title: Time-Dependent Effect of Melatonin on Glutamic Acid Decarboxylase Activity and CI Influx in Rat Hypothalamus.
abstract: Abstract The objective of the first series of experiments was to assess whether melatonin treatment modifies the activity of the y-aminobutyric acid synthesizing enzyme, glutamic acid decarboxylase, in the preoptic-medial basal hypotnalamic area, cerebral cortex and cerebellar cortex of rats receiving 25 to 300 mug of melatonin in the early morning and late evening in the diurnal cycle. A significant increase of apparent V(max) and K(m) of the enzyme was found in the hypothalamus of rats killed at the 12th h of the light phase (i.e. the time when lights were turned off) and receiving 25 to 300 mug/kg of melatonin 3 h earlier. In the early morning, only a 300 mug/kg dose of melatonin (injected in the 1st h of the light phase) was effective to increase V(max) and K(m) of hypothalamic glutamic acid decarboxylase 3 h later. In cerebral and cerebellar cortices, increases in V(max) and K(m) of enzyme activity were apparent only in the evening and with the highest melatonin dose employed (300 mug/kg). In a second series of experiments the activity of melatonin to modify in vitro(36)CI influx by 900 x g pellets of rat preoptic-medial basal hypothalamic area was studied at the 4th and 12th h of the light phase of daily photoperiod. Melatonin increased (36)CI(-) influx at a minimum concentration of 100 nM (in the morning) or 10 nM (in the evening). The effect of melatonin on (36)CI(-) influx was prevented by co-incubation with 100 muM picrotoxin. Addition of 10 to 100 muM of y-aminobutyric acid to the resuspended 900 x g pellets brought about a dose-dependent increase of (36)CI (-) influx. Preincubation with melatonin at threshold doses of 1 muM (in the morning) or 0.1 muM (in the evening) significantly augmented y-aminobutyric acid effect on (36)CI(-) uptake. These results indicate that melatonin facilitates pre- and postsynaptic activities of y-aminobutyric acid neurons, particularly in the hypothalamus, through an effect that displays a diurnal sensitivity compatible with the documented activity of the hormone on a number of physiological functions.
authors.affiliation: Departamento de Fisiologia, Facultad de Medicina, Universidad de Buenos Aires, CC 243, 1425 Buenos Aires, Argentina.
authors.forename: R E
authors.initials: RE
authors.lastname: Rosenstein
authors.forename: A G
authors.initials: AG
authors.lastname: Estévez
authors.forename: D P
authors.initials: DP
authors.lastname: Cardinali