Novel mode of nitric oxide neurotransmission mediated via S-nitroso-cysteinyl-glycine

S-nitroso-cysteinyl-glycine, a novel nitric oxide-adduct thiol compound, ca n be detected in the brain (2.3 +/- 0.6 pmol/mg protein), and released foll owing stimulation of sensory afferents to the rat ventrobasal thalamus in v ivo (resting conditions 17 nm; stimulation: 186 nm). Iontophoretic applicat ion of CysNOGly (20-80 nA) onto thalamic neurons in vivo resulted in enhanc ements of excitatory responses to either NMDA or AMPA (182 +/- 13.6% and 24 4 +/- 27.8% of control values, n = 15). CysNOGly enhanced responses to stim ulation of vibrissal afferents to 132 +/- 2.2% (n = 7) of control values. I n contrast, the dipeptide CysGly reduced responses of ventrobasal neurons t o NMDA and AMPA (54 +/- 8.4% and 55 +/- 10.8% of control, n = 5). CysNOGly was also a potent activator of soluble guanylate cyclase in vitro. Moreover , we found that NMDA elevated CysNOGly levels in vitro and this stimulatory effect was reduced by inhibitors of the neuronal NO synthase and of the ga mma -glutamyl transpeptidase, suggesting that production of NO and CysGly i s a prelude to CysNOGly synthesis. These findings suggest that the nitrosot hiol CysNOGly plays a role in synaptic transmission in the ventrobasal thal amus. We propose a novel synaptic buffering mechanism where S-nitroso-cyste inyl-glycine serves to restrict the locus of action of nitric oxide and so increase its local availability for target delivery. This could lead to a c hange in neuronal responses favouring sensory transmission similar to that seen in wakefulness or arousal in order to locally enhance transmission of persistent sensory stimuli.