Vanilloid receptor 1 (TRPV1/VR1) co-localizes with fatty acid amide hydrolase (FAAH) in retinal amacrine cells

Abstract

Fatty acid amide hydrolase (FAAH) is the degradative enzyme for anandamide (AEA), an endogenous ligand for the vanilloid receptor (TRPV1) and cannabinoid receptor 1. As FAAH and TRPV1 are integral membrane proteins, FAAH activity could modulate the availability of AEA for TRPV1 activation. Previous studies in this laboratory reported an extensive endocannabinoid system in goldfish retina. Immunocytochemistry was used to determine the relative distributions of FAAH-immunoreactivity (IR) and TRPV1-IR in goldfish retina. Here, we show the first example in an intact neural system in which TRPV1-IR co-localizes in subpopulations of FAAH-immunoreactive neurons, in this case amacrine cells. These cells are rare and consist of three subtypes: 1. ovoid cell with granular-type dendrites restricted to sublamina a, 2. pyriform cell with smooth processes in sublamina b, and 3. fusiform cell with smooth processes that project to sublaminae a and b. The varied appearances of reaction product in the dendrites suggest different subcellular localization of TRPV1, and hence function of FAAH activity regarding TRPV1 stimulation among the cell types. Ovoid and pyriform amacrine cells, but not fusiform cells, labeled with GAD-IR and constituted subsets of GABAergic amacrine cells. TRPV1 amacrine cells, though rare, are represented in the ON, OFF and ON/OFF pathways of the retina. As TRPV1 stimulation increases intracellular calcium with numerous downstream effects, co-localization of TRPV1 and FAAH suggests an autoregulatory function for anandamide. Due to the rarity of these cells, the three vanilloid amacrine cell types may be involved in global effects rather than feature extraction, for example: sampling of ambient light or maintaining homeostasis.

In the Heat of the Night: Thermo-TRPV Channels in the Salmonid Pineal Photoreceptors and Modulation of Melatonin Secretion

“…We may speculate that the TRPVs expressed in the synaptic pedicles of the pineal photoreceptors are involved in the regulation of the described effects of temperature on the nervous discharges of the trout pineal neurons (2). We also found that TRPV1 and TRPV4 were expressed in the INL of the trout retina, as is the case in zebrafish (36,42). In contrast the GCL of trout expressed TRPV1 only, while the opposite was found in the zebrafish.…”

Role of ionotropic cannabinoid receptors in peripheral antinociception and antihyperalgesia

“…Cannabinoids can also be coupled to G q/11 proteins [54,55], and this could lead to activation of the phospholipase C pathway which, in turn, could result in the activation of several TRP channels including TRPA1 [56]. In addition, fatty acid amine hydrolase (FAAH) is involved in anandamide metabolism and is co-localized with TRPV1 in several areas, indicating an important regulatory interaction [57]. Indeed, inhibition of FAAH rapidly leads to accumulation of fatty acid amides, some of which are efficacious TRP agonists [58].…”

Transient receptor potential cation channel, subfamilies V, member 1 (TRPV1) and M, member 1 (TRPM1) contribute to neural signaling in mouse retina.

“…Previous publications report TRPV1 protein expression in the inner retina of rodents (Sappington et al, 2009& Leonelli et al, 2009& 2013, goldfish (Zimov &Yazulla, 2007), and non-human primates (Sappington et al, 2015). Similar to the role of TRPV1 in the PNS, the protein is thought to regulate Ca 2+ in the ganglion cell layer (GCL) and inner nuclear layer (INL) of the retina (Sappington et al, 2009(Sappington et al, & 2015Leonelli et al, 2010;Ryskamp et al, 2014).…”

“…TRPV1 is activated by endocannabinoids and endovanilloids such as anandamide, 12-Hepete, and NADA (see Ryskamp et al, 2014 for a review). Endovanilloids are synthesized from membrane phospholipids and cannot be immuno-labeled directly, but anandamide regulating enzymes have been localized to ACs in the goldfish and rat retina (Zimov & Yazulla, 2007;Hu et al, 2010;Zabouri et al, 2011). Interestingly, ACs expressing the regulatory enzyme FAAH in the goldfish retina co-localize with TRPV1-ir.…”

“…A few studies have looked at the localization of TRPV1 in the retina using antibodies, but results vary and although it is clear that TRPV1 mRNA and protein are present in the retina the specific cell types that express the TRPV1 remain unknown (Gilliam & Wensel, 2011). In goldfish, TRPV1-like channels are reported to be expressed in cone terminals (Zimov & Yazulla 2007). TRPV1…”