[SECOND MESSENGERS IN PRESYNAPTIC REGULATION OF GLYCINERGIC SYNAPSE ON THE FROG MOTONEURON].

Abstract

The possible pathways of inhibitory influences mediated by two kinds of metabotropic receptors, group III metabotropic glutamate receptors (mGluRs III) and GABAB receptors (GABABRs) to the miniature glycinergic events were investigated in the isolated spinal cord of the frog Rana ridibunda. The glycinergic events prevailed within the miniature inhibitory activity of motoneurons [3]. Selective agonists of GABABRs (baclofen) and group III mGluR (LAP4) reduce the frequency of miniature events to 48.0 ± 5.56% (n = 8) and 48.5 ± 8.6% (n = 5) respectively. The mean amplitude of miniature potentials was not modified significantly which indicates the presynaptic mode of their action on the synaptic transmission. To reveal the stages of metabotropic receptors regulatory effects on the glycine exocitosis the application of their selective agonists was performed after selective blockade of putative links of glycinergic transmission modulation. It was shown that the mGluRsIII influences are due to the negative feedback with adenylyl cyclase (AC) whereas the following step is formed by protein kinase A (PKA), because their selective blockade eliminate the effect of group III mGluRs activation. The AC is not involved in transdusing the GABABRs signal to the glycine miniature activity because SQ22536, an AC-inhibitor does not eliminate the inhibitory action of baclofen. The action of GABABRs depends on the activity of the phospholipase C (PLC) because its inhibition with U73122 prevents the effect of baclofen. The next possible link of this pathway could be the protein kinase C (PKC); but it is not involved in the realization of GABABRs influences because the PKC blocker (GF 109302X) does not modify the baclofen effect. The common link of group III mGluRs and GABABRs influences on the glycinergic miniature activity realization can be the inositol trisphosphate receptors (IP3Rs) that regulate the Ca2+ outflow from the nerve terminal depots and are connected (according to the literature data) with PKA, cAMP and PLC. In our experiments 2-APB, an IP3Rs antagonist, reduced to 26 ± 8% (n = 7) the frequency of glycinergic miniature activity and prevented the inhibitory effects of group III mGluRs and GABABRs. Our data suggest that collision and cross-talk of these Glu- and GABA-metabotropic pathways which was described earlier [2] may take place at this level.