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My name is Ying-Xian Pan, I'm a member
of the Department of Neurology at
the Memorial Sloan-Kettering
Cancer Center.
My research interests have
long focused on GPCRs,
particularly the mu opioid receptors.
Today, I will talk about biased signaling
at the mu opioid receptor splice variants.
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Earlier pharmacological studies defined
three types of opiate receptors,
mu, kappa and delta.
Molecular cloning led to
identification of their
corresponding genes OPRM1,
OPRK1, and OPRD1,
and their receptor proteins MOR-1 (MOP),
KOR-1 (KOP) and DOR-1 (DOP).
There is a fourth member of
the opioid receptor gene family,
OPRN1, encoding ORL-1 or NOP.
Structurally, NOP shares high
homology with the other three
opioid receptors, but
does not bind to any opiate.
The crystal structures of all
four receptors were resolved and
published in the same
issue of Nature in 2012.
The mu opioid receptor has a special
place in the opioid receptor family,
because it mediates the actions of
most of the clinically-used opioids
such as morphine, fentanyl and
methadone, as well as heroin.
Mu opioid agonists can
effectively relieve pain,
mainly severe pain such
as that caused by cancer.
However, they also cause many
side-effects including tolerance,
physical dependence, respiratory
depression, addiction and so on.
Our goal is to understand the molecular
mechanisms of opioid actions,
and we hope to develop better analgesic
drugs with limited side-effects.
