title: Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.
abstract: In this study, we report the isolation from canine intestines of 2-arachidonyl glycerol (2-Ara-Gl). Its structure was determined by mass spectrometry and by direct comparison with a synthetic sample. 2-Ara-Gl bound to membranes from cells transiently transfected with expression plasmids carrying DNA of either CB1 or CB2--the two cannabinoid receptors identified thus far--with Ki values of 472 +/- 55 and 1400 +/- 172 nM, respectively. In the presence of forskolin, 2-Ara-Gl inhibited adenylate cyclase in isolated mouse spleen cells, at the potency level of delta 9-tetrahydrocannabinol (delta 9-THC). Upon intravenous administration to mice, 2-Ara-Gl caused the typical tetrad of effects produced by THC: antinociception, immobility, reduction of spontaneous activity, and lowering of the rectal temperature. 2-Ara-Gl also shares the ability of delta 9-THC to inhibit electrically evoked contractions of mouse isolated vasa deferentia; however, it was less potent than delta 9-THC.
authors.affiliation: Faculty of Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Mechoulam
authors.forename: S
authors.initials: S
authors.lastname: Ben-Shabat
authors.forename: L
authors.initials: L
authors.lastname: Hanus
authors.forename: M
authors.initials: M
authors.lastname: Ligumsky
authors.forename: N E
authors.initials: NE
authors.lastname: Kaminski
authors.forename: A R
authors.initials: AR
authors.lastname: Schatz
authors.forename: A
authors.initials: A
authors.lastname: Gopher
authors.forename: S
authors.initials: S
authors.lastname: Almog
authors.forename: B R
authors.initials: BR
authors.lastname: Martin
authors.forename: D R
authors.initials: DR
authors.lastname: Compton
mesh_terms: D000818:Animals; D001095:Arachidonic Acids; D002186:Cannabinoids / Q000819:agonists; D002460:Cell Line; D004285:Dogs; D063388:Endocannabinoids; D008401:Gas Chromatography-Mass Spectrometry; D005989:Glycerides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007422:Intestines / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D005989:Glycerides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C094503:glyceryl 2-arachidonate