8-isoprostaglandin E(2) activates Ca(2+)-dependent K(+) current via cyclic AMP signaling pathway in murine renal artery.
The inhibitory pathway of 8-isoprostaglandin E(2) was investigated in murine renal arterial smooth muscle. K(+) current was augmented in a concentration-dependent fashion, with an average increase of 123+/-28% (n=6) following application of 10(-5) M 8-iso PGE(2). This augmentation was observed in the presence of 4-aminopyridine (4-AP, 10(-3) M) but not that of charybdotoxin (Ch Tx, 10(-7) M). Fluorimetric recordings showed marked concentration-dependent increase of cytosolic Ca(2+) levels by 8-iso PGE(2), while an enzyme-linked immunosorbent assay (ELISA)-based cyclic AMP assay showed increased cAMP levels by 10(-7) M 8-iso PGE(2) challenge. The isoprostane-induced augmentation was prevented by the ryanodine receptor blocker ruthenium red (10(-5) M) or the adenylate cyclase blocker SQ 22536 (10(-4) M). The protein kinase A (PKA) inhibitor H 89 (10(-5) M) inhibited resting K(+) currents (78+/-5%, n=5) but did not prevent 8-iso PGE(2) from augmenting the remaining K(+) current. We conclude that 8-iso PGE(2) enhances Ca(2+)-dependent K(+) currents in murine renal artery through a cAMP-dependent pathway which may involve internally sequestered Ca(2+).
Zhang
Yongde
Y
Department of Medicine, McMaster University, Firestone Institute of Respiratory Health, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, Ontario, Canada, L8N 4A6.
Pertens
Evi
E
Janssen
Luke J
LJ
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001685:Biological Factors; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D028421:Isoprostanes / Q000494:pharmacology*; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction
D000067956:Adenylyl Cyclase Inhibitors; D001685:Biological Factors; D028421:Isoprostanes; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D047428:Protein Kinase Inhibitors; C067410:endothelium-dependent hyperpolarization factor; C017759:9-(tetrahydro-2-furyl)-adenine; D000242:Cyclic AMP; D000225:Adenine; D015232:Dinoprostone; D011188:Potassium; D002118:Calcium; C011987:8-isoprostaglandin E2