Actions of a novel water-soluble benzodiazepine-receptor agonist JM-1232(-) on synaptic transmission in adult rat spinal substantia gelatinosa neurons

作者：Uemura Satoko; Fujita Tsugumi; Sakaguchi Yoshiro; Kumamoto Eiichi^*

来源：Biochemical and Biophysical Research Communications, 2012, 418(4): 695-700.

DOI：10.1016/j.bbrc.2012.01.080

• JM-1232(-)
• Antinociception
• Spinal dorsal horn
• GABA
• Glycine

Although the intrathecal administration of JM-1232(-) reportedly produces antinociception, this action has not yet been examined at the cellular level. We examined the action of JM-1232(-) on synaptic transmission in spinal substantia gelatinosa (SG) neurons which play an important role in regulating nociceptive transmission from the periphery. The whole-cell patch-clamp technique was applied to the SG neurons of adult rat spinal cord slices. Bath-applied JM-1232(-) prolonged the decay phase of GABA(A)-receptor mediated spontaneous inhibitory postsynaptic current (sIPSC) and increased its frequency without a change in amplitude. The former but not latter action was sensitive to a benzodiazepine-receptor antagonist flumazenil. JM-1232(-) also increased glycinergic sIPSC frequency with no change in amplitude and decay phase. On the other hand, glutamatergic spontaneous excitatory transmission was unaffected by JM1232(-). These results indicate that JM-1232() enhances inhibitory transmission by (1) prolonging the decay phase of GABAergic sIPSC through benzodiazepine-receptor activation and by (2) increasing the spontaneous release of GABA and glycine from nerve terminals without its activation. This enhancement could contribute to at least a part of the antinociceptive effect of intrathecally-administered JM-1232(-).

• 出版日期2012-2-24