Effect of Melatonin and Its Analogs on Tear Secretion

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dc.contributor.authorNavarro Gil, Francisco Javier
dc.contributor.authorHuete Toral, Fernando
dc.contributor.authorCrooke Álvarez, Almudena
dc.contributor.authorDomínguez Godínez, Carmen Olalla
dc.contributor.authorCarracedo Rodríguez, Juan Gonzalo
dc.contributor.authorPintor Just, Jesús Jerónimo
dc.date.accessioned2023-06-17T13:29:09Z
dc.date.available2023-06-17T13:29:09Z
dc.date.issued2019-10
dc.descriptionEn memoria de Jesús Pintor.
dc.description.abstractMelatonin 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.en
dc.description.departmentDepto. de Optometría y Visión
dc.description.departmentUnidad Docente de Bioquímica y Biología Molecular
dc.description.facultyFac. de Óptica y Optometría
dc.description.refereedTRUE
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/57108
dc.identifier.citationNavarro 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.
dc.identifier.doi10.1124/jpet.119.259192
dc.identifier.issn0022-3565 (Print), 1521-0103 (On line)
dc.identifier.officialurlhttps://doi.org/10.1124/jpet.119.259192
dc.identifier.relatedurlhttp://jpet.aspetjournals.org/content/371/1/186
dc.identifier.relatedurlhttp://jpet.aspetjournals.org/content/early/2019/08/01/jpet.119.259192
dc.identifier.relatedurlhttps://europepmc.org/abstract/med/31371479
dc.identifier.urihttps://hdl.handle.net/20.500.14352/13599
dc.issue.number1
dc.journal.titleThe Journal of pharmacology and experimental therapeutics
dc.language.isoeng
dc.page.final190
dc.page.initial186
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics
dc.relation.projectIDRD16/0008/0001
dc.rights.accessRightsrestricted access
dc.subject.cdu615.357:617.764
dc.subject.keywordMelatonin
dc.subject.keywordTranslational medicine
dc.subject.keywordTear secretion
dc.subject.keywordDry eye
dc.subject.ucmBioquímica (Biología)
dc.subject.ucmAnatomía ocular
dc.subject.unesco2302 Bioquímica
dc.titleEffect of Melatonin and Its Analogs on Tear Secretionen
dc.typejournal article
dc.volume.number371
dspace.entity.typePublication
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