Desensitisation of the Adenosine A1 Receptor by the A2A Receptor in the Rat Striatum

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.

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