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Latexin, the endogenous protein inhibitor of the A/B subfamily of metallocarboxypeptidases, is expressed in small nociceptive neurons in sensory ganglia and in a subset of neurons in the telencephalon. In this study, we generated latexin-deficient mice that exhibited increased tail-flick latency compared to wild-type animals upon noxious heat stimulation. The reduced pain sensitivity in the mutants was rescued by the systemic administration of a plant carboxypeptidase inhibitor that inhibits the A/B subfamily of metallocarboxypeptidases. These findings suggest that latexin is involved in the transmission of pain.

The increase in intracellular Ca2+ concentration, [Ca2+]i, induced by isomers of 2-(carboxycyclopropyl)glycine (CCG) was examined in cultured rat hippocampal neurons. Some CCG isomers and N-methyl-D-aspartate (NMDA) increased [Ca2+]i in a concentration dependent manner. The 2S,3R,4S isomer of CCG (L-CCG-IV) was the most potent in elevating [Ca2+]i, and its activity was more than 100 times higher than that of NMDA and about 10 times higher than that of L-glutamate. The increase in [Ca2+]i was effectively blocked by NMDA blockers and Mg2+, and was markedly augmented by the addition of a low concentration of glycine. L-CCG-IV would be a useful tool for elucidation of functions of NMDA receptors.

The effect of ibotenic acid on the crayfish neuromuscular junction was investigated. Ibotenate reduced dose-dependently the amplitude of the excitatory junctional potentials (EJPs) elicited by repetitive stimulation of the excitatory axons. Ibotenate did not affect facilitation of successive EJPs. The decrease in the EJP amplitude caused by ibotenate was almost completely blocked by picrotoxin. A quantum analysis of extracellularly recorded EJPs demonstrated that the mean quantum content was reduced by ibotenate without remarkable change in unit size. Ibotenate increased the conductance change induced by ibotenate was observed even if the glutamate receptor was completely desensitized by the prolonged application of glutamate. From an analysis of the dose-response curve of GABA with or without ibotenate, it is suggested that ibotenate acts on the GABA receptor in the crayfish neuromuscular junction.

Anisatin depressed the conductance increase produced by GABA in a non-competitive manner and decreased the amplitude of the inhibitory junctional potentials. The presynaptic inhibition was depressed by anisatin in the similar concentrations to those of picrotoxin. The blockade of the presynaptic inhibition by anisatin was irreversible, whereas the effect of anisatin on postsynaptic inhibition subsided after prolonged washing of the preparation.