Combined pretreatment with D 1R and A 1R agonists, but not with either one alone, substantially reduced the D 1R agonist-induced accumulation of cAMP. Pretreatment with the A 1R agonist caused coclustering (coaggregation) of A 1R and D 1R, which was blocked by combined pretreatment with the D 1R and A 1R agonists in both fibroblast cells and in cortical neurons in culture. On the other hand, a low degree of A 1R and D 2R colocalization was observed in cotransfected fibroblasts. A high degree of A 1R and D 1R colocalization, demonstrated in double immunofluorescence experiments with confocal laser microscopy, was found in both cotransfected fibroblast cells and cortical neurons in culture. This selective A 1R/D 1R heteromerization disappeared after pretreatment with the D 1R agonist, but not after combined pretreatment with D 1R and A 1R agonists.
A 1R and D 1R, but not A 1R and D 2R, were found to coimmunoprecipitate in cotransfected fibroblasts. The possible molecular basis for the previously described antagonistic interactions between adenosine A 1 receptors (A 1R) and dopamine D 1 receptors (D 1R) in the brain have been studied in mouse fibroblast Ltk − cells cotransfected with human A 1R and D 1R cDNAs or with human A 1R and dopamine D 2 receptor (long-form) (D 2R) cDNAs and in cortical neurons in culture.
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