ガラニンはラット脊髄膠様質ニューロンの興奮性シナプス伝達を修飾する

抄録

Galanin, a 29/30 amino acid neuropeptide, is thought to play a pivotal role in various physiological functions including nociception. Galanin and its receptors exist in spinal dorsal root ganglion and spinal dorsal horn neurons. Although intrathecal administration of galanin results in a biphasic modulation of nociceptive behavior such that galanin at low and high doses produces nociception and antinociception, respectively, cellular mechanisms for this result have not been elucidated yet. By use of the whole-cell patch-clamp technique, we investigated the effects of galanin on excitatory synaptic transmission in substantia gelatinosa (SG) neurons of rat spinal cord slices. Superfusing galanin for 2 min dose-dependently produced an outward current at -70 mV in a range of 0.03-1 μM (EC₅₀: 0.078 μM) in about 50% of SG neurons tested. This effect was mimicked by M617, a selective galanin receptor 1 (GalR1) agonist. Galanin also dose-dependently enhanced the frequency of sEPSC without a change in the amplitude at low doses at which galanin produced a minimal outward current; this effect was maximal at about 0.03 μM and resistant to tetrodotoxin. These results indicate that galanin at lower doses enhances the spontaneous release of L-glutamate from nerve terminals while in addition to this presynaptic effect, galanin at higher doses produces a membrane hyperpolarization, possibly by activating GalR1s in the SG; these actions could contribute to at least a part of the behavioral effects of galanin. [J Physiol Sci. 2008;58 Suppl:S134]