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, NIE-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 11M 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.
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