Metabolism of Anandamide, an Endogenous Cannabinoid Receptor Ligand, in Porcine Ocular Tissues

doi:10.1006/exer.1996.0265

Experimental Eye Research

Volume 64, Issue 5, May 1997, Pages 707-711

https://doi.org/10.1006/exer.1996.0265 Get rights and content

Abstract

Anandamide (arachidonylethanolamide) is an endogenous ligand for cannabinoid receptors, and exerts various cannabimimetic activities. Since cannabinoids and anandamide were pharmacologically active with the eye, we examined metabolism of anandamide in a variety of porcine ocular tissues. In the presence of ethanolamine, [¹⁴C]arachidonic acid was converted to [¹⁴C]anandamide by a homogenate of retina, choroid, iris, optic nerve and lacrimal gland with a specific enzyme activity of 1.9–4.2 nmol min⁻¹mg⁻¹protein at 37°C. On the other hand, [¹⁴C]anandamide was hydrolysed to [¹⁴C]arachidonic acid by a homogenate of each tissue with a specific enzyme activity of 1.2–3.5 nmol min⁻¹mg⁻¹protein. Thus, both activities of anandamide synthase and hydrolase were found in these ocular tissues. As for the subcellular distribution, the two enzyme activities were mostly recovered in particulate fractions rather than the cytosol. With the retina microsome palmitic acid was converted to its ethanolamide at a lower rate than arachidonic acid, and palmitoylethanolamide was less active than anandamide as a substrate for the hydrolase.

References (0)

Cited by (84)

Topical application of cannabinoid-ligands ameliorates experimental dry-eye disease
2022, Ocular Surface
Dry eye disease (DED) is a multifactorial disease, with limitations regarding efficacy and tolerability of applied substances. Among several candidates, the endocannabinoid system with its receptors (CB1R and CB2R) were reported to modulate inflammation, wound healing and pain, which are also core DED pathomechanisms. This study is to investigate the therapeutic responses of Δ-9 tetrahydrocannabinol (a non-selective agonist) and two selective antagonists, SR141716A (CB1R antagonist) and SR144528 (CB2R antagonist), as a topical application using a DED mouse model.
Experimental DED was induced in naïve C57BL/6 mice. Expression of CBR at the ocular surface of naïve and DED mice was determined by qPCR and in-situ hybridization. Either THC or CBR antagonists were compounded in an aqueous solution and dosed during the induction of DED. Tear production, cornea sensitivity, and cornea fluorescence staining were tested. At the end of each experiment, corneas were stained with β3-tubulin for analysis of corneal nerve morphology. Conjunctiva was analyzed for CD4⁺ and CD8⁺ infiltration.
CB1R and CB2R are present at the ocular surface, and desiccating stress increased CBR expressions (p < 0.05). After 10 days of DED induction, treated groups demonstrated a reduced CBR expression in the cornea, which was concurrent with improvements in the DED phenotype including fluorescence staining & inflammation. Applying THC protected corneal nerve morphology, thus maintained corneal sensitivity and reduced CD4⁺ T-cell infiltration. The CB1R antagonist maintained cornea sensitivity without changing nerve morphology.
Endocannabinoid receptor modulation presents a potential multi-functional therapeutic approach for DED.
The cannabinoid system and visual processing: A review on experimental findings and clinical presumptions
2015, European Neuropsychopharmacology
Cannabis is one of the most prevalent drugs used worldwide. Regular cannabis use is associated with impairments in highly integrative cognitive functions such as memory, attention and executive functions. To date, the cerebral mechanisms of these deficits are still poorly understood. Studying the processing of visual information may offer an innovative and relevant approach to evaluate the cerebral impact of exogenous cannabinoids on the human brain. Furthermore, this knowledge is required to understand the impact of cannabis intake in everyday life, and especially in car drivers. Here we review the role of the endocannabinoids in the functioning of the visual system and the potential involvement of cannabis use in visual dysfunctions. This review describes the presence of the endocannabinoids in the critical stages of visual information processing, and their role in the modulation of visual neurotransmission and visual synaptic plasticity, thereby enabling them to alter the transmission of the visual signal. We also review several induced visual changes, together with experimental dysfunctions reported in cannabis users. In the discussion, we consider these results in relation to the existing literature. We argue for more involvement of public health research in the study of visual function in cannabis users, especially because cannabis use is implicated in driving impairments.
Cannabinoid applications in glaucoma
2011, Archivos de la Sociedad Espanola de Oftalmologia
El glaucoma es una neuropatía óptica lentamente progresiva que constituye una de las principales causas de ceguera legal en el mundo. Actualmente existe un limitado grupo de fármacos tópicos para su manejo médico, siendo necesario enfocar la investigación hacia nuevos horizontes terapéuticos como el potencialmente útil grupo de los agonistas de cannabinoides.
Revisar a través de la literatura científica actual, los efectos beneficiosos a través de distintas vías de administración de los cannabinoides para la neuropatía óptica glaucomatosa.
Los receptores de cannabinoides han demostrado una amplia expresión en los tejidos oculares implicados en la regulación de la tensión ocular, así como en las capas internas de la retina. Mediante la activación de receptores específicos CB1, CB2 y vías aún no bien conocidas, los agonistas de cannabinoides han demostrado un claro efecto hipotensor ocular, así como un probado efecto neuroprotector sobre las células ganglionares de la retina en estudios experimentales.
Algunos cannabinoides (WIN 55212-2, anandamida) han demostrado a nivel experimental actuar como «fármacos ideales» en el manejo del glaucoma, al presentar buena tolerancia tras su aplicación tópica, reducir de forma eficaz la presión intraocular, y presentar un probado carácter neuroprotector sobre las células ganglionares de la retina.
Se deben realizar más estudios sobre su seguridad y ensayos clínicos para poder examinar la utilidad de estos fármacos en el tratamiento del glaucoma en nuestra clínica diaria.
Glaucoma is a slowly progressive optic neuropathy that is one of the leading causes of legal blindness throughout the world. Currently there is a limited group of topical drugs for the medical treatment of glaucoma is currently limited, and research needs to be focused on new therapeutic horizons, such as the potential usefulness of the cannabinoid agonists for the treatment of glaucoma.
To review the current scientific literature related to the beneficial effects derived from the different ways of administration of cannabinoids indicated for the glaucomatous optic neuropathy.
Cannabinoid receptors have shown an intense expression in ocular tissues implicated in the regulation of the intraocular pressure, as well as inner layers of the retina. Through activation of CB1 and CB1 specific receptors and through other still unknown pathways, the cannabinoid agonists have shown both a clear hypotensive, as well as an experimentally proved neuroprotective effect on retinal ganglion cells.
Some cannabinoid agonists (WIN 55212-2, anandamide) have demonstrated, in experimental studies, to act as «ideal drugs» in the management of glaucoma, as they have been shown to have good tolerability after topical application, efficiently reduce intraocular pressure, and behave as neuroprotectors on retinal ganglion cells.
Further studies as regards the safety and clinical assays must be carried out in order to examine the effectiveness of these drugs for the treatment of glaucoma in our daily clinical practice.
Pain and beyond: fatty acid amides and fatty acid amide hydrolase inhibitors in cardiovascular and metabolic diseases
2009, Drug Discovery Today
Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of several important endogenous fatty acid amides (FAAs), including anandamide, oleoylethanolamide and palmitoylethanolamide. Because specific FAAs interact with cannabinoid and vanilloid receptors, they are often referred to as ‘endocannabinoids’ or ‘endovanilloids’. Initial interest in this area, therefore, has focused on developing FAAH inhibitors to augment the actions of FAAs and reduce pain. However, recent literature has shown that these FAAs – through interactions with unique receptors (extracellular and intracellular) – can induce a diverse array of effects that include appetite suppression, modulation of lipid and glucose metabolism, vasodilation, cardiac function and inflammation. This review gives an overview of FAAs and diverse FAAH inhibitors and their potential therapeutic utility in pain and non-pain indications.
Ontogenetic expression of the vanilloid receptors TRPV1 and TRPV2 in the rat retina
2009, International Journal of Developmental Neuroscience
Citation Excerpt :
Several reports have indicated that the mammalian retina presents all elements of the endocannabinoid/vanilloid machinery. The retina of different species can produce and hydrolyse anandamide, a cannabinoid CB1 and TRPV1 receptor agonist, as well as other endocannabinoids (Matsuda et al., 1997; Bisogno et al., 1999; Straiker et al., 1999a, 1999b; Yazulla et al., 1999; Straiker and Sullivan, 2003; Chen et al., 2005; Glaser et al., 2005). In the rat retina, 2-arachidonoylglycerol was found to be the main cannabinoid compound (Straiker et al., 1999a).
The present study aimed to analyze the gene and protein expression and the pattern of distribution of the vanilloid receptors TRPV1 and TRPV2 in the developing rat retina. During the early phases of development, TRPV1 was found mainly in the neuroblastic layer of the retina and in the pigmented epithelium. In the adult, TRPV1 was found in microglial cells, blood vessels, astrocytes and in neuronal structures, namely synaptic boutons of both retinal plexiform layers, as well as in cell bodies of the inner nuclear layer and the ganglion cell layer. The pattern of distribution of TRPV1 was mainly punctate, and there was higher TRPV1 labeling in the peripheral retina than in central regions. TRPV2 expression was quite distinct. Its expression was virtually undetectable by immunoblotting before P1, and that receptor was found by immunohistochemistry only by postnatal day 15 (P15). RNA and protein analysis showed that the adult levels are only reached by P60, which includes small processes in the retinal plexiform layers, and labeled cellular bodies in the inner nuclear layer and the ganglion cell layer. There was no overlapping between the signal observed for both receptors. In conclusion, our results showed that the patterns of distribution of TRPV1 and TRPV2 are different during the development of the rat retina, suggesting that they have specific roles in both visual processing and in providing specific cues to neural development.
Commercially Available Prostaglandin Analogs for the Reduction of Intraocular Pressure: Similarities and Differences
2008, Survey of Ophthalmology
Over the last 12 years, the pharmacological management of glaucoma and ocular hypertension has significantly changed with the introduction of the prostaglandin analogs, specifically, latanoprost, bimatoprost, and travoprost. Their ability to effectively reduce intraocular pressure with once-per-day dosing, their comparable ocular tolerability with timolol, and their general lack of systemic side effects have made them the mainstay of pharmacological therapy for glaucoma and ocular hypertension in most parts of the world. A review of their pharmacology reveals that they are all prodrugs that are converted to their respective free acids within the eye to activate the prostanoid FP receptor and to reduce intraocular pressure by enhancing the uveoscleral and the trabecular meshwork outflow pathways. A review of numerous prospective, randomized comparative studies indicates that no clinically significant differences exist among these agents regarding their ability to lower intraocular pressure.

View all citing articles on Scopus

^f1: Corresponding author: Shozo Yamamoto, Department of Biochemistry, Tokushima University, School of Medicine, Kuramoto-cho, Tokushima 770, Japan.

View full text

Regular articleMetabolism of Anandamide, an Endogenous Cannabinoid Receptor Ligand, in Porcine Ocular Tissues

Abstract

Regular article
Metabolism of Anandamide, an Endogenous Cannabinoid Receptor Ligand, in Porcine Ocular Tissues