GLUTAMATE, GABA, GLYCINE AND TAURINE MODULATE SEROTONIN SYNTHESIS AND RELEASE IN ROSTRAL AND CAUDAL RHOMBENCEPHALIC RAPHE CELLS IN PRIMARY CULTURES

Control of serotonin release and synthesis by amino acid neurotransmitters was investigated in rat rostral and caudal rhombencephalic raphe cells in primary cultures respectively. Endogenous amounts of taurine, glycine, GABA and glutamate were measured in both types of cultures. These amino acids were spontaneously released to the incubating medium. Exogenous taurine (10(-4) M) inhibited release and synthesis of newly formed [H-3]serotonin [H-3]5-HT from [H-3]-tryptophan only in rostral raphe cells. Glycine (10(-3) M) decreased [H-3]5-HT release in both types of cells. synthesis being diminished only in rostral raphe cells. Glycine inhibitory effect was totally blocked by strychnine (5 x 10(-5) M). GABA (10(-4) M) reduced [H-3]5-HT metabolism in rostral as well as caudal raphe cells. This effect was totally antagonized in caudal and partially in rostral raphe cells by bicuculline (5 x 10(-5) M) a GABA(A) receptor antagonist. Baclofen (5 x 10(-5) M), a GABA(B) receptor agonist, induced a decrease of 5-HT release in rostral raphe cells. These observations suggest that monoamine release was entirely mediated by GABA(A) receptors in caudal raphe cells although GABA(A) and GABA(B) receptors were involved in control of 5-HT metabolism in rostral raphe Cells. L-glutamate (10(-4) M) stimulated 5-HT metabolism in both types of cells, effect totally blocked by PK26124 (10(-6) M). N-methyl-D-aspartate (10(-4) M) enhanced 5-HT metabolism and the induced-effect was antagonized by the selective N-methyl-D-aspartate receptor antagonist D,L-2 amino-5-phosphonovaleric acid. Quisqualate (10(-5) M) stimulated [H-3]5-HT release only in caudal raphe cells. This effect was mimicked by (RS)-a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, a quisqualate ''ionotropic'' receptor agonist, this increase being blocked by 6,7-dinitroquinoxaline 2.3-dione. These observations suggest that the glutamate stimulating-induced effect on serotonin metabolism is entirely mediated by N-methyl-D-aspartate receptor-type in rostral raphe cells and that quisqualate ''ionotropic'' receptors are also involved in caudal raphe cells. Taken together these results show that [H-3]5-HT metabolism is controlled by taurine, glycine, GABA and glutamate in rhombencephalic raphe cells in primary cultures. However, some difference in amino acid receptor-types involved in the control of serotonin metabolism are observed according to the rostral or caudal origin of raphe cells.