Cyclic GMP formation induced by muscarinic receptors is mediated by nitric oxide synthesis in rat cortical primary cultures.

In rat primary cortical cultures, carbachol caused a time- and concentration-dependent increase in guanosine cyclic 3',5'-monophosphate (cGMP) levels, which was antagonized by the muscarinic antagonist atropine. Glutamate and sodium nitroprusside also caused large increases in cGMP levels, as previously reported. Two nitric oxide (NO) synthase inhibitors, L-NG-nitroarginine and L-NG-monomethylarginine, were tested for their ability to inhibit the carbachol- and the glutamate-induced cGMP formation. The cGMP response to carbachol was decreased by both compounds in a dose-dependent fashion. The effect of L-NG-nitroarginine was competitively reversed by addition of an excess of L-arginine. Similarly, the stimulatory effect of glutamate on cGMP levels was antagonized by L-NG-nitroarginine and L-NG-monomethylarginine. Hemoglobin, a scavenger of NO, also blocked the carbachol-stimulated cGMP production. These results indicate that muscarinic receptor-stimulated cGMP formation in rat cerebral cortex is mediated by NO.