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

Control of serotonin release and synthesis by amino acid neurotransmit ters 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 newl y formed [H-3]serotonin [H-3]5-HT from [H-3]-tryptophan only in rostra l 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 wel l 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) recept or agonist, induced a decrease of 5-HT release in rostral raphe cells. These observations suggest that monoamine release was entirely mediat ed by GABA(A) receptors in caudal raphe cells although GABA(A) and GAB A(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-methy l-D-aspartate (10(-4) M) enhanced 5-HT metabolism and the induced-effe ct was antagonized by the selective N-methyl-D-aspartate receptor anta gonist D,L-2 amino-5-phosphonovaleric acid. Quisqualate (10(-5) M) sti mulated [H-3]5-HT release only in caudal raphe cells. This effect was mimicked by S)-a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, a quisqualate ''ionotropic'' receptor agonist, this increase being bloc ked by 6,7-dinitroquinoxaline 2.3-dione. These observations suggest th at the glutamate stimulating-induced effect on serotonin metabolism is entirely mediated by N-methyl-D-aspartate receptor-type in rostral ra phe cells and that quisqualate ''ionotropic'' receptors are also invol ved 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 dif ference in amino acid receptor-types involved in the control of seroto nin metabolism are observed according to the rostral or caudal origin of raphe cells.