RT Journal Article
T1 Effect of Melatonin and Its Analogs on Tear Secretion
A1 Navarro Gil, Francisco Javier
A1 Huete Toral, Fernando
A1 Crooke Álvarez, Almudena
A1 Domínguez Godínez, Carmen Olalla
A1 Carracedo Rodríguez, Juan Gonzalo
A1 Pintor Just, Jesús Jerónimo
AB 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.
PB American Society for Pharmacology and Experimental Therapeutics
SN 0022-3565 (Print), 1521-0103 (On line)
YR 2019
FD 2019-10
LK https://hdl.handle.net/20.500.14352/13599
UL https://hdl.handle.net/20.500.14352/13599
LA eng
NO 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.
NO En memoria de Jesús Pintor.
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 10 abr 2025