IDENTIFICATION OF AN ENDOGENOUS 2-MONOGLYCERIDE, PRESENT IN CANINE GUT, THAT BINDS TO CANNABINOID RECEPTORS

R  MECHOULAM; S  BENSHABAT; L  HANUS; M  LIGUMSKY; N E  KAMINSKI; A R  SCHATZ; A  GOPHER; S  ALMOG; D R  COMPTON; Roger Guy Pertwee; G  GRIFFIN; M  BAYEWITCH; J  BARG; Z  VOGEL; Billy R. Martin

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

IDENTIFICATION OF AN ENDOGENOUS 2-MONOGLYCERIDE, PRESENT IN CANINE GUT, THAT BINDS TO CANNABINOID RECEPTORS

R MECHOULAM, S BENSHABAT, L HANUS, M LIGUMSKY, N E KAMINSKI, A R SCHATZ, A GOPHER, S ALMOG, D R COMPTON, Roger Guy Pertwee, G GRIFFIN, M BAYEWITCH, J BARG, Z VOGEL, Billy R. Martin

Medical Sciences

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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 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.

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
Publication status	Published - 29 Jun 1995

Keywords

2-ARACHIDONYL GLYCEROL
ANAND AMIDE
TETRAHYDROCANNABINOL
ARACHIDONYLETHANOLAMIDE
IMMUNE SYSTEM
TRANSFECTION
MOUSE BEHAVIOR
ADENYLATE CYCLASE INHIBITION
MOUSE SPLEEN-CELLS
CANNABIMIMETIC AGENTS
BRAIN CONSTITUENT
ADENYLATE-CYCLASE
ANANDAMIDE
DELTA-9-TETRAHYDROCANNABINOL
EXPRESSION
INHIBITION
AGONIST
2-arachidonyl glycerol
tetrahydrocannabinol
anandamide
arachidonylethanolamide
immune system
transfection
mouse behavior
adenylate cyclase inhibition

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10.1016/0006-2952(95)00109-D

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MECHOULAM, R., BENSHABAT, S., HANUS, L., LIGUMSKY, M., KAMINSKI, N. E., SCHATZ, A. R., GOPHER, A., ALMOG, S., COMPTON, D. R., Pertwee, R. G., GRIFFIN, G., BAYEWITCH, M., BARG, J., VOGEL, Z., & Martin, B. R. (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

MECHOULAM, R, BENSHABAT, S, HANUS, L, LIGUMSKY, M, KAMINSKI, NE, SCHATZ, AR, GOPHER, A, ALMOG, S, COMPTON, DR, Pertwee, RG, GRIFFIN, G, BAYEWITCH, M, BARG, J, VOGEL, Z & Martin, BR 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

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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 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 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.",

keywords = "2-ARACHIDONYL GLYCEROL, ANAND AMIDE, TETRAHYDROCANNABINOL, ARACHIDONYLETHANOLAMIDE, IMMUNE SYSTEM, TRANSFECTION, MOUSE BEHAVIOR, ADENYLATE CYCLASE INHIBITION, MOUSE SPLEEN-CELLS, CANNABIMIMETIC AGENTS, BRAIN CONSTITUENT, ADENYLATE-CYCLASE, ANANDAMIDE, DELTA-9-TETRAHYDROCANNABINOL, EXPRESSION, INHIBITION, AGONIST, 2-arachidonyl glycerol, tetrahydrocannabinol, anandamide, arachidonylethanolamide, immune system, transfection, mouse behavior, adenylate cyclase inhibition",

author = "R MECHOULAM and S BENSHABAT and L HANUS and M LIGUMSKY and KAMINSKI, {N E} and SCHATZ, {A R} and A GOPHER and S ALMOG and COMPTON, {D R} and Pertwee, {Roger Guy} and G GRIFFIN and M BAYEWITCH and J BARG and Z VOGEL and Martin, {Billy R.}",

year = "1995",

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day = "29",

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

language = "English",

volume = "50",

pages = "83--90",

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T1 - IDENTIFICATION OF AN ENDOGENOUS 2-MONOGLYCERIDE, PRESENT IN CANINE GUT, THAT BINDS TO CANNABINOID RECEPTORS

AU - MECHOULAM, R

AU - BENSHABAT, S

AU - HANUS, L

AU - LIGUMSKY, M

AU - KAMINSKI, N E

AU - SCHATZ, A R

AU - GOPHER, A

AU - ALMOG, S

AU - COMPTON, D R

AU - Pertwee, Roger Guy

AU - GRIFFIN, G

AU - BAYEWITCH, M

AU - BARG, J

AU - VOGEL, Z

AU - Martin, Billy R.

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 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 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.

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 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 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.

KW - 2-ARACHIDONYL GLYCEROL

KW - ANAND AMIDE

KW - TETRAHYDROCANNABINOL

KW - ARACHIDONYLETHANOLAMIDE

KW - IMMUNE SYSTEM

KW - TRANSFECTION

KW - MOUSE BEHAVIOR

KW - ADENYLATE CYCLASE INHIBITION

KW - MOUSE SPLEEN-CELLS

KW - CANNABIMIMETIC AGENTS

KW - BRAIN CONSTITUENT

KW - ADENYLATE-CYCLASE

KW - ANANDAMIDE

KW - DELTA-9-TETRAHYDROCANNABINOL

KW - EXPRESSION

KW - INHIBITION

KW - AGONIST

KW - 2-arachidonyl glycerol

KW - tetrahydrocannabinol

KW - anandamide

KW - arachidonylethanolamide

KW - immune system

KW - transfection

KW - mouse behavior

KW - adenylate cyclase inhibition

U2 - 10.1016/0006-2952(95)00109-D

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

M3 - Article

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

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