| 16153635 |
Zhang Y, Pertens E, Janssen LJ: 8-isoprostaglandin E (2) activates Ca (2+)-dependent K (+) current via cyclic AMP signaling pathway in murine renal artery. Eur J Pharmacol. 2005 Sep 27;520(1-3):22-8.
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+). |
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