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-ara chidonyl glycerol (2-Ara-Gl). Its structure was determined by mass spe ctrometry and by direct comparison with a synthetic sample. 2-Ara-Gl b ound to membranes from cells transiently transfected with expression p lasmids carrying DNA of either CB1 or CB2-the two cannabinoid receptor s identified thus far-with K-i values of 472 +/- 55 and 1400 +/- 172 n M, respectively. In the presence of forskolin, 2-Ara-Gl inhibited aden ylate cyclase in isolated mouse spleen cells, at the potency level of Delta(9)-tetrahydrocannabinol (Delta(9)-THC). Upon intravenous adminis tration to mice, 2-Ara-Gl caused the typical tetrad of effects produce d by THC: antinociception, immobility, reduction of spontaneous activi ty, and lowering of the rectal temperature. 2-Ara-Gl also shares the a bility of Delta(9)-THC to inhibit electrically evoked contractions of mouse isolated vasa deferentia; however, it was less potent than Delta (9)-THC.