title: TRPV4 Stimulation Induced Melatonin Secretion by Increasing Arylalkymine N-acetyltransferase (AANAT) Protein Level.
abstract: Melatonin is a molecule which has gained a great deal of interest in many areas of science; its synthesis was classically known to be in the pineal gland. However, many organs synthesize melatonin, such as several ocular structures. Melatonin is known to participate in many functions apart from its main action regulating the circadian rhythm. It is synthesized from serotonin in two steps, with a rate-limiting step carried out by arylalkymineN-acetyltransferase (AANAT). In this report, the role of TRPV4 channel present in human ciliary body epithelial cells in AANAT production was studied. Several experiments were undertaken to verify the adequate time to reach the maximal effect by using the TRPV4 agonist GSK1016790A, together with a dose-response study. An increase of 2.4 folds in AANAT was seen after 18 h of incubation with 10 nM of GSK1016790A (p< 0.001,n= 6). This increment was verified by antagonist assays. In summary, AANAT levels and therefore melatonin synthesis change after TRPV4 channel stimulation. Using this cell model together with human ciliary body tissue it is possible to suggest that AANAT plays an important role in pathologies related to intraocular pressure.
authors.affiliation: Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, University Complutense of Madrid, 28040 Madrid, Spain. Hanan-q1@live.com.
authors.forename: Hanan Awad
authors.initials: HA
authors.lastname: Alkozi
authors.affiliation: Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, University Complutense of Madrid, 28040 Madrid, Spain. mariajpdl@opt.ucm.es.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Perez de Lara
authors.affiliation: Department of Ophthalmology, Balear Institut of Ophthalmology, 07011 Palma de Mallorca, Spain. juansanchez.naves@gmail.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Sánchez-Naves
authors.affiliation: Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, University Complutense of Madrid, 28040 Madrid, Spain. jpintor@ucm.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pintor
mesh_terms: D047068:Arylalkylamine N-Acetyltransferase / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002924:Ciliary Body / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008550:Melatonin / Q000378:metabolism*; D018613:Microscopy, Confocal; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
chemical_list: C530602:N-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamide; C544743:RN 1734; D013449:Sulfonamides; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D012701:Serotonin; C478879:AANAT protein, human; D047068:Arylalkylamine N-Acetyltransferase; D007930:Leucine; D008550:Melatonin; C006389:N-acetylserotonin
keywords: AANAT; TRPV4; ciliary body; eye; melatonin