DESENSITIZATION OF THE ADENOSINE A(1) RECEPTOR BY THE A(2A) RECEPTOR IN THE RAT STRIATUM

The influence of the adenosine A(2A) receptor on the A(1) receptor was examined in rat striatal nerve terminals, a model for other cells in which these receptors are coexpressed. Incubation of striatal synaptos omes with the A(2A) receptor agonist hyl)phenethyl-amino-5'-N-ethylcar boxamidoadenosine (CGS 21680) caused the appearance of a low-affinity binding site for the A(1) receptor agonist 2-chloro-N-6-cyclopentylade nosine (CCPA). This effect was blocked by the A(2A) receptor antagonis t ZM241385 and by the protein kinase C inhibitor chelerythrine, but no t by the protein kinase A inhibitor N-(2-guanidinoethyl)-5-isoquinolin esulfonamide (HA 1004). The effect was not seen with striatal membrane s or with hypotonically lysed synaptosomes. These results demonstrate a protein kinase C-mediated heterologous desensitisation of the A(1) r eceptor by the A(2A) receptor.