The opiate analgesic drugs such as morphine and its congeners
are the most powerful pain-killing agents being prescribed.
However, the overall use of these drugs is hindered by the
possibility of tolerance and dependence or addiction development
in patients. Thus, in order to develop a perfect analgesic
agent or pain treatment paradigm, our laboratory actively
pursues the cellular mechanism for tolerance and dependence.
The focus of our research can be classified into three major topics:
(1) the receptor signaling mechanism;
(2) regulation of the receptor activities during chronic treatment; and
(3) the cellular trafficking of the receptor.
Since opioid receptors are members of the rhodopsin subfamily of the super family of G protein-coupled receptors (GPCRs) and their signals are mediated via the Gi/Go heterotrimeric proteins, the receptors are regulated similarly as other members of GPCRs. Our studies on determining the regulation mechanism involve receptor structural analysis, defining the cellular trafficking of the receptor, and identifying the cellular proteins that participate in receptor signaling and regulation. Approaches and techniques use in these studies encompass biochemical, molecular biological, cellular, genetic and proteomic analysis of the components involved. From these studies, an overall mechanism of opioid tolerance and dependence will be developed and tested with in vivo animal models.
Dr. Law is Research Council Chair of the Basic Research Center in Molecular & Cell Biology of Drug Addiction.