Molecular mechanism of excitatory effect of adenosine on neurotransmission

腺苷是一种内源性脑内物质，在中枢神经系统的神经传递中被认为是一种抑制性和兴奋性的神经调质。腺苷兴奋作用的机制尚未详细研究。本实验的目的是利用腺苷对神经传递具有强兴奋作用的大鼠上级丘来阐明腺苷兴奋作用的机制。(1)用大鼠在体标本进行研究。在记录电极附近应用腺苷，可使电刺激视神经后在上级丘浅灰质层诱发的突触电位增强150-170%。全身应用腺苷二氨酶抑制剂EHNA也增强了突触电位，如在上述腺苷局部应用中所观察到的。利用微透析技术，在此区域的兴奋性递质谷氨酸的释放， ...更多信息 应用EHNA和局部应用腺苷增加了二磺酸盐中谷氨酸的释放（130%）。(2)腺苷对离体培养上级丘神经元的作用：采用全细胞膜片钳技术观察腺苷对离体培养上级丘神经元的突触后作用。膜的K ^+电导率通过腺苷的应用而增加。通过应用腺苷受体激动剂和拮抗剂，发现这种作用是通过P受体介导的。<2Y>(3)腺苷兴奋作用的A受体参与腺苷或EHNA的兴奋作用可被A受体拮抗剂KF 17837阻断，而不能被A_1受体拮抗剂DPCPX拮抗。<2A><2A>用TR-PCR方法在上级丘中检测到A_2mRNA的存在，提示腺苷对上级丘的兴奋作用是通过A_受体介导的，它能促进突触前谷氨酸的释放，而腺苷可能通过增加K ^+传导抑制突触后活动。<2A>并且这可以明显地被腺苷的突触前兴奋作用掩盖。少

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