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

Raphael Mechoulam; Shimon Ben-Shabat; Lumir Hanus; Moshe Ligumsky; Norbert E. Kaminski; Anthony R. Schatz; Asher Gopher; Shlomo Almog; Billy R. Martin; David R. Compton; Roger G. Pertwee; Graeme Griffin; Michael Bayewitch; Jacob Barg; Zvi Vogel

doi:10.1016/0006-2952(95)00109-D

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

Raphael Mechoulam, Shimon Ben-Shabat, Lumir Hanus, Moshe Ligumsky, Norbert E. Kaminski, Anthony R. Schatz, Asher Gopher, Shlomo Almog, Billy R. Martin, David R. Compton, Roger G. Pertwee, Graeme Griffin, Michael Bayewitch, Jacob Barg, Zvi Vogel

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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 K_i 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.

Original language	English
Pages (from-to)	83-90
Number of pages	8
Journal	Biochemical Pharmacology
Volume	50
Issue number	1
DOIs	https://doi.org/10.1016/0006-2952(95)00109-D
State	Published - 29 Jun 1995
Externally published	Yes

Keywords

2-arachidonyl glycerol
adenylate cyclase inhibition
anandamide
arachidonylethanolamide
immune system
mouse behavior
tetrahydrocannabinol
transfection

ASJC Scopus subject areas

Biochemistry
Pharmacology

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10.1016/0006-2952(95)00109-D

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Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N. E., Schatz, A. R., Gopher, A., Almog, S., Martin, B. R., Compton, D. R., Pertwee, R. G., Griffin, G., Bayewitch, M., Barg, J., & Vogel, Z. (1995). Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochemical Pharmacology, 50(1), 83-90. https://doi.org/10.1016/0006-2952(95)00109-D

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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 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.",

keywords = "2-arachidonyl glycerol, adenylate cyclase inhibition, anandamide, arachidonylethanolamide, immune system, mouse behavior, tetrahydrocannabinol, transfection",

author = "Raphael Mechoulam and Shimon Ben-Shabat and Lumir Hanus and Moshe Ligumsky and Kaminski, \{Norbert E.\} and Schatz, \{Anthony R.\} and Asher Gopher and Shlomo Almog and Martin, \{Billy R.\} and Compton, \{David R.\} and Pertwee, \{Roger G.\} and Graeme Griffin and Michael Bayewitch and Jacob Barg and Zvi Vogel",

year = "1995",

month = jun,

day = "29",

doi = "10.1016/0006-2952(95)00109-D",

language = "English",

volume = "50",

pages = "83--90",

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Mechoulam, R, Ben-Shabat, S, Hanus, L, Ligumsky, M, Kaminski, NE, Schatz, AR, Gopher, A, Almog, S, Martin, BR, Compton, DR, Pertwee, RG, Griffin, G, Bayewitch, M, Barg, J & Vogel, Z 1995, 'Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors', Biochemical Pharmacology, vol. 50, no. 1, pp. 83-90. https://doi.org/10.1016/0006-2952(95)00109-D

TY - JOUR

T1 - Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors

AU - Mechoulam, Raphael

AU - Ben-Shabat, Shimon

AU - Hanus, Lumir

AU - Ligumsky, Moshe

AU - Kaminski, Norbert E.

AU - Schatz, Anthony R.

AU - Gopher, Asher

AU - Almog, Shlomo

AU - Martin, Billy R.

AU - Compton, David R.

AU - Pertwee, Roger G.

AU - Griffin, Graeme

AU - Bayewitch, Michael

AU - Barg, Jacob

AU - Vogel, Zvi

PY - 1995/6/29

Y1 - 1995/6/29

N2 - 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.

AB - 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.

KW - 2-arachidonyl glycerol

KW - adenylate cyclase inhibition

KW - anandamide

KW - arachidonylethanolamide

KW - immune system

KW - mouse behavior

KW - tetrahydrocannabinol

KW - transfection

UR - https://www.scopus.com/pages/publications/0029012014

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DO - 10.1016/0006-2952(95)00109-D

M3 - Article

AN - SCOPUS:0029012014

SN - 0006-2952

VL - 50

SP - 83

EP - 90

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

IS - 1

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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