Abstract
We examined the effect of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, on the intracellular free Ca2+ concentrations in HL-60 cells that express the cannabinoid CB2 receptor. We found that 2- arachidonoylglycerol induces a rapid transient increase in intracellular free Ca2+ concentrations in HL-60 cells. The response was affected by neither cyclooxygenase inhibitors nor lipoxygenase inhibitors, suggesting that arachidonic acid metabolites are not involved. Consistent with this notion, free arachidonic acid was devoid of any agonistic activity. Importantly, the Ca2+ transient induced by 2-arachidonoylglycerol was blocked by pretreatment of the cells with SR144528, a CB2 receptor-specific antagonist, but not with SR141716A, a CB1 receptor-specific antagonist, indicating the involvement of the CB2 receptor but not the CB1 receptor in this cellular response. G(i) or G(o) is also assumed to be involved, because pertussis toxin treatment of the cells abolished the response. We further examined the structure-activity relationship. We found that 2-arachidonoylglycerol is the most potent compound among a number of naturally occurring cannabimimetic molecules. Interestingly, anandamide and N-palmitoylethanolamine, other putative endogenous ligands, were found to be a weak partial agonist and an inactive ligand, respectively. These results strongly suggest that the CB2 receptor is originally a 2-arachidonoylglycerol receptor, and 2- arachidonoylglycerol is the intrinsic natural ligand for the CB2 receptor that is abundant in the immune system.
| Original language | English |
|---|---|
| Pages (from-to) | 605-612 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 275 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2000 Jan 7 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Biochemistry
Cite this
Evidence that 2-arachidonoylglycerol but not N-palmitoylethanolamine or anandamide is the physiological ligand for the cannabinoid CB2 receptor. Comparison of the agonistic activities of various cannabinoid receptor ligands in HL-60 cells. / Sugiura, Takayuki; Kondo, Sachiko; Kishimoto, Seishi; Miyashita, Tomoyuki; Nakane, Shinji; Kodaka, Tomoko; Suhara, Yoshitomo; Takayama, Hiroaki; Waku, Keizo.
In: Journal of Biological Chemistry, Vol. 275, No. 1, 07.01.2000, p. 605-612.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evidence that 2-arachidonoylglycerol but not N-palmitoylethanolamine or anandamide is the physiological ligand for the cannabinoid CB2 receptor. Comparison of the agonistic activities of various cannabinoid receptor ligands in HL-60 cells
AU - Sugiura, Takayuki
AU - Kondo, Sachiko
AU - Kishimoto, Seishi
AU - Miyashita, Tomoyuki
AU - Nakane, Shinji
AU - Kodaka, Tomoko
AU - Suhara, Yoshitomo
AU - Takayama, Hiroaki
AU - Waku, Keizo
PY - 2000/1/7
Y1 - 2000/1/7
N2 - We examined the effect of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, on the intracellular free Ca2+ concentrations in HL-60 cells that express the cannabinoid CB2 receptor. We found that 2- arachidonoylglycerol induces a rapid transient increase in intracellular free Ca2+ concentrations in HL-60 cells. The response was affected by neither cyclooxygenase inhibitors nor lipoxygenase inhibitors, suggesting that arachidonic acid metabolites are not involved. Consistent with this notion, free arachidonic acid was devoid of any agonistic activity. Importantly, the Ca2+ transient induced by 2-arachidonoylglycerol was blocked by pretreatment of the cells with SR144528, a CB2 receptor-specific antagonist, but not with SR141716A, a CB1 receptor-specific antagonist, indicating the involvement of the CB2 receptor but not the CB1 receptor in this cellular response. G(i) or G(o) is also assumed to be involved, because pertussis toxin treatment of the cells abolished the response. We further examined the structure-activity relationship. We found that 2-arachidonoylglycerol is the most potent compound among a number of naturally occurring cannabimimetic molecules. Interestingly, anandamide and N-palmitoylethanolamine, other putative endogenous ligands, were found to be a weak partial agonist and an inactive ligand, respectively. These results strongly suggest that the CB2 receptor is originally a 2-arachidonoylglycerol receptor, and 2- arachidonoylglycerol is the intrinsic natural ligand for the CB2 receptor that is abundant in the immune system.
AB - We examined the effect of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, on the intracellular free Ca2+ concentrations in HL-60 cells that express the cannabinoid CB2 receptor. We found that 2- arachidonoylglycerol induces a rapid transient increase in intracellular free Ca2+ concentrations in HL-60 cells. The response was affected by neither cyclooxygenase inhibitors nor lipoxygenase inhibitors, suggesting that arachidonic acid metabolites are not involved. Consistent with this notion, free arachidonic acid was devoid of any agonistic activity. Importantly, the Ca2+ transient induced by 2-arachidonoylglycerol was blocked by pretreatment of the cells with SR144528, a CB2 receptor-specific antagonist, but not with SR141716A, a CB1 receptor-specific antagonist, indicating the involvement of the CB2 receptor but not the CB1 receptor in this cellular response. G(i) or G(o) is also assumed to be involved, because pertussis toxin treatment of the cells abolished the response. We further examined the structure-activity relationship. We found that 2-arachidonoylglycerol is the most potent compound among a number of naturally occurring cannabimimetic molecules. Interestingly, anandamide and N-palmitoylethanolamine, other putative endogenous ligands, were found to be a weak partial agonist and an inactive ligand, respectively. These results strongly suggest that the CB2 receptor is originally a 2-arachidonoylglycerol receptor, and 2- arachidonoylglycerol is the intrinsic natural ligand for the CB2 receptor that is abundant in the immune system.
UR - http://www.scopus.com/inward/record.url?scp=0034614374&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034614374&partnerID=8YFLogxK
U2 - 10.1074/jbc.275.1.605
DO - 10.1074/jbc.275.1.605
M3 - Article
C2 - 10617657
AN - SCOPUS:0034614374
VL - 275
SP - 605
EP - 612
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 1
ER -