1. Modulatory actions of serotonin (5-hydroxytryptamine, 5-HT) on excitatory postsynaptic currents (EPSCs) were studied with whole-cell recordings from superficial dorsal horn (SDH) neurones in neonatal rat spinal cord slices. In one-third of SDH neurones, 5-HT induced a sustained potentiation of evoked EPSCs lasting for more than 30 min after wash-out. This potentiation was often preceded by a transient suppression of EPSCs. 2. Serotonin differentially modulated the frequency of miniature EPSCs recorded in the presence of tetrodotoxin (TTX) according to the SDH neurones, producing a transient suppression, a transient facilitation or a long-lasting facilitation.3. The 5-HTIA-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin suppressed the amplitude of evoked EPSCs and frequency of miniature EPSCs in a reversible manner. In contrast, the 5-HT2-receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and a-methyl-5-HT induced long-lasting potentiations of EPSC amplitude and miniature EPSC frequency. 4. Neither the mean amplitude nor the kinetics of miniature EPSCs were affected by 5-HT during the sustained facilitation of miniature EPSC frequency, suggesting that the facilitatory effect of 5-HT was presynaptically mediated. The 5-HT-induced long-lasting facilitation of miniature EPSC frequency was observed also in Ca2+-free, Mg2+ solution. 5. The long-lasting facilitation of evoked EPSC amplitude and miniature EPSC frequency by 5-HT was mimicked by the phorbol ester, phorbol 12,13-dibutyrate (PDBu), and blocked reversibly by the protein kinase C (PKC) inhibitor, calphostin C. Forskolin applied together with 3-isobutyl-1-methylxanthine (IBMX) had no effect on the evoked EPSCs. 6. We conclude that serotonin can induce a long-lasting facilitation of evoked EPSCs and spontaneous release of excitatory transmitter at SDH synapses of rat spinal cord. Our results suggest that intracellular PKC linked to the 5-HT2 receptor may mediate this effect by directly activating the exocytotic machinery.5-Hydroxytryptamine (5-HT)-induced synaptic modulation has been characterized at invertebrate synapses, where 5-HT can produce a short-or long-lasting facilitation of transmitter release (Brunelli, Castellucci & Kandel, 1976; Glusman & Kravitz, 1982; Dixon & Atwood, 1989; Dale & Kandel, 1990). A long-lasting presynaptic facilitation by 5-HT has also been reported at goldfish central synapses (Mintz & Korn, 1991) and in mammalian autonomic ganglia (Nishimura & Akasu, 1989

We investigated the effects of gabapentin (GBP) on glutamatergic synaptic transmission in the dorsal horn of the rat spinal cord. Patch clamp whole cell recordings were made from superficial and deep dorsal horn neurons of rat spinal cord slices. In the majority of neurons in the superficial lamina, GBP decreased the amplitudes of evoked excitatory postsynaptic currents (evoked EPSCs) mediated by either non-NMDA or NMDA receptors. In contrast, neurons in the deep lamina showed variable effects, with a lower incidence of decrease in amplitude of evoked EPSCs and a subset of neurons showing an increase in amplitude of evoked NMDA receptor-mediated EPSCs. No enhancement of evoked non-NMDA receptor-mediated EPSCs was observed in either lamina. To determine whether the observed effects of GBP are presynaptic and/or postsynaptic, spontaneous miniature excitatory postsynaptic currents (mEPSCs) were studied. In neurons that showed a decrease in its frequency of mEPSCs by GBP, no change in the amplitude or shape accompanied the effect. On the other hand, in neurons that showed an increase in the frequency of NMDA receptor-mediated mEPSCs, the effect accompanied an increase in amplitude. These results suggest that GBP presynaptically inhibits glutamatergic synaptic transmission predominantly in the superficial lamina, while postsynaptically enhancing NMDA receptor-mediated transmission in some neurons of the deep lamina. The antinociceptive effects of GBP may involve the inhibition of the release of excitatory amino acids from presynaptic terminals.

SUMMARY1. Tight-seal whole-cell recordings were made from marginal neurones visually identified in thin slices of 1-to 2-week-old rat lumbar spinal cord. Excitatory postsynaptic currents (EPSCs), either evoked by extracellular stimulation or those arising spontaneously in tetrodotoxin, i.e. miniature EPSCs (mEPSCs), were recorded after blocking inhibitory synaptic inputs with strychnine and bicuculline.2. The EPSCs were abolished reversibly by kynurenic acid or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) but not affected by (+ )-2-amino-5-phosphonovalerate (APV), suggesting that they were mediated by non-NMDA (N-methyl-D-aspartate) glutamate receptors.

No abstract

In Japan, poisonings by the glyphosate (GLYP)-containing herbicide Roundup and the gluphosinate (GLUF)-based herbicide BASTA have been increasing since about 1987. We applied the gas chromatography-mass spectrometry (GC-MS) method of analysis, on which we have already reported in regard to the determination of the blood serum level of GLUF and its metabolite, for the determination of serum and urinary levels of GLYP and its metabolite aminomethyl phosphonic acid (AMPA). Derivatization using N-methyl-N-(tert-butyldimethylsilyl) trifluoroacetamide was completed at a temperature of 80 degrees C after 30 min, and the detection limit of GLYP was 10 pg using m/z 454 and that of AMPA was 1 pg using m/z 396. The full mass spectra of 100 pg GLYP and of 10 pg AMPA were obtained easily. In extractions for which the Isolute HAX cartridge was employed, the mean recovery rate of GLYP and AMPA added to serum to yield concentrations of 10-0.1 microg/mL (n = 5) was 91.6 +/- 10.6% (or better), whereas that of GLYP and AMPA added to urine to yield concentrations of 100-1.0 microg/mL (n = 10) was 93.3 +/- 6.6% (or better), both of which were good rates. Also, using this method of analysis, the presence of GLYP was identified in the full mass spectra obtained from the serum of a patient who may or may not have ingested Roundup.