PGE2 inhibits basolateral 50 pS potassium channels in the thick ascending limb of the rat kidney.
To study the inhibition of the inwardly rectifying basolateral 50 pS potassium channels by PGE(2) we performed patch-clamp studies on the basolateral membrane of the rat kidney thick ascending limb. PGE(2)'s effect was mimicked by the selective EP1- and EP3-receptor agonist, sulprostone, but was prevented by inhibiting protein kinase-C with calphostin-C. The mitogen-activated protein kinase inhibitor PD98059 (ERK) or SB203580 (p38) increased basal channel activity; however, while neither alone prevented the inhibitory effect of PGE(2), but using both of them together completely abolished PGE(2)'s effect on channel activity. Treatment with PGE(2) stimulated phosphorylation of both p38 and ERK in primary cultures of medullary thick ascending limb cells. The PGE(2)-mediated mitogen-activated protein kinase activation was not affected by indomethacin, but was completely blocked by calphostin-C. These studies show that inhibition of basolateral 50 pS potassium channels by PGE(2) is mediated by protein kinase-C, which in turn stimulates mitogen-activated protein kinases in the thick ascending limb of the rat kidney.
Gu
Ruimin
R
Department of Physiology, Harbin Medical University, Harbin, China.
Jin
Yan
Y
Zhai
Yuanyuan
Y
Yang
Lei
L
Zhang
Chengbiao
C
Li
Wennan
W
Wang
Lijun
L
Kong
Shumin
S
Zhang
Yunhong
Y
Yang
Baofeng
B
Wang
Wen-Hui
WH
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008954:Models, Biological; D009281:Naphthalenes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013047:Specific Pathogen-Free Organisms; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D009281:Naphthalenes; D024661:Potassium Channels, Inwardly Rectifying; C545649:Ptger3 protein, rat; D011725:Pyridines; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C058819:calphostin C; D015232:Dinoprostone; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one