CARNOSINE AND BETA-ALANINE RELEASE IS STIMULATED BY GLUTAMATERGIC RECEPTORS IN CULTURED RAT OLIGODENDROCYTES

Oligodendrocytes obtained from rat brain 0-2 A progenitor cells and di fferentiated in culture take up beta-alanine and synthesize carnosine (beta-Ala-His). The present study was designed to determine whether ca rnosine and beta-alanine are released from such cultures in response t o some stimuli. An evoked release of these substances was not observed when the cells were incubated with 1mM glutamate or 0.3 mM kainate. A ddition of 0.1 mM cyclothiazide (CTZ) to the corresponding stimulus wa s accompanied by a distinct peak of release consisting of both carnosi ne and beta-alanine. The efflux was blocked completely in the case of kainate and to 80% in the case of glutamate when 50 mu M 6,7- dinitroq uinoxaline-2,3 (1H,4H)-dion (DNQX) was added to the cells at the same time as the receptor agonist. An increase of the efflux was observed i n the presence of Zn2+. This effect was concentration- dependent. Tota l substitution of NaCl in the efflux medium by LiCl caused only a part ial reduction of the release. GABA or 55 mM KCl showed only negligible effect. A large release of carnosine and beta-alanine was observed wh en oligodendrocyte cultures were treated with Ca2+ ionophore A 23187. These results suggest that oligodendrocytes exhibit a glutamate recept or-mediated release of carnosine and beta-alanine. The release is depe ndent on elevated intracellular Ca2+ concentration. (C) 1998 Wiley-Lis s, Inc.