Article ID Journal Published Year Pages File Type
6197312 Experimental Eye Research 2013 10 Pages PDF
Abstract

The present study was designed to determine the effects of melatonin and its receptor agonists on SNP-released nitric oxide (NO) and cGMP production in aqueous humor producing cells of the ciliary body because these effects may play a role in melatonin receptor-mediated regulation of intraocular pressure (IOP). NO release protocols were carried out using human non-pigmented ciliary epithelial (hNPCE) cells treated in dye free DMEM containing l-arginine (10−3 M). The cGMP experimental protocols were performed using dye free DMEM containing 3-isobutyl-1-methylxanthine (IBMX, 10−4 M). The effects of varying concentrations (10−13, 10−11, 10−9, 10−7, and 10−5 M) of melatonin, 5-MCA-NAT (putative MT3 agonist), N-butanoyl-2-(2-methoxy-6H-isoindolo[2, 1-a]indol-11-yl)ethanamine (IIK7; selective MT2 agonist) or S-27633-1 (selective MT1 agonist) on sodium nitroprusside (SNP)-released NO or cGMP production were determined in separate experiments. NO and cGMP levels were measured using a colorimetric assay or enzyme immunoassay (EIA), respectively. Melatonin receptor selectivity was evaluated using luzindole (LUZ; nonselective MT1/MT2 antagonist) or 4-phenyl-2-propionamidotetralin (4P-PDOT; selective MT2 antagonist). Melatonin, 5-MCA-NAT, and IIK7 all caused concentration-dependent reduction of SNP-released NO and cGMP production. The inhibitory actions of melatonin, 5-MCA-NAT and IIK7 were either completely blocked at 10−13, 10−11, and 10−9 M concentrations of the agonists or partially at 10−7 and 10−5 M in the presence of luzindole or 4P-PDOT. Results from this study suggest that melatonin and its analogs, 5-MCA-NAT and IIK7 inhibit SNP-released NO and cGMP production via activation of MT2 receptors in human NPCE cells. These actions may play a role in melatonin agonist-induced regulation of aqueous humor secretion and IOP.

► We demonstrate the functional presence of MT2 melatonin receptors in hNPCE cells. ► Melatonin and its congeners inhibit NO release and cGMP production in hNPCE cells. ► Possible role of melatonin receptors in the regulation of aqueous humor secretion.

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