Circadian activity of the GABAergic system in the golden hamster retina.

Daily changes in gamma-aminobutyric acid (GABA) turnover rate were studied in the golden hamster retina. This parameter showed significant variations throughout the light-dark cycle, with minimal values during the day. Retinal glutamic acid decarboxylase (GAD) activity was higher at midnight than at noon. Moreover, [3H]GABA binding significantly varied throughout the 24-h cycle, with maximal values during the day. Saturation studies performed at 12:00 and 24:00 h indicated that the maximal concentration of [3H]GABA binding sites (Bmax) was significantly higher at noon, whereas the dissociation constant (Kd) remained unchanged. High K+-induced GABA release was significantly higher at midnight than at midday. Daily variations in retinal GABA turnover rate, GABA release, and in its specific binding persisted in golden hamsters exposed to constant darkness. In summary, these results support the idea of a circadian clock-controlled GABAergic activity in the hamster retina.

Effect of brimonidine on rabbit trabecular meshwork hyaluronidase activity.

PURPOSE: To study the presence of hyaluronidase activity in the rabbit trabecular meshwork and its regulation by brimonidine. METHODS: A spectrophotometric assay that consists of the assessment of N-acetylhexosamine groups released from hyaluronic acid was used to examine hyaluronidase activity. Cyclic adenosine monophosphate (cAMP) levels were assessed by radioimmunoassay. RESULTS: Hyaluronidase activity was detected in the rabbit trabecular meshwork. Its optimal activity was in the acid range of pH 3.8. Brimonidine significantly increased trabecular hyaluronidase-specific activity and decreased cAMP accumulation. Yohimbine significantly inhibited the effect of brimonidine on both hyaluronidase activity and cAMP accumulation. CONCLUSIONS: The finding of endogenous hyaluronidase activity in rabbit trabecular meshwork supports the hypothesis that this tissue can metabolize its own glycosaminoglycan (GAG) products. The present results suggest, however, that the hypotensive effect of brimonidine could be mediated, at least in part, by its ability to increase GAG catabolism, probably through a cAMP-independent mechanism.

Dopamine decreases melatonin content in golden hamster retina.

Dopamine significantly decreased melatonin levels in Golden hamster retinas excised at noon and incubated under light. The effect of dopamine was reversed by spiperone and clozapine (selective antagonists for D(2) and for D(4)/D(2) dopaminergic receptors, respectively) but not by SCH 23390 (a selective D(1) dopamine receptor antagonist). Both clozapine and spiperone per se significantly increased melatonin levels, whereas SCH 23390 was ineffective. Quinpirole (an agonist for D(2)-subfamily dopaminergic receptor) decreased melatonin content in retinas excised at midday. Dopamine increased, whereas quinpirole decreased, cAMP accumulation in retinas excised at noon. Retinal dopaminergic turnover rate (assessed as the ratio of 3,4-dihydroxyphenylacetic acid to dopamine) was significantly higher at midday than at midnight. In retinas excised at midnight, melatonin content in vitro was unaffected by dopamine or quinpirole. At midnight, dopamine increased cAMP accumulation, whereas quinpirole was ineffective. When hamsters were kept under constant darkness for 48 h and sacrificed at subjective midday or midnight, dopamine increased cAMP accumulation at both times, whereas quinpirole decreased this parameter only at subjective midday. Dopaminergic turnover rate was significantly higher at subjective midday than at subjective midnight. These results show that dopamine regulates melatonin biosynthesis in the Golden hamster retina.

Effect of GABA on melatonin content in golden hamster retina.

The effect of GABA on melatonin content in vitro was studied in the golden hamster retina. GABA significantly increased melatonin levels in a dose-dependent manner, its effect being reversed by a GABA(A) receptor antagonist, bicuculline, but not by saclofen, a GABA(B) antagonist. Moreover, an equimolar concentration of muscimol, a GABA(A) receptor agonist, significantly increased retinal melatonin content, whereas baclofen, a GABA(B) receptor agonist, was ineffective. The darkness-induced increase in melatonin content in vitro was inhibited by bicuculline, whereas saclofen was ineffective. Retinal GABA turnover rate was significantly higher at midnight than at midday. GABA significantly decreased cyclic AMP and increased cyclic GMP accumulation in the golden hamster retina. The effect of GABA on both nucleotide levels was reversed by bicuculline, but baclofen had no effect. Cyclic GMP analogues (i.e., 8-bromoguanosine 3',5'-cyclic monophosphate and 2'-O-dibutyrylguanosine 3',5'-cyclic monophosphate) significantly increased retinal melatonin content in vitro. Taken together, these results support the hypothesis that GABA may be important for the "dark message" in the hamster retina.