M. Egertova et Mr. Elphick, Localisation of cannabinoid receptors in the rat brain using antibodies tothe intracellular C-terminal tail of CB1, J COMP NEUR, 422(2), 2000, pp. 159-171
The CB1-type cannabinoid receptor mediates physiologic effects of Delta(9)-
tetrahydrocannabinol, the psychoactive ingredient of the drug marijuana. In
this report, the authors analyse the expression of CB1 in the rat brain by
using antibodies to the C-terminal 13 amino acids of the receptor. Western
blot analysis of rat brain membranes revealed a prominent immunoreactive b
and with a molecular mass (approximate to 53 kDa) consistent with that pred
icted for CB1 from the rat cDNA sequence. In addition, however, less intens
e immunoreactive bands corresponding to glycosylated ( approximate to 62 kD
a) and putative N-terminally shorter (approximate to 45 kDa) isoforms of CB
1 were detected. The distribution of CB1-immunoreactivity in rat brain was
similar to the distribution of binding sites for radiolabelled cannabinoids
, with high levels of expression in the olfactory system, the hippocampal f
ormation, the basal ganglia, the cerebellum, and the neocortex. This provid
es important evidence that CB1 is likely to be largely responsible for medi
ating effects of cannabinoids in the brain. CB1 immunoreactivity was associ
ated with nerve fibre systems and axon terminals but was not detected in ne
uronal somata. This is consistent with the presynaptic inhibitory effects o
f cannabinoids on neurotransmitter release in the brain. Detailed immunocyt
ochemical analysis of anatomically or functionally related regions of the b
rain revealed the location of CB1 receptors within identified neural circui
ts. Determination of the cellular and subcellular location of CB1 within kn
own neuronal circuits of the brain provides an anatomic framework for inter
pretation of the neurophysiologic and behavioural effects of cannabinoids.
(C) 2000 Wiley-Liss, Inc.