to prostacyclin was still significantly enhanced and shifted in the presence of Bay U3405. However, in the presence of glibenclamide, prostacyclin produced only a depolarization that was abolished by Bay U3405. These results indicate that in the carotid artery of the guinea-pig, iloprost activate IP receptor on the smooth muscle cells and produce hyperpolarization by the opening of ATP-sensitive potassium channels. In contrast, prostacyclin (or one of its metabolite different from 6-ketoPGF] a ) can produce additional endothelium-dependent and independent effects that are sensitive to Bay U3405. In the absence of the endothelium, the activation of TP-receptors produces depolarization and partially antagonizes the hyperpolarization mediated by IP receptors. In the presence of the endothelial lining, the changes in membrane potential produced by prostacyclin involve the activation of calcium-activated potassium channels. Whether or not this endothelial effect involves the release of an unidentified factor or myo-endothelial gap junctions remains uncertain.
