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 arylalkymine N-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.

Melatonin and the control of intraocular pressure

“…these cells are able to produce the indolamine (Fig. 6) (Alkozi et al, 2017c). A small interference siRNA approach confirmed that all those effects are mediated by TRPV4 (Alkozi et al, 2017b).…”

“…Values represent the mean ± SEM (n = 6; *p < 0.05, **p < 0.01, ***p < 0.001 versus time 0). Taken from (Alkozi et al, 2017c(Alkozi et al, : open access). 1928).…”

The Role and Therapeutic Potential of Melatonin in Degenerative Fundus Diseases: Diabetes Retinopathy and Age-Related Macular Degeneration

“…Likewise, darkness increases AANAT expression and melatonin production in lens epithelial cells. 67 Lenses are transparent tissues inside the eyes used for focusing light. 68 Oxidative stress and inflammatory responses affect lens clarity and function.…”

Expression of Melatonin and Dopamine D3 Receptor Heteromers in Eye Ciliary Body Epithelial Cells and Negative Correlation with Ocular Hypertension

“…We wondered whether intraocular hypertension correlated with the altered expression of dopamine and melatonin heteroreceptor complexes. First of all, we took advantage of an in vitro model of hypertension, described in Reference [54], consisting of the activation of the transient Interestingly, and as previously described by Alkozi et al, [34], none of the melatonin receptor agonists, melatonin or IIK7, were able to decrease cAMP levels in these cells. Next, we analyzed ERK1/2 phosphorylation, which was significantly enhanced when 7-OH-PIPAT was added ( Figure 4B,E).…”

“…We wondered whether intraocular hypertension correlated with the altered expression of dopamine and melatonin heteroreceptor complexes. First of all, we took advantage of an in vitro model of hypertension, described in Reference [54], consisting of the activation of the transient receptor potential vanilloid 4 (TRPV4) channel. Such activation in 59HCE cells using GSK1016790A mimics the ion fluxes that drive the increase in hydrostatic pressure that occurs in the hypertensive/glaucomatous eye.…”