The search for the palmitoylethanolamide receptor

LoVerme, Jesse; Rana, Giovanna La; Russo, Roberto; Calignano, Antonio; Piomelli, Daniele

doi:10.1016/j.lfs.2005.05.012

Cited by 238 publications

(207 citation statements)

References 82 publications

Supporting

Mentioning

203

Contrasting

Order By: Relevance

“…1a). URB597 also increased hippocampal levels of the noncannabinoid fatty-acid ethanolamide palmitoylethanolamide (PEA) (26,27) while causing no acute or persistent increase in 2-AG content ( Fig. 1b; see also Table 1, which is published as supporting information on the PNAS web site).…”

Section: Resultsmentioning

confidence: 98%

Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis

Gobbi

Bambico

Mangieri

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

622

522

View full text Add to dashboard Cite

Although anecdotal reports suggest that cannabis may be used to alleviate symptoms of depression, the psychotropic effects and abuse liability of this drug prevent its therapeutic application. The active constituent of cannabis, Delta(9)-tetrahydrocannabinol, acts by binding to brain CB, cannabinoid receptors, but an alternative approach might be to develop agents that amplify the actions of endogenous cannabinoids by blocking their deactivation. Here, we show that URB597, a selective inhibitor of the enzyme fatty-acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test. Moreover, URB597 increases firing activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in the nucleus locus ceruleus. These actions are prevented by the CB, antagonist rimonabant, are accompanied by increased brain anandamide levels, and are maintained upon repeated URB597 administration. Unlike direct CB, agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of Delta(9)-tetrahydrocannabinol in rats. The findings support a role for anandamide in mood regulation and point to fatty-acid amide hydrolase as a previously uncharacterized target for antidepressant drugs

show abstract

Section: Resultsmentioning

confidence: 98%

Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis

Gobbi

Bambico

Mangieri

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

622

522

View full text Add to dashboard Cite

show abstract

“…N-Palmitoylethanolamine has anti-inflammatory (13)(14)(15), anti-nociceptive (16,17), immunosuppressive (18), neuroprotective (19), and antioxidant (20) effects. Recently, it was shown that the anti-inflammatory action of N-palmitoylethanolamine could be mediated by the activation of peroxisome proliferator-activated receptor-␣ (PPAR-␣) (21). Furthermore, N-oleoylethanolamine was shown to be anorexic via PPAR-␣ (22,23) and N-stearoylethanolamine to be pro-apoptotic (24) and anorexic (25).…”

mentioning

confidence: 99%

Molecular Characterization of N-Acylethanolamine-hydrolyzing Acid Amidase, a Novel Member of the Choloylglycine Hydrolase Family with Structural and Functional Similarity to Acid Ceramidase

Tsuboi

Sun

Okamoto

et al. 2005

Journal of Biological Chemistry

298

287

View full text Add to dashboard Cite

Bioactive N-acylethanolamines, including anandamide (an endocannabinoid) and N-palmitoylethanolamine (an anti-inflammatory and neuroprotective substance), are hydrolyzed to fatty acids and ethanolamine by fatty acid amide hydrolase. Moreover, we found another amidohydrolase catalyzing the same reaction only at acidic pH, and we purified it from rat lung (Ueda, N., Yamanaka, K., and Yamamoto, S. (2001) J. Biol. Chem. 276, 35552-35557). Here we report complementary DNA cloning and functional expression of the enzyme termed "N-acylethanolamine-hydrolyzing acid amidase (NAAA)" from human, rat, and mouse. The deduced primary structures revealed that NAAA had no homology to fatty acid amide hydrolase but belonged to the choloylglycine hydrolase family. Human NAAA was essentially identical to a gene product that had been noted to resemble acid ceramidase but lacked ceramide hydrolyzing activity. The recombinant human NAAA overexpressed in HEK293 cells hydrolyzed various N-acylethanolamines with N-palmitoylethanolamine as the most reactive substrate. Most interestingly, a very low ceramide hydrolyzing activity was also detected with NAAA, and N-lauroylethanolamine hydrolyzing activity was observed with acid ceramidase. By the use of tunicamycin and endoglycosidase, NAAA was found to be a glycoprotein. Furthermore, the enzyme was proteolytically processed to a shorter form at pH 4.5 but not at pH 7.4. Expression analysis of a green fluorescent protein-NAAA fusion protein showed a lysosome-like distribution in HEK293 cells. The organ distribution of the messenger RNA in rats revealed its wide distribution with the highest expression in lung. These results demonstrated that NAAA is a novel N-acylethanolamine-hydrolyzing enzyme that shows structural and functional similarity to acid ceramidase.

show abstract

“…For dogs and cats, the veterinarian-recommended, readymade hemp based supplement Canna-Pet is presently available (containing non-psychoactive cannabidiol). PEA can at present be used to restore skin reactivity in animals in a veterinary medication sold under the trade name Redonyl (LoVerme et al 2005). It is therefore not surprising that owners of animals are also exhibiting increasing interest in the possible use of cannabinoids/medical marijuana in veterinary medicine as can be seen by the number of internet forums concerned with this issue (e.g.…”

Section: Prospective Veterinary Use Of Cannabinoidsmentioning

confidence: 99%

The use of cannabinoids in animals and therapeutic implications for veterinary medicine: a review

Landa¹,

Šulcová²,

Gbelec³

2016

Vet. Med. - Czech

View full text Add to dashboard Cite

Cannabinoids/medical marijuana and their possible therapeutic use have received increased attention in human medicine during the last years. This increased attention is also an issue for veterinarians because particularly companion animal owners now show an increased interest in the use of these compounds in veterinary medicine. This review sets out to comprehensively summarise well known facts concerning properties of cannabinoids, their mechanisms of action, role of cannabinoid receptors and their classification. It outlines the main pharmacological effects of cannabinoids in laboratory rodents and it also discusses examples of possible beneficial use in other animal species (ferrets, cats, dogs, monkeys) that have been reported in the scientific literature. Finally, the article deals with the prospective use of cannabinoids in veterinary medicine. We have not intended to review the topic of cannabinoids in an exhaustive manner; rather, our aim was to provide both the scientific community and clinical veterinarians with a brief, concise and understandable overview of the use of cannabinoids in veterinary medicine.

show abstract

The search for the palmitoylethanolamide receptor

Cited by 238 publications

References 82 publications

Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis

Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis

Molecular Characterization of N-Acylethanolamine-hydrolyzing Acid Amidase, a Novel Member of the Choloylglycine Hydrolase Family with Structural and Functional Similarity to Acid Ceramidase

The use of cannabinoids in animals and therapeutic implications for veterinary medicine: a review

Contact Info

Product

Resources

About