Receptor Classification

&

Receptor Regulation

陶寶綠 教授
Receptors
 Receptor classification:
Pharmacological Method

R. P. Ahlquist
Am. J. Physiol.
153:586-600, 1948
α

β
Receptor classification:
Receptor Binding Method
Receptor classification:
Cloning Method
The IUPHAR Receptor List
(http://www.iuphar-db.org/iuphar-rd/list/index.htm)
 Receptor Classification
(3) (2)

(1)

(4)
Structural homologies
species varients of receptors: 85-95% homology
inter-family: 15-35% homology
receptor types (36-53% homology for 5-HT receptors)
subtypes (53-80% homology for 5-HT receptors)
 Opioid receptor classification
Cloning of opioid receptors (Evans et al., 1992; Kieffer et al.,
1992; Chen et al., 1993; Meng et al., 1993; Yasuda et al.,
1993)

MOR; µ-opioid receptor (1997)

DOR; δ-opioid receptor
KOR; κ-opioid receptor
 Official IUPHAR
Family IUPHAR Receptor Code Ligand
Nomenclature

Opioid 2.1:OP:2:DELTA: β-Endorphin δ

Opioid 2.1:OP:3:KAPPA: Dynorphin A κ
Opioid 2.1:OP:1:MU: β-Endorphin µ
Opioid 2.1:OP:4:NOCIC: Nociceptin/orphanin FQ
NOP

(2005)
→ OP1
Receptor Regulation

Desensitization
Down-regulation
Up-regulation
Desensitization
 Desensitization
Ex. β-adrenergic receptor
G protein-coupled receptor
kinases (GRK)

There are 7 GRKs known.

Model depicting the desensitization of the β-adrenergic receptor

Thierry Me´taye´a et al., Cellular Signalling 17 (2005) 917–928

Opioid receptors
NMDA receptor regulation by Src kinase signalling
NMDA receptor

glutamate binding site

NR2
NR1 NR1
Mg
glycine binding site
Long term potentiation (LTP)
 Tyrosine phosphorylation upregulates the activity of NMDARs.

Increased phosphorylation at one or more tyrosines on NR2A and

NR2B is responsible for increased channel gating.

CAKβ:
cell-adhesion kinase β

Current Opinion in Neurobiology 2001, 11:336–342

Possible cellular mechanism for long term potentiation (LTP)
Midterm test:

Pick up a receptor and write a report about recent

review(s) regarding to the regulation of this receptor.