G-protein Effects on 3HRX821002 Binding to Alpha-2 Adrenoceptor in Rat Brain.
- Author:
In Won CHUNG
1
;
Ji Yong SHIN
;
Chul Jin SHIN
Author Information
1. Department of Neuropsychiatry, College of Medicine, Chungbuk National University, Cheongju, Korea. iwchung@med.chungbuk.ac.kr
- Publication Type:Original Article
- Keywords:
Alpha-2 adrenergic receptor;
[3H]RX821002;
G-protein;
Gpp(NH)p;
Pertussis toxin
- MeSH:
Animals;
Binding Sites;
Brain*;
GTP-Binding Proteins*;
Guanylyl Imidodiphosphate;
Pertussis Toxin;
Rats*;
Receptors, Adrenergic, alpha-2
- From:Korean Journal of Psychopharmacology
2001;12(4):301-309
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVE: This study is to explore the effects on specific bindings between [ 3H]RX821002, alpha-2 adrenergic receptor antagonist and alpha-2 adrenergic receptor in rat brain by G-protein modulation. METHODS: The radioligand binding receptor study was conducted with [ 3H]RX821002, a new alpha-2 adrenergic receptor antagonist, in the presence or absence of Gpp(NH)p and pertussis toxin. RESULTS: The alpha-2 adrenergic receptors were saturated with [ 3H]RX821002 in the fashion of the single binding site. The dissociation constant (Kd) was 0.70+/-0.30 nM, and maximum binding (Bmax) was 599.9+/-283.4 fmol/mg protein. The saturation study showed that the maximum binding (B max ; 668.0+/-50.1 fmol/mg protein) was increased and the dissociation constant (Kd ; 0.61+/-0.14 nM) was decreased significantly in the presence of Gpp (NH)p compared to those (B max ; 559.8+/-81.9 fmol/mg protein, Kd ; 0.87+/-0.14 nM) in the absence of Gpp (NH)p (by paired t-test ; B max, p=0.023, Kd, p=0.005). In the presence of pertussis toxin, the maximum binding (B max ; 617.0+/-58.5 fmol/mg protein) was increased significantly (by paired t-test ; B max, p=0.001) but the issociation constant (Kd ; 0.92+/-0.24 nM) was not decreased compared to those (B max ; 554.1+/-66.1 fmol/mg protein, Kd ; 0.89+/-0.24 nM) in the absence of pertussis toxin. CONCLUSION: These results confirm that the binding profiles between [ 3H]RX821002 and alpha-2 adrenergic receptors be modified by G-protein modulation. This suggests that the drug effects on receptors be influenced by various conditions such as G-protein modulation.
