Melatonin effect on the cyclic GMP system in the golden hamster retina (original) (raw)
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EFFECTS OF LIGHT ON CYCLIC GMP METABOLISM IN RETINAL PHOTORECEPTORS
Journal of Neurochemistry, 1976
Abstract— Guanylate cyclase activity of dark-adapted bovine rod outer segments demonstrates a biphasic pattern upon exposure to light. By 10 s of illumination, activity is 20% lower than that observed in dark-adapted outer segments. Activity subsequently increases and then slowly declines to two-thirds of the original activity after 10 min of illumination. In the presence of GTP or ATP, hydrolysis of cyclic GMP is rapidly enhanced by exposure of outer segments to light; the magnitude of this effect is dependent on the amount of substrate present. The rapid effects of light on synthesis and degradation of cyclic GMP indicate that these reactions may be involved in the visual process. The concentration of guanosine 3′:5′-cyclic monophosphate (cyclic GMP) is extraordinarily high in dark-adapted bovine rod outer segments and is at least 100-fold that of adenosine 3′:5′-cyclic monophosphate (cyclic AMP). No significant decrease in the level of cyclic GMP or cyclic AMP was observed however upon exposure of dark-adapted outer segments to light.
Search for a physiological role of cyclic GMP metabolism in the photoreceptors
Neurochemistry International, 1980
Data on the time-course of the light-activation of the cyclic GMP phosphodiesterase and of the GTPase, and results on the influence of cyclic GMP on the disc membrane permeability are presented. On the basis of the kinetic data, it is not possible to separate the light-activation of these two enzymes from the early steps of photoreceptor transduction. In addition, the cyclic GMP increases the permeability of the disc membranes, indicating that a decrease of the endogenous cyclic GMP concentration, consequent to the light-activation of the phosphodiesterase, can de~ crease the membrane permeability shortly after illumination.
Journal of Neurochemistry, 1977
The effect of light on the content of cyclic GMP in degenerative retinae of Royal College of Surgeons (RCS) rats and rd mice was compared with that in control retinae during postnatal maturation. In vivo, the cyclic GMP content of retinae of control rats or mice is light-dependent after photoreceptor outer segments develop. Mature retinae of control animals have high levels of cyclic GMP in the dark which are reduced &50% upon illumination. In the rd mouse disorder, a lightinduced reduction in cyclic GMP content is observed while the rod outer segments are morphologically intact. The rd photoreceptor cells possess a phosphodiesterase which, when stabilized by freeze-drying, has a K , similar to that of control photoreceptors, and an apparent V,,, that is below normal. It is suggested that developing rd visual cells have an abnormality in cyclic GMP metabolism which results in the accumulation of cyclic GMP within the entire cell but which does not prevent the light-mediated reduction of cyclic GMP in their outer segment organelles. In the RCS dystrophy, a light-induced reduction in cyclic GMP content is observed also during the period when photoreceptor outer segments are present. The cyclic GMP content of dark-or light-adapted RCS retinae is below that of the respective controls. Biochemical and morphological observations show that cyclic GMP levels increase in rd visual cells and that they are reduced in photoreceptor cells of RCS retina before the onset of visual cell degeneration. Until detailed knowledge of the role of cyclic GMP in the visual cells is known, it is suggested that high or low levels of cyclic GMP in rd and RCS photoreceptors, respectively, result from differences in the etiology or histopathology of the mouse and rat diseases.
Cyclic GMP-phosphodiesterase of rd retina: Biosynthesis and content
Experimental Eye Research, 1988
Deficient cGMP-phosphodiesterase (cGMP-PDE) activity results in elevated levels of cGMP in the rd retina before any pathological signs are observed. Since the enzyme is present in rd retina, although it is barely activated by light, we determined whether its synthesis starts at the same time as that of cGMP-PDE in normal retina, or if either its synthesis is halted or degradation of the enzyme increases before the degeneration of the visual cells. We found that synthesis of cGMP-PDE in rd retina is comparable with that in normal retina while the photoreceptors are viable but that cGMP-PDE content is lower than that of normal retina before the visual cells begin to degenerate. Our results suggest that cGMP-PDE is more susceptible to degradation in rd than in normal photoreceptors or, alternatively, that proteolytic enzyme(s) involved in the degradation of cGMP-PDE are in higher concentration or more active in the defective than in the normal retina.
Melatonin: An underappreciated player in retinal physiology and pathophysiology
Experimental Eye Research, 2012
In the vertebrate retina, melatonin is synthesized by the photoreceptors with high levels of melatonin at night and lower levels during the day. Melatonin exerts its influence by interacting with a family of Gprotein-coupled receptors that are negatively coupled with adenylyl cyclase. Melatonin receptors belonging to the subtypes MT 1 and MT 2 have been identified in the mammalian retina. MT 1 and MT 2 receptors are found in all layers of the neural retina and in the retinal pigmented epithelium. Melatonin in the eye is believed to be involved in the modulation of many important retinal functions; it can modulate the electroretinogram (ERG), and administration of exogenous melatonin increases lightinduced photoreceptor degeneration. Melatonin may also have protective effects on retinal pigment epithelial cells, photoreceptors and ganglion cells. A series of studies have implicated melatonin in the pathogenesis of age-related macular degeneration, and melatonin administration may represent a useful approach to prevent and treat glaucoma. Melatonin is used by millions of people around the world to retard aging, improve sleep performance, mitigate jet lag symptoms, and treat depression. Administration of exogenous melatonin at night may also be beneficial for ocular health, but additional investigation is needed to establish its potential.
Journal of Neurochemistry, 2006
Various parameters of the rat pineal gland display a 24-h rhythm. However, nothing is known about possible 24-h variations in cyclic GMP (cGMP) metabolism. In the present study, 24-h variations in pineal gland cGMP accumulation were investigated by determining the increase in cGMP level with and without inhibitors of phosphodiesterase at different time points over a light/dark cycle (I2/ 12 h). Furthermore, the activity of guanylate cyclase (GC) was determined under substrate-saturated conditions regarding the cytosolic and particulate forms of the enzyme. It has been found that cGMP accumulation and GC activity display biphasic 24-h variations with two peaks-one-7 h after lights "on" and the other-7 h after lights "off." The activity of cytosolic GC remains unchanged in the presence of the nitric oxide (NO) synthesis inhibitor N-monomethyl-L-arginine, indicating that 24-h variations in the activity do not reflect changes in the synthesis of the GC stimulator NO. Key Words: Rat pineal gland-Light/dark cycle-Cyclic GMP-Cytosolic and particulate guan ylate cyclase. Spessert R. et al. Biphasic 24-hour variations in cyclic GMP accumulation in the rat pineal gland are due to corresponding changes in the activity of cytosolic and particulate guanylate cyclase.
Effect of GABA on Melatonin Content in Golden Hamster Retina
Journal of Neurochemistry, 2008
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, receptor antagonist, bicuculline, but not by saclofen, a GABA, antagonist. Moreover, an equimolar concentration of muscimol, a GABA, receptor agonist, significantly increased retinal melatonin content, whereas baclofen, a GABA, receptor agonist, was ineffective. The darknessinduced 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'-0dibutyrylguanosine 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.