Inhibition by lithium of cyclic GMP formation without inhibition of nitric oxide generation in the mouse neuroblastoma cell (N1E-115).
We investigated the effects of lithium ion (Li+) on muscarinic receptor-mediated nitric oxide (NO) generation, and guanylate cyclase (GCase) activation using the mouse neuroblastoma clone, N1E-115. The levels of released NO were determined by measuring the levels of nitrite/nitrate in the incubation medium, and the activity of GCase was measured with an assay for cellular cyclic [3H] GMP levels. We determined that Li+ had no effects on muscarinic receptor-activated elevation of nitrite/nitrate levels, which were significantly inhibited by 100 microM L-NG-monomethylarginine, although it has been reported that Li+ inhibits muscarinic receptor-activated cyclic GMP formation in the cells. In addition, Li+ inhibited the cyclic GMP formation induced by an NO donor, sodium nitroprusside (SNP), in both intact cells and a crude cellular homogenate; thus, the inhibition by Li+ of muscarinic receptor-mediated cyclic GMP synthesis appeared to be at the level of GCase, but not NO synthase.
Department of Neuro-psychiatry, Keio University School of Medicine, Tokyo, Japan.
F
F
Shintani
S
S
Kanba
T
T
Nakaki
R
R
Nakamura
K
K
Sato
G
G
Yagi
E
E
Richelson
R
R
Kato
M
M
Asai
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008094:Lithium / Q000494:pharmacology*; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009599:Nitroprusside / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019323:omega-N-Methylarginine
D018727:Muscarinic Antagonists; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D002217:Carbachol; D001120:Arginine; D008094:Lithium; D006162:Guanylate Cyclase; D006152:Cyclic GMP