Carnosine and beta-alanine release is stimulated by glutamatergic receptors in cultured rat oligodendrocytes

Abstract

Oligodendrocytes obtained from rat brain 0-2 A progenitor cells and differentiated in culture take up beta-alanine and synthesize carnosine (beta-Ala-His). The present study was designed to determine whether carnosine and beta-alanine are released from such cultures in response to some stimuli. An evoked release of these substances was not observed when the cells were incubated with 1 mM glutamate or 0.3 mM kainate. Addition of 0.1 mM cyclothiazide (CTZ) to the corresponding stimulus was accompanied by a distinct peak of release consisting of both carnosine and beta-alanine. The efflux was blocked completely in the case of kainate and to 80% in the case of glutamate when 50 microM 6,7-dinitroquinoxaline-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 in the presence of Zn2+. This effect was concentration-dependent. Total substitution of NaCl in the efflux medium by LiCl caused only a partial reduction of the release. GABA or 55 mM KCl showed only negligible effect. A large release of carnosine and beta-alanine was observed when oligodendrocyte cultures were treated with Ca2+ ionophore A 23187. These results suggest that oligodendrocytes exhibit a glutamate receptor-mediated release of carnosine and beta-alanine. The release is dependent on elevated intracellular Ca2+ concentration.