Molecular mechanism of excitatory effect of adenosine on neurotransmission

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Adenosine, an endogenous brain substance is considered to be an inhibitory and excitatory neuromodulator in neurotansmission in the central nervous system. The mechanism of excitatory effect of adenosine has not yet been studied in detail. The purpose of the present experiment was to clarify the mechanism of excitatory effect of adenosine using the superior colliculus of the rat in which adenosine shows potent excitatory effect on neurotransmission.(1) Study using in vivo preparation of the rat.The application of adenosine in the vicinity of recording electrode enhanced the synaptic potential (150-170% of original level) evoked in the superficial gray layr of the superior colliculus after electrical stimulation to optic nerve. Systemic application of EHNA,an adenosine diaminase inhibitor, also enhanced the synaptic potential as observed in the topical application of adenosine as mentioned above. Usig microdialysis technique, glutamate release, an excitatory transmitter in this region w … More as determined during application of adenosine or EHNA.Application of EHNA and topical application of adenosine increased the release of glutamate (130%) in the dialisate.(2) Effect of adenosine on isolated cultured neuron of superior colliculus.To test the postsynaptic effect of adenosine, its effect on the isolated cultured superior colliculus neuron was investigated using whole cell patch clamp method. The K^+-conductance of the membrane was increased by application of adenosine. By applying agonists and antagonists of adenosine receptors, this effect was found to be mediated through P_<2Y> receptor.(3) Involvement of A_<2A> receptors of the excitatory effect of adenosine.The excitatory effect of adenosine or EHNA was blocked by the A_<2A> antagonist, KF17837 whereas it was not counteracted by the DPCPX,an A_1 antagonist. By the TR-PCR method, the presence of A_2 mRNA was found in the superior colliculus.These results indicate that the excitatory effect of adenosine in the superior colliculus was mediated through A_<2A> receptor which enhance presynaptically the release of glutamate, whereas there is a possibility that adenosine may inhibit the postsynaptic activity by increasing the K^+-conductance, and this can be apparently masked by presynaptic excitatory action of adenosine. Less