Pharmacological characteristics of an outward current produced by beta-hydroxy-L-glutamic acid on a snail neurone.

An outward current (Iout) was produced by stereoisomers of beta-hydroxy-L-glutamic acid (L-BHGA), an L-glutamic acid (L-Glu) derivative, applied by brief pneumatic pressure ejection on an identifiable neurone type, v-LCDN (ventral-left cerebral distinct neurone), of Achatina fulica Férussac. However, L- and D-Glu were almost ineffective on this neurone type. The pharmacological features of this Iout caused by L-BHGA were elucidated in the present study. According to the dose (pressure duration)-response studies on the L-BHGA stereoisomers that produced the Iout, the effective potency of threo-L-BHGA was approximately similar to that of erythro-L-BHGA. The dose (pressure duration)-response curve of quisqualic acid was shifted towards the left direction from those of threo-and erythro-L-BHGA, suggesting that the binding activity of quisqualic acid to the receptors would be stronger than those of the L-BHGA stereoisomers. GABA, glycine and L-homocysteic acid showed an inward current (Iin) on this neurone type, in contrast to the Iout caused by L-BHGA. beta-Alanine and taurine had absolutely no effect. Therefore, no amino acid inhibitory neurotransmitter candidate was found for this neurone type except for L-BHGA. It was assumed that L-BHGA, in either threo-or erythro-configuration, would be an inhibitory neurotransmitter for this neurone type. Mammalian L-Glu receptor antagonists. D(-)-AP-5, (+/-)-CPP, CNQX and L(+)-AP-3, applied by perfusion, showed no effect on the Iout of v-LCDN caused by threo-L-BHGA, indicating that the features of the inhibitory receptor activated by L-BHGA were much different from those of any type of the mammalian L-Glu receptors. Among the inhibitors of ATP-sensitive K+ channel, glipizide significantly inhibited the Iout caused by threo-L-BHGA, whereas tolbutamide did not. Inhibitors of intracellular signal transduction systems, H-7, H-8, H-9, staurosporine, calphostin C, KT5823 and W-7, had no effect on the Iout caused by threo-L-BHGA, suggesting that the receptors activated by threo-L-BHGA would be ionotropic.