New Modes of GPCR Signalling

ABSTRACT
The Function of Phosphatidylinositol-Linked Novel D1 Dopamine
Receptor in Central Nervous System
Jian-Guo Chen, Fang Wang, Jue Liu and Li-Qun Ma
Department of Pharamcology and the Key Laboratory of Neurological Disease of
Ministry of Education of China , Tongji Medical College, Huazhong University of
Science and Technology, Wuhan, 430030, China
The physiological actions of dopamine (DA) are mediated via five distinct subtypes
(D1-D5) of G protein-coupled receptors. Stimulation (D1, D5 subtypes) or inhibition
(D2-D4 subtypes) of adenylyl cyclase through Gs/olf or Gi/o proteins by DA receptors
is the traditional signaling pathway. In addition to the Gs/olf-coupled classical D1 DA
receptor that increases the formation of cAMP, a D1-like DA receptor that couples to
Gq protein, stimulates phospholipase Cb (PLCb) and results in hydrolysis of
phosphoinositide has been described and named as PI-linked DA receptor. SKF83959, a
recently identified selective agonist for the PI-linked DA receptor, provided a powerful
tool for exploring the function of this novel signal pathway in brain. However, the
physiological and pathological roles of SKF83959 are unclear. In the recent work from
our laboratory, it has been shown that activation of D1 receptor by SKF83959 mediates
a dose-dependent mobilization of [Ca 2+ ]i via the PLC signaling pathway in cultured rat
prefrontal cortical neurons and astrocytes. It was also inhibited HVA Ca2+ currents in
cultured rat striatal neurons by PLC-IP3-Ca2+-calcineurin signal pathway. Furthermore,
SKF83959 facilitated a postsynaptically PLC-dependent form of LTD at the Schaffer
collater-CA1 synapses. In the pathological condition, SKF83959 mediates more
effective functions of anti-Parkinsonian symptom with less dyskinesia. Our results
provide further understanding for the role of PI-coupled dopamine system that may
mediate important physiological or pathological challenges in the brain.