RESUMO
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.
Assuntos
Dopamina/farmacologia , Melatonina/metabolismo , Retina/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Benzazepinas/farmacologia , Cromatografia Líquida de Alta Pressão , Ritmo Circadiano/fisiologia , Clozapina/farmacologia , Cricetinae , AMP Cíclico/metabolismo , Depressão Química , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Cinética , Masculino , Mesocricetus , Quimpirol/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacos , Retina/efeitos dos fármacos , Espiperona/farmacologiaRESUMO
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.
Assuntos
Melatonina/metabolismo , Retina/metabolismo , Ácido gama-Aminobutírico/farmacologia , 1-Metil-3-Isobutilxantina/farmacologia , Animais , Bicuculina/farmacologia , Cricetinae , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Escuridão , Relação Dose-Resposta a Droga , Antagonistas GABAérgicos/farmacologia , Masculino , MesocricetusRESUMO
A characterization of nitric oxide synthase (NOS) in the golden hamster retina was performed. Enzymatic activity was partially Ca2+ and calmodulin-dependent, required NADPH, and was inhibited by L-arginine analogs. Retinal NOS activity was higher at midnight than at midday. When the hamster were placed under constant darkness for 24 or 48 h, and killed at equivalent time points, representing subjective day and subjective night respectively, the differences in NOS activity disappeared. One hour of darkness during the day increased, while the same period of light during the night decreased, retinal NOS activity. From these results, it might be presumed that hamster retinal NOS activity is regulated by the photic stimulus.