Inhibitory effects of motilin, somatostatin, [Leu]enkephalin, [Met]enkephalin, and taurine on neurons of the lateral vestibular nucleus: Interactions with γ-aminobutyric acid

Motilin, [Met]enkephalin, [Leu]enkephalin, somatostatin, taurine, γ-aminobutyric acid (GABA), and glycine were tested for their effects on Deiters neurons of the lateral vestibular nucleus in rabbits. Iontophoresis was carried out with multibarrelled micropipettes. All four peptides and three amino acids produced depression of neuron firing. No facilitatory responses were observed. The depressant action of each peptide when iontophoresed alone was dose-dependent and was rapid in onset and recovery. Their characteristic actions suggest the possibility of their independent roles as strong inhibitors, although the experimental paradigm does not allow conclusions about the individual potency of each peptide. When GABA was administered together with motilin, [Met]enkephalin, or somatostatin, the effects of the peptide and GABA were additive, producing depression greater than that with application of either substance alone. When GABA was applied in conjunction with [Leu]enkephalin, more complex interactions were observed. At low iontophoretic currents, [Leu]enkephalin antagonized the action of GABA, producing a depression less than that of GABA alone and of considerably slower onset, suggesting an additional modulatory effect. These observations support the conclusion that all substances tested are chemical mediators in the lateral vestibular nucleus and [Leu]enkephalin may be a neuromodulator as well. Because recent immunocytochemical studies indicate that Purkinje cells in the cerebellar cortex are chemically heterogeneous and exhibit immunoreactivity for motilin, taurine, the enkephalins, and somatostatin, as well as for the GABA-synthesizing enzyme glutamic acid decarboxylase, it is suggested that the Purkinje cell projections to vestibular and cerebellar nuclei are multimodal in their chemical coding. The uniformly depressant action of the peptides and amino acids reported here is consistent with earlier observations that Purkinje cells exert an inhibitory influence on the vestibular and central cerebellar nuclei.