Effect of melatonin on the retinal glutamate/glutamine cycle in the golden hamster retina

DANIEL A. SÁENZ; ANDREA P. GOLDIN; LUCIANA MINCES; MÓNICA CHIANELLI; MARÍA I. KELLER SARMIENTO; RUTH E. ROSENSTEIN

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Año: 2004 vol. 18 p. 1912 - 1923

0892-6638

Glutamate is the main excitatory neurotransmitter in the retina, but it is neurotoxic when present in excessive amounts. The metabolic dependence of glutamatergic neurons upon glia via the glutamate/glutamine cycle to provide the precursor for neurotransmitter glutamate is well established. Since melatonin has been shown to be neuroprotective in several systems, in the present report, its effect on the glutamate/glutamine cycle activity was examined in the golden hamster retina. Melatonin (0.1−10 nM) significantly increased retinal glutamine synthetase activity but it did not affect L-glutamine release. A characterization of the hamster retinal Lglutamine uptake mechanism was performed. This mechanism was partly Na+-dependent, and it was significantly inhibited by 2-aminobicyclo (2, 2, 1) heptane 2-carboxylic acid (BCH, a selective antagonists for the L-type system) and by α-(methylamino)-isobutyric acid (MeAIB, substrate characteristic for the A -type transporter) suggesting the coexistence of these transport systems in the hamster retina. Melatonin (0.1−10 nM) significantly increased total glutamine uptake as well as the BCH and the MeAIB-insensitive transporters activity. On the other hand, melatonin significantly decreased retinal glutaminase activity. On the basis of these results, it might be presumed that hamster retinal glutamate/glutamine cycle activity is regulated by physiological concentrations of melatonin. Furthermore, these findings suggest that a treatment with melatonin could be considered as a new approach to handling glutamate-mediated neuronal degeneration.