脊髄内痛覚伝達におけるATP とアデノシンの相互作用

概要

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The last decade has seen the development of a particular interest in the role of purines in nociception. The ability of adenosine 5-triphosphate (ATP) and adenosine to alter nociceptive transmission at peripheral and central sites has been recognized. The recent discovery of P2X receptors (ion channels gated by ATP) has led to the exploration of the sources of ATP involved in initiating different types of nociception. In addition, adenosine receptors in the spinal cord have generated great interest in the development of its agonists as potential analgesic drugs. Although each role of P2X and adenosine receptors in nociceptive transmission has been examined in detail, the interaction of their receptors has never been studied. In this study, we demonstrated that extracellular ATP induces a biphasic effect such as facilitation followed by inhibition of glutamatergic excitatory synaptic transmission in dorsal horn neurons of spinal cord slice preparations by use of patch-clamp recordings. The application of ATP made an initial facilitation of glutamate release via presynaptic P2X receptors, which lasted for only a short period. ATP was rapidly metabolized to adenosine which produced an inhibition of glutamate release onto dorsal horn neurons by activating adenosine receptors for a relatively longer period. Our results indicate that extracellular ATP exerts multiple influences on nociceptive transmission in the spinal cord.
日本疼痛学会の論文