GUANINE NUCLEOSIDE DIPHOSPHATE AND TRIPHOSPHATE MODULATE [H-3] CGS 21680 BINDING TO A2 ADENOSINE RECEPTOR IN RAT STRIATAL MEMBRANES

In striatum and several other tissues, a guanine nucleotide binding protein (G(s)) couples A2 adenosine receptor to activation of adenylyl cyclase. We have examined the effect of guanine nucleoside diphosphate and triphosphate on [H-3]CGS 21680 binding to A2A adenosine receptors of rat striatum. Both GDP and GTP inhibited specific [H-3]CGS 21680 binding to rat striatal membranes by 50% at about 0.1 mM. GMP was inhibitory only at higher concentrations, and the estimated IC50 value was greater than 1 mM. The nonhydrolyzable analog of GTP, Gpp(NH)p, was as potent as GTP with an IC50 value of approximately 86 muM. These results suggest that the regulation of A2a adenosine receptor binding properties by guanine nucleotides is independent of G(s) activation, since inhibition of agonist binding is achieved by addition of both guanine nucleoside diphosphate and triphosphate.