Jm. Peltonen et al., SUBTYPE-SPECIFIC STIMULATION OF [S-35] GTP-GAMMA-S BINDING BY RECOMBINANT ALPHA(2)-ADRENOCEPTORS, European journal of pharmacology, 355(2-3), 1998, pp. 275-279
We measured agonist-stimulated binding of the stable GTP-analog guanos
ine-5'-O-(3-[S-35]thiotriphosphate) ([S-35]GTP gamma S) as a functiona
l assay to monitor G-protein activation by recombinant human alpha(2)-
adrenoceptor subtypes alpha(2A), alpha(2B), and alpha(2C). (-)-Noradre
naline was a full agonist in all receptors. Dexmedetomidine, UK14,304,
clonidine and oxymetazoline showed subtype-selectivity in efficacy. D
exmedetomidine was a full agonist at a,, and a partial agonist at alph
a(2A); UK14,304 was a full agonist at alpha(2A) and a partial agonist
at alpha(2B). Clonidine and oxymetazoline were weak partial agonists a
t the alpha(2B)-subtype, but appeared inactive at alpha(2A) and alpha(
2C). The [S-35]GTP gamma S binding assay provides functional informati
on on pertussis toxin-sensitive G-protein activation, complementing ra
dioligand binding assays and conventional second messenger assays. (C)
1998 Elsevier Science B.V. All rights reserved.