PHARMACOLOGICAL CHARACTERISTICS OF AN OUTWARD CURRENT PRODUCED BY BETA-HYDROXY-L-GLUTAMIC ACID ON A SNAIL NEURON

An outward current (I-out) was produced by stereoisomers of beta-hydro xy-L-glutamic acid (L-BHGA), an L-glutamic acid (L-Glu) derivative, ap plied by brief pneumatic pressure ejection on an identifiable neurone type, v-LCDN (ventral-left cerebral distinct neurone), of Achatina ful ica Ferussac. However, L- and D-Glu were almost ineffective on this ne urone type. The pharmacological features of this I-out caused by L-BHG A were elucidated in the present study. According to the dose (pressur e duration) response studies on the L-BHGA stereoisomers that produced the I-out, the effective potency of threo-L-BHGA was approximately si milar to that of erythro L-BHGA. The dose (pressure duration)response curve of quisqualic acid was shifted towards the left direction from t hose of threo- and erythro-L-BHGA, suggesting that the binding activit y 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 (I-in) on this neurone type, in contrast to the I-ou t caused by L-BHGA. beta-Alanine and taurine had absolutely no effect. Therefore, no amino acid inhibitory neurotransmitter candidate was fo und for this neurone type except for L-BHGA,It was assumed that L-BHGA , in either threo- or erythro-configuration, would be an inhibitory ne urotransmitter for this neurone type. Mammalian L-Glu receptor antagon ists. D(-)-AP-5, (+/-)-CPP, CNQX and L(+)-AP-3, applied by perfusion, showed no effect on the I-out of V-LCDN caused by threo L-BHGA, indica ting that the features of the inhibitory receptor activated by L-BHGA were much different from those of any type of the mammalian L-Glu rece ptors. Among the inhibitors of ATP sensitive K+ channel, glipizide sig nificantly inhibited the I-out caused by threo-L-BHGA, whereas tolbuta mide did not. Inhibitors of intracellular signal transduction systems, H-7, H-8, H-9, staurosporine, calphostin C, KT5823 and W-7, had no ef fect on the I-out caused by threo-L-BHGA, suggesting that the receptor s activated by threo L-BHGA would be ionotropic.