Abbreviations used: CCPA, 2-chloro-N6-cyclopentyladenosine; CGS 21680, 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine; DPCPX, 8-cyclopentyl-1,3-dipropylxanthine; HA 1004, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; ZM241385, 4-[2-[7-amino-2-(2-furyl)(1,2,4)-triazin-5-ylamino]-ethyl]phenol.
Abstract: The influence of the adenosine A2A receptor on the A1 receptor was examined in rat striatal nerve terminals, a model for other cells in which these receptors are coexpressed. Incubation of striatal synaptosomes with the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine (CGS 21680) caused the appearance of a low-affinity binding site for the A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA). This effect was blocked by the A2A receptor antagonist ZM241385 and by the protein kinase C inhibitor chelerythrine, but not by the protein kinase A inhibitor N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004). The effect was not seen with striatal membranes or with hypotonically lysed synaptosomes. These results demonstrate a protein kinase C-mediated heterologous desensitisation of the A1 receptor by the A2A receptor.