Endocannabinoid Receptors – More Than Just CB1 and CB2 (Part 2)
Receptor Dimerisation - Expanding the reach of Cannabinoids
Cannabinoid receptors can link with other
receptors and modify their function, opening
a new avenue for understanding how
cannabinoid exert their effects.
I previously showed how endocannabinoids
like anandamide can directly interact with
receptors outside the cannabinoid system.
However, this alone does not explain the
multitude of effects that cannabinoids have.
There is another important way that
cannabinoids can interact with other systems
– this is through receptor dimerisation.
This process is turning out to be so important
for how cannabinoids work – including both
for beneficial health effects as well as for
undesired side effects. For example, a
potential role of cannabinoid receptor dimers
has been explored in:
• Tolerance to pain-blocking effects of
opiates
• Depression and anxiety in chronic pain
• Negative effects of cannabis on
memory
• Parkinson’s and Huntington’s Disease
• Cancer cell metastasis
GPCR Dimerisation
CB1 and CB2 belong to a class of receptors
called G-protein coupled receptors (or
GPCRs). These receptors were traditionally
thought to function as independent units.
Then it was discovered that two of the same
GPCRs could come together in the cell
membrane to form a receptor homodimer.
The CB1 receptor homodimer was first
characterised in a 2002 study, although the
consequences of this remain unknown
The next discovery was even more surprising
– different types of GPCRs could bind each
other to form a receptor heterodimer (also
called a heteromer for short). This opened up
an exponential number of ways that a single
receptor (for example, the cannabinoid CB1
receptor) could influence other
neurotransmitter systems.
What can heterodimerization change about
how the receptor functions? A lot of things:
• Receptor signalling: Increasing or
decreasing the signal generated from
the receptor or even changing the
signalling pathway activated by the
receptor.
• Ligand binding: Changing the affinity
of a ligand for its receptor
• Receptor Trafficking: Location of the
receptor
on
the
membrane
or internalisation of the receptor into
the cell
I will highlight the effects of some key
cannabinoid receptor dimers below: