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Effect of Melatonin and Its Analogs on Tear Secretion

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Navarro Gil, Francisco Javier and Huete Toral, Fernando and Crooke, Almudena and Dominguez Godínez, Carmen Olalla and Carracedo Rodríguez, Juan Gonzalo and Pintor, Jesús (2019) Effect of Melatonin and Its Analogs on Tear Secretion. The Journal of pharmacology and experimental therapeutics, 371 (1). pp. 186-190. ISSN 0022-3565 (Print), 1521-0103 (On line)

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Official URL: https://doi.org/10.1124/jpet.119.259192




Abstract

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.


Item Type:Article
Additional Information:

En memoria de Jesús Pintor.

Uncontrolled Keywords:Melatonin; Translational medicine; Tear secretion; Dry eye;
Subjects:Medical sciences > Biology > Biochemistry
Medical sciences > Optics > Eyes anatomy
ID Code:57108
Deposited On:30 Sep 2019 12:20
Last Modified:30 Sep 2019 12:20

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