title: Actions of a novel water-soluble benzodiazepine-receptor agonist JM-1232(-) on synaptic transmission in adult rat spinal substantia gelatinosa neurons.
abstract: 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 JM-1232(-). 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(-).
authors.affiliation: Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Uemura
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Fujita
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Sakaguchi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kumamoto
mesh_terms: D000818:Animals; D058785:GABA-A Receptor Agonists / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D012995:Solubility; D013376:Substantia Gelatinosa / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014867:Water / Q000737:chemistry
chemical_list: C534223:3-(2-(4-methyl-1-piperazinyl)-2-oxoethyl)-2-phenyl-3,5,6,7-tetrahydrocyclopenta(f)isoindol-1(2H)-one; D058785:GABA-A Receptor Agonists; D054833:Isoindoles; D010879:Piperazines; D011963:Receptors, GABA-A; D014867:Water