Atrial natriuretic peptide stimulates Cl- transport in retinal pigment epithelial cells.
To study the regulatory role of atrial natriuretic peptide (ANP) on the Cl- transport activity of retinal pigment epithelial (RPE) cells, RPE cells from rabbits were cultured and exposed to ANP and other reagents under perfusion. The changes in intracellular Cl- concentration ([Cl-]i) were continuously recorded using a Cl(-)-sensitive fluorescent dye. The cGMP content was estimated by radioimmunoassay. ANP increased the cGMP content and the [Cl-]i in RPE cells. A guanylate cyclase activator, nitric oxide, and a cell permeable cGMP precursor, 8-Br-cGMP, also increased the level of cGMP and the [Cl-]i. A guanylate cyclase inhibitor, LY83583, an inhibitor of cGMP-dependent protein kinase, KT5823, and an inhibitor of Na+/K+/2Cl- cotransporter, bumetanide, diminished or abolished the ANP-induced increase in [Cl-]i. ANP facilitates Cl- accumulation in RPE cells, which is mediated by guanylate cyclase, cGMP-dependent protein kinase, and the Na+/K+/2Cl- cotransporter.
Mikami
Y
Y
Department of Pharmacology, Kansai Medical University, Osaka, Japan.
Hara
M
M
Yasukura
T
T
Uyama
M
M
Minato
A
A
Inagaki
C
C
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011817:Rabbits; D011863:Radioimmunoassay; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters
D000634:Aminoquinolines; D002352:Carrier Proteins; D002712:Chlorides; D005456:Fluorescent Dyes; D047428:Protein Kinase Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; C041715:6-anilino-5,8-quinolinedione; D012964:Sodium; D011494:Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D011188:Potassium