Inhibitory effects of nicorandil on rat mesangial cell proliferation via the protein kinase G pathway.
We investigated the effects of nicorandil, which is a hybrid between a nitrate and an ATP-sensitive potassium channel (K(ATP)) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 microM to 1 mM inhibited [(3)H]thymidine incorporation into rat mesangial cells in a concentration-dependent manner. Nicorandil (1 microM to 1 mM) also inhibited the number of cells. Nicorandil increased cyclic guanosine 3',5'-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell proliferation. We also examined the effects of K(ATP) mediators. Cromakalim, a K(ATP) activator, and glibenclamide, a K(ATP) inhibitor, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell proliferation are mediated via the protein kinase G pathway.
Segawa
K
K
Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka 807-8555, Japan. k-segawa@med.uoeh-u.ac.jp
Minami
K
K
Shiga
Y
Y
Shiraishi
M
M
Sata
T
T
Nakashima
Y
Y
Shigematsu
A
A
D000470:Alkaloids / Q000378:metabolism; D000818:Animals; D002227:Carbazoles; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D007211:Indoles; D008297:Male; D008751:Methylene Blue / Q000378:metabolism / Q000494:pharmacology; D020108:Nicorandil / Q000378:metabolism / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013936:Thymidine / Q000378:metabolism
D000470:Alkaloids; D002227:Carbazoles; D007211:Indoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C073601:KT 5823; D020108:Nicorandil; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008751:Methylene Blue; D013936:Thymidine