Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.
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.
Mechoulam
R
R
Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Ben-Shabat
S
S
Hanus
L
L
Ligumsky
M
M
Kaminski
N E
NE
Schatz
A R
AR
Gopher
A
A
Almog
S
S
Martin
B R
BR
Compton
D R
DR
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*
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D005989:Glycerides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C094503:glyceryl 2-arachidonate