Pharmacological characterization of postsynaptic receptors for excitatory amino acids in Purkinje cell dendrites in the guinea pig cerebellum.

Abstract

The responses of Purkinje cell dendrites to iontophoretically applied L-glutamate, L-aspartate, kainate and quisqualate were intradendritically recorded in the in vitro slice preparation of the guinea pig cerebellum. Kainate and quisqualate were found to be very potent excitants, while N-methyl-DL-aspartic acid (NMDLA) caused little or no effect on Purkinje cell dendrites. Thus, kainate and quisqualate receptors were certainly present, while there appeared to be no NMDA-preferring receptor in Purkinje cell dendrites in the guinea pig cerebellum. The effects of several antagonists such as 2-amino-5-phosphonovaleric acid (APV), gamma-D-glutamylglycine (gamma-DGG), NMDLA and glutamic acid diethylester (GDEE) etc. on responses to L-glutamate and L-aspartate were compared in order to search for potent and selective antagonists capable of differentiating the response to L-glutamate from that to L-aspartate. Among these compounds tested, APV and gamma-DGG were found to be potent and selective antagonists to the L-aspartate-induced depolarization without affecting responses to L-glutamate. These two agents may be useful, at least in the in vitro study, to the identification of the excitatory amino acid which function as a neurotransmitter at the synapses formed by the climbing fiber or parallel fiber with Purkinje cell dendrites.