switch in the intracellular signalling pathway
activated.
In Huntington’s Disease, there are changes in
the expression and function of both CB1 and
A2A in the dorsal striatum. The above study
also showed that the CB1-A2A heteromer is
selectively lost as Huntington’s Disease
progresses to later stages. This may cause
drugs acting on the cannabinoid or adenosine
systems to have different effects early vs. late
in the disease.
CB1 & Orexin Receptors
The orexin OX1 and OX2 receptors bind the
neuropeptides orexin-A and orexin-B. These
receptors regulate many functions which
overlap with cannabinoids, including
wakefulness and sleep, appetite, pain, and
reward.
The CB1 receptor dimerises with both the
OX1 receptor and OX2 receptor. The OX1
receptor activation by an agonist was much
more potent in the presence of the CB1
receptor.
Activation
of
OX1 causes
internalization of the OX1 receptor (this is a
method of downregulating the receptor).
When the CB1 receptor is expressed in the
same cell, CB1 is also internalized through
the heteromer, indicating the two receptors
can be co-regulated. However, we must await
further studies to see how this affects the
biological functions listed above.
CB2 & Chemokine Receptors
Chemokine receptors generate signals that
lead to cellular migration and proliferation.
Although there are important roles for
chemokine receptors in healthy tissues, they
also can promote cancer cell development and
metastasis. Expression of the chemokine
CXCR4 receptor on tumor cells is a negative
prognostic factor associated with increased
tumor aggressiveness, metastasis, and
decreased probability of survival.
A 2016 study has shown that the CB2 and
CXCR4 receptors can form heterodimers in
breast and prostate cancer cells. Simultaneous
activation of both receptors led to reduced
CXCR4 signalling. Downstream effects of
this included reduced cancer cell migration,
which is an important step in metastasis. This
study shows that receptor dimerization is a
new mechanism of how cannabinoids can
exert effects on tumours.