Regulator of G protein signaling proteins differentially modulate signaling of mu and delta opioid receptors.
Effects of regulator of G protein signaling (RGS) proteins on mu and delta opioid receptors were investigated in HEK293 cells. Co-expression of RGS1, RGS2, RGS4, RGS9, RGS10 or RGS19 (Galpha-interacting protein (GAIP)) significantly reduced [Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol]-Enkephalin (DAMGO)-induced inhibition of adenylyl cyclase (AC) mediated by mu opioid receptor, but only RGS9 decreased the effects of [Tyr-D-Pen-Gly-p-Chloro-Phe-D-Pen]-Enkephalin (DPDPE) mediated by delta opioid receptor. When C-tails of the receptors were exchanged (mu/deltaC and delta/muC chimeras), RGS proteins decreased delta/muC-mediated AC inhibition, but none had significant effects on that via mu/deltaC receptor. Thus, the C-terminal domains of the receptors are critical for the differential effects of RGS proteins, which may be due to differences in receptor-G protein-RGS protein interactions in signaling complexes.
Xie
Zhihua
Z
Department of Pharmacology, School of Basic Medicine and Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing 100005, China.
Li
Zhisong
Z
Guo
Lei
L
Ye
Caiying
C
Li
Juan
J
Yu
Xiaoli
X
Yang
Huifen
H
Wang
Yulin
Y
Chen
Chongguang
C
Zhang
Dechang
D
Liu-Chen
Lee-Yuan
LY
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D006801:Humans; D020710:RGS Proteins / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; D020710:RGS Proteins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D005576:Colforsin; D000262:Adenylyl Cyclases