The role of nitric oxide in motoneuron spike activity and muscarinic-evoked changes in cGMP in the CNS of larval Manduca sexta

Nitric oxide and muscarinic agonists both stimulate motoneuron spike activi ty and cGMP production in the central nervous system of larval Manduca sext a. The possible role of nitric oxide in mediating muscarinic changes in exc itability was examined by measuring cGMP accumulation and proleg motoneuron activity while blocking or mimicking the production of nitric oxide. All t he muscarinic-induced changes in cGMP are blocked by the nitric oxide-synth ase inhibitor, nitro-l-arginine, an effect that is partially prevented by c o-incubation with arginine, Action potential blockage with tetrodotoxin rev ealed that muscarinic increases in cGMP production have both spike-dependen t and spike-independent mechanisms. Furthermore, nitric oxide donors can in crease proleg motoneuron activity and this stimulation is blocked by 1H-{1, 2,4}oxadiazolo{4,3-a}quinoxalin-1-one suggesting that it is mediated by a n itric oxide-sensitive guanylyl cyclase. In contrast, nitro-1-arginine and a variety of other nitric oxide-synthase inhibitors and nitric oxide scaveng ers have no significant effect on muscarinic stimulation of motoneuron acti vity. Therefore, although a nitric oxide sensitive guanylyl cyclase is capa ble of elevating spike activity and muscarinic agonists can increase cGMP, this mechanism is not necessary for the normal muscarinic increase in excit ability. It is concluded that muscarinic receptors are coupled to nitric ox ide and cGMP production in neurons other than those controlling the prolegs .