T. Sugiura et al., IS THE CANNABINOID CB1 RECEPTOR A 2-ARACHIDONOYLGLYCEROL RECEPTOR - STRUCTURAL REQUIREMENTS FOR TRIGGERING A CA2-15 CELLS( TRANSIENT IN NG108), Journal of Biochemistry, 122(4), 1997, pp. 890-895
The effects of Delta(9)-tetrahydrocannabinol and 2-arachidonoylglycero
l on the intracellular free Ca2+ concentration ([Ca2+] (i)) in NG108-1
5 cells were examined in detail, We found that Delta(9)-tetrahydrocann
abinol induces a rapid, modest increase in [Ca2+](i). The response was
detectable with 3 nM Delta(9)-tetrahydrocannabinol. We also found tha
t very low concentrations of 2-arachidonoylglycerol elicit a rapid, mo
re prominent increase in [Ca2+](i). Such a response was observed not o
nly in NG108-15 cells but also in N18TG2 cells, The response induced b
y 2-arachidonoylglycerol in either NG108-15 cells or N18TG2 cells was
abolished by pretreatment of the cells with a cannabinoid CB1 receptor
-specific antagonist, SR141716A, suggesting that 2-arachidonoylglycero
l interacts with the CB1 receptor to induce the response, The results
of an experiment involving a phospholipase C inhibitor suggested that
phospholipase C is involved in the rapid increase in [Ca2+](i) induced
by 2-arachidonoylglycerol. We also found that 1(3)-arachidonoylglycer
ol exhibits similar activity to that of 2-arachidonoylglycerol, althou
gh its activity at low concentrations was somewhat weak compared with
that of 2-arachidonoylglycerol. We further confirmed that several stru
ctural analogues of 2-arachidonoylglycerol were less active compared w
ith 2-arachidonoylglycerol. These results suggest that the structure o
f 2-arachidonoylglycerol is strictly recognized by the CB1 receptor, w
hich raises the possibility that the CB1 receptor is originally a 2-ar
achidonoylglycerol receptor.