Melatonin is currently considered as a promising drug for glaucoma treatment due to its ocular hypotensive and neuroprotective effects. We have investigated the effect of melatonin and its analogue 5-methoxycarbonylamino-N-acetyltryptamine, 5-MCA-NAT, on β2/α2A-adrenergic receptor mRNA as well as protein expression in cultured rabbit non-pigmented ciliary epithelial cells. Quantitative PCR and immunocytochemical assays revealed a significant β2-adrenergic receptor down-regulation as well as α2A-adrenergic receptor up-regulation of treated cells (p<0.001, maximal significant effect). In addition, we have studied the effect of these drugs upon the ocular hypotensive action of a non-selective β-adrenergic receptor (timolol) and a selective α2-adrenergic receptor agonist (brimonidine) in normotensive rabbits. IOP experiments showed that the administration of timolol in rabbits pre-treated with melatonin or 5-MCA-NAT evoked an additional IOP reduction of 14.02 ± 5.8 % or 16.75 ± 5.48 % (p<0.01) in comparison with rabbits treated with timolol alone for 24 hours. Concerning brimonidine hypotensive action, an additional IOP reduction of 29.26 ± 5.21 % or 39.07 ± 5.81 % (p<0.001) was observed in rabbits pretreated with melatonin or 5-MCA-NAT when compared with animals treated with brimonidine alone for 24 hours. Additionally, a sustained potentiating effect of a single dose of 5-MCA-NAT was seen in rabbits treated with brimonidine once daily for up four days (extra IOP decrease of 15.57 ± 5.15%, p<0.05, compared to brimonidine alone). These data confirm the indirect action of melatoninergic compounds on adrenergic receptors and their remarkable effect upon the ocular hypotensive action mainly of α2-adrenergic receptor agonists but also of β-adrenergic antagonists.
- The American Society for Pharmacology and Experimental Therapeutics