Inhibitory modulation of photoreceptor melatonin synthesis via a nitric oxide-mediated mechanism.
Nitric oxide (NO) has been suggested to have many physiological functions in the vertebrate retina, including a role in light-adaptive processes. The aim of this study was to examine the influence of the NO-donor sodium nitroprusside (SNP) on the activity of arylalkylamine-N-acetyltransferase (AA-NAT; EC. 2.3.1.87), the activity of which responds to light and reflects the changes in retinal melatonin synthesis--a key feature of light-adaptive responses in photoreceptors. Incubation of dark-adapted and dark-maintained retinas with SNP lead to the NO-specific suppression of AA-NAT activity, with NO suppressing AA-NAT activity to a level similar to that seen in the presence of dopaminergic agonists or light. Increased levels of cGMP appeared to be causally involved in the suppression of AA-NAT activity by SNP, as non-hydrolysable analogues of cGMP and the cGMP-specific phosphodiesterase (PDE) inhibitor zaprinast also significantly suppressed AA-NAT activity, while an inhibitor of soluble guanylate cyclase blocked the effect of SNP. While this chain of events may not be part of the normal physiology of the retina, it could be important in pathological circumstances that are associated with marked increase in levels of cGMP, as is found to be the case in certain forms photoreceptor degeneration, which are produced by defects in cGMP phosphodiesterase activity.
Wellard
John W
JW
Visual Sciences Group, Research School of Biological Sciences, The Australian National University, GPO Box 475, Canberra ACT 2601, Australia.
Morgan
Ian G
IG
D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000378:metabolism; D002645:Chickens; D006152:Cyclic GMP / Q000096:biosynthesis; D003623:Dark Adaptation / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D004745:Enkephalins / Q000502:physiology; D007267:Injections; D007700:Kinetics; D008550:Melatonin / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000201:enzymology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014822:Vitreous Body
D018491:Dopamine Agonists; D004745:Enkephalins; D020030:Nitric Oxide Donors; D013764:Tetrahydronaphthalenes; D009599:Nitroprusside; D009569:Nitric Oxide; C011639:ADTN; D047068:Arylalkylamine N-Acetyltransferase; D006152:Cyclic GMP; D008550:Melatonin; D004298:Dopamine