Sympathetic nervous system modulates the ocular hypotensive action of MT sub(2)-melatonin receptors in normotensive rabbits

The aim of this study was to investigate the hypotensive effect of the melatonin analogue, N-butanoyl-2-(2-methoxy-6H-isoindolo[2,1-a]indol-11-yl)ethan amine (IIK7), through MT sub(2)-melatonin receptors and the involvement of the sympathetic nervous system in this action in New Zealand rabbit eyes. The topical application of melatonin or IIK7 produced a reduction in intraocular pressure of 20.2 plus or minus 5.3% and 38.5 plus or minus 3.2% respectively. This effect was concentration-dependent; it was blocked by selective MT sub(2) receptor antagonists and was severely diminished after chemical sympathectomy. Immunohistochemistry and western blot analysis showed the ciliary processes as the site of this action and no co-localization of MT sub(2)-melatonin receptor with the sympathetic nervous system was observed. The beta -adrenergic agonists, terbutaline and salbutamol, potentiated the hypotensive effect of IIK7 reducing intraocular pressure (IOP) 41.75 plus or minus 4.26% and 44.7 plus or minus 5.6% respectively. Also, IIK7 in presence of the nonspecific protein phosphatase inhibitor okadaic acid, lowered IOP 32.2 plus or minus 4.5% and in presence of forskolin plus 3-isobutyl-1-methylxanthine decreased IOP in 32.2 plus or minus 5.47%. These data suggest that the melatonin agonist IIK7 reduces intraocular pressure by acting through MT sub(2)-melatonin receptors presumably decreasing aqueous humour formation. Also, in the presence of beta -adrenoceptor agonists MT sub(2)-melatonin receptors activity increase their ability to reduce IOP.