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oai:docta.ucm.es:20.500.14352/135992024-07-02T14:38:28Zcom_20.500.14352_14col_20.500.14352_15

Navarro Gil, Francisco Javier Huete Toral, Fernando Crooke Álvarez, Almudena Domínguez Godínez, Carmen Olalla Carracedo Rodríguez, Juan Gonzalo Pintor Just, Jesús Jerónimo 2023-06-17T13:29:09Z 2023-06-17T13:29:09Z 2019-10 Navarro Gil, F. J., Huete Toral, F., Crooke Álvarez, A. et al. «Effect of Melatonin and Its Analogs on Tear Secretion». Journal of Pharmacology and Experimental Therapeutics, vol. 371, n.o 1, octubre de 2019, pp. 186-90. DOI.org (Crossref), https://doi.org/10.1124/jpet.119.259192. 0022-3565 (Print), 1521-0103 (On line) 10.1124/jpet.119.259192 https://hdl.handle.net/20.500.14352/13599 https://doi.org/10.1124/jpet.119.259192 http://jpet.aspetjournals.org/content/371/1/186 http://jpet.aspetjournals.org/content/early/2019/08/01/jpet.119.259192 https://europepmc.org/abstract/med/31371479 Melatonin has been shown to enhance tear secretion associated with dinucleotide diadenosine tetraphosphate. This study investigated the isolated action of melatonin and its analogs, agomelatine, N-butanoyl-2-(2-methoxy-6H-isoindolo[2,1-a]indol-11-yl) ethanamine (IIK7), and 5-methoxycarbonylamino-N-cetyltryptamine (5-MCA-NAT) (10 µl at 100 µM), on tear secretion when applied topically in the rabbit cornea and its relationship with the melatonin MT1, MT2, and MT3/quinone reductase QR2 receptors. The results showed a significant increase in tear secretion, with a maximal effect at 60 minutes for the agonists (138.9% ± 6.5%, 128.9% ± 6.4%, and 120.0% ± 5.2%, respectively; P < 0.05; 100% control) but not for melatonin (101.6% ± 7.9%; P > 0.05). Agonist action was tested combined with the antagonists DH97 (MT2 selective), prazosin (MT3/QR2 inhibitor), and luzindole (nonselective MT membrane receptor) (10 µl at 100 µM). DH97 reversed the effect of agomelatine, IIK7, and 5-MCA-NAT up to 30.85% ± 7.6%,108% ± 7.2%, and 87.01% ± 7.6%, respectively (P < 0.05; 100% control). Luzindole antagonized agomelatine and 5-MCA-NAT up to 67.35% ± 7.6% and 92.12% ± 8%, respectively (P < 0.05). Prazosin only reversed 5-MCA-NAT action up to 84.2% ± 7.7% (P < 0.05). These results suggest different pathways for the agonists to act through MT membrane receptors. Therefore, agomelatine, IIK7, and 5-MCA-NAT act through MT membrane receptors as secretagogues of tear secretion, and these analogs could be considered excellent therapeutic candidates for dry eye treatment. eng restricted access Effect of Melatonin and Its Analogs on Tear Secretion journal article