Research paper
Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors

https://doi.org/10.1016/0006-2952(95)00109-DGet rights and content

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 Δ9-tetrahydrocannabinol (Δ9-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 Δ9-THC to inhibit electrically evoked contractions of mouse isolated vasa deferentia; however, it was less potent than Δ9-THC.

References (37)

  • NE Kaminski et al.

    Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid-mediated immune modulation

    Mol Pharmacol

    (1992)
  • M Bouaboula et al.

    Cannabinoid-receptor expression in human leukocytes

    Eur J Biochem

    (1993)
  • CM Gerárd et al.

    Molecular cloning of a human cannabinoid receptor which is also expressed in testis

    Biochem J

    (1991)
  • S Munro et al.

    Molecular characterization of a peripheral receptor for cannabinoids

    Nature

    (1993)
  • WA Devane et al.

    Isolation and structure of a brain constituent that binds to the cannabinoid receptor

    Science

    (1992)
  • L Hanuš et al.

    Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor

    J Med Chem

    (1993)
  • Z Vogel et al.

    Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase

    J Neurochem

    (1993)
  • CC Felder et al.

    Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction

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