Melatonin effect on the cyclic GMP system in the golden hamster retina

M. P. FAILLACE, M.I. KELLER SARMIENTO, AND R.E. ROSENSTEIN

Lyon

Workshop; Biological Rhythms : Physiological and Molecular Mechanisms, NSF-CNRS International Workshop on Chronobiology, March 9-12 1997, Lyon, France; 1997

NSF-CNRS

Melatonin effect on retinal cyclic GMP accumulation, guanylate cyclase activity, cyclic GMP content and cyclic GMP phosphodiesterase activity was examined in the Syrian hamster retina. Melatonin increased significantly cyclic GMP accumulation at picomolar concentrations and in a time-dependent manner. The kinetic analysis of guanylate cyclase activity revealed a significant increase of both apparent Vma,, and Kr, , induced by 10 nM melatonin. The effect of melatonin was higher in the absence, than in the presence of the phoshodiesterase inhibitor (IBMX), suggesting an effect on cyclic GMP catabolism. Phosphodiesterase activity was significantlydecreased by melatonin. The results show a dual effect of melatonin on cyclic GMP levels, i.e. by increasing the synthesis and inhibiting the degradation, both resulting in an increase of cyclic GMP levels. Taking into account the key role of cyclic GMP in visual mechanisms, the results would suggest the participation of melatonin in retinal physiology.Daily variations in cGMP, guanylate cyclase and phosphodiesterase activity in golden hamsterretina were studied. Cyclic GMP content exhibited significant variations throughout the 24.hr cyclewith maximal values during the dark phase. In order to establish the relative participation ofnucleotide synthesis and breakdown during a 24-hr cycle, guanylate cyclase and phosphodiesteraseactivity were measured in hamsters killed at eight intervals. Guanylate cyclase activity increased atnight, peaking at 22.00 hr. Phosphodiesterase activity did not change significantly throughout thelight-dark cycle. Light exposure during the night inhibited the nocturnal increase in cGMP contentand guanylate cyclase activity, while phosphodiesterase remained unchanged. From these results, itmight be presumed that in response to continuous (in a range of hr) light or dark stimuli, the retinawould process the photic signal in a different way from that in the short term (in a range of msec).