BML-190 and AM251 act as inverse agonists at the human cannabinoid CB2 receptor: Signalling via cAMP and inositol phosphates

David C. New; Yung H. Wong

doi:10.1016/S0014-5793(03)00048-6

BML-190 and AM251 act as inverse agonists at the human cannabinoid CB₂ receptor: Signalling via cAMP and inositol phosphates

David C. New, Yung H. Wong^*

^*Corresponding author for this work

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31 Citations (Scopus)

Abstract

The aminoalkylindole BML-190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB₂ and CB₁ receptors, respectively. In HEK-293 cells stably expressing the human CB₂ receptor, BML-190 and AM251 potentiated the forskolin-stimulated accumulation of cAMP. Moreover, the CB₂ receptor can interact productively with 16z44, a promiscuous Gα_16/z chimera. BML-190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB₂ receptor and 16z44. These results demonstrate that BML-190 and AM251 act as inverse agonists at the human CB₂ receptor acting via Gα_i/o and Gα_q family-coupled pathways.

Original language	English
Pages (from-to)	157-160
Number of pages	4
Journal	FEBS Letters
Volume	536
Issue number	1-3
DOIs	https://doi.org/10.1016/S0014-5793(03)00048-6
Publication status	Published - 11 Feb 2003

Keywords

AM251
BML-190
CB
Cannabinoid
Inverse agonist

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10.1016/S0014-5793(03)00048-6

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title = "BML-190 and AM251 act as inverse agonists at the human cannabinoid CB2 receptor: Signalling via cAMP and inositol phosphates",

abstract = "The aminoalkylindole BML-190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB2 and CB1 receptors, respectively. In HEK-293 cells stably expressing the human CB2 receptor, BML-190 and AM251 potentiated the forskolin-stimulated accumulation of cAMP. Moreover, the CB2 receptor can interact productively with 16z44, a promiscuous Gα16/z chimera. BML-190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB2 receptor and 16z44. These results demonstrate that BML-190 and AM251 act as inverse agonists at the human CB2 receptor acting via Gαi/o and Gαq family-coupled pathways.",

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T2 - Signalling via cAMP and inositol phosphates

AU - New, David C.

AU - Wong, Yung H.

PY - 2003/2/11

Y1 - 2003/2/11

N2 - The aminoalkylindole BML-190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB2 and CB1 receptors, respectively. In HEK-293 cells stably expressing the human CB2 receptor, BML-190 and AM251 potentiated the forskolin-stimulated accumulation of cAMP. Moreover, the CB2 receptor can interact productively with 16z44, a promiscuous Gα16/z chimera. BML-190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB2 receptor and 16z44. These results demonstrate that BML-190 and AM251 act as inverse agonists at the human CB2 receptor acting via Gαi/o and Gαq family-coupled pathways.

AB - The aminoalkylindole BML-190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB2 and CB1 receptors, respectively. In HEK-293 cells stably expressing the human CB2 receptor, BML-190 and AM251 potentiated the forskolin-stimulated accumulation of cAMP. Moreover, the CB2 receptor can interact productively with 16z44, a promiscuous Gα16/z chimera. BML-190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB2 receptor and 16z44. These results demonstrate that BML-190 and AM251 act as inverse agonists at the human CB2 receptor acting via Gαi/o and Gαq family-coupled pathways.

KW - AM251

KW - BML-190

KW - CB

KW - Cannabinoid

KW - Inverse agonist

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UR - https://www.scopus.com/pages/publications/0037432136

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DO - 10.1016/S0014-5793(03)00048-6

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JO - FEBS Letters

JF - FEBS Letters

IS - 1-3

ER -

BML-190 and AM251 act as inverse agonists at the human cannabinoid CB₂ receptor: Signalling via cAMP and inositol phosphates

Abstract

Keywords

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