Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel

Nature ◽  
1993 ◽  
Vol 364 (6440) ◽  
pp. 802-806 ◽  
Author(s):  
Yoshihiro Kubo ◽  
Eitan Reuveny ◽  
Paul A. Slesinger ◽  
Yuh Nung Jan ◽  
Lily Y. Jan
1995 ◽  
Vol 15 (2) ◽  
pp. 106-113
Author(s):  
Yoshihiro Kubo ◽  
Eitan Reuveny ◽  
Paul A Slesinger ◽  
Timothy J Baldwin ◽  
Yuh Nung Jan ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 484
Author(s):  
Dongchen An ◽  
Steve Peigneur ◽  
Jan Tytgat

The coupling of cannabinoid receptors, CB1 and CB2, to G protein-coupled inward rectifier potassium channels, GIRK1 and GIRK2, modulates neuronal excitability in the human brain. The present study established and validated the functional expression in a Xenopus laevis oocyte expression system of CB1 and CB2 receptors, interacting with heteromeric GIRK1/2 channels and a regulator of G protein signaling, RGS4. This ex vivo system enables the discovery of a wide range of ligands interacting orthosterically or allosterically with CB1 and/or CB2 receptors. WIN55,212-2, a non-selective agonist of CB1 and CB2, was used to explore the CB1- or CB2-GIRK1/2-RGS4 signaling cascade. We show that WIN55,212-2 activates CB1 and CB2 at low concentrations whereas at higher concentrations it exerts a direct block of GIRK1/2. This illustrates a dual modulatory function, a feature not described before, which helps to explain the adverse effects induced by WIN55,212-2 in vivo. When comparing the effects with other typical cannabinoids such as Δ9-THC, CBD, CP55,940, and rimonabant, only WIN55,212-2 can significantly block GIRK1/2. Interestingly, the inward rectifier potassium channel, IRK1, a non-G protein-coupled potassium channel important for setting the resting membrane voltage and highly similar to GIRK1 and GIRK2, is not sensitive to WIN55,212-2, Δ9-THC, CBD, CP55,940, or rimonabant. From this, it is concluded that WIN55,212-2 selectively blocks GIRK1/2.


Author(s):  
Martha J. Larsen ◽  
Elizabeth Ruiz Lancheros ◽  
Tracey Williams ◽  
David E. Lowery ◽  
Timothy G. Geary ◽  
...  

1995 ◽  
Vol 92 (25) ◽  
pp. 11711-11715 ◽  
Author(s):  
X. Yao ◽  
A. S. Segal ◽  
P. Welling ◽  
X. Zhang ◽  
C. M. McNicholas ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document