Interactions Between Dopaminergic and Adrenergic Receptors Open Access

Chitrapu, Anjani (2011)

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Interactions Between Dopaminergic and Adrenergic Receptors
By Anjani Chitrapu

Cocaine facilitates dopaminergic and noradrenergic signaling throughout the brain, which are critical for mediating different aspects of cocaine addiction. Both of these neurotransmitters are released in the prefrontal cortex (PFC), a brain region that has been linked to reinstatement of drug-seeking behavior, which models relapse in humans. In particular, the D1-dopamine receptor (D1DR) and α1-adrenergic receptor (α1AR) have been implicated in relapse-like behavior. Pharmacological and biochemical interactions between these receptors have been reported in the PFC, although the exact nature of these interactions is not clear. Additionally, the α1bAR subtype of AR has been linked to neurochemical and behavioral responses to cocaine. Previous research in our lab has shown that D1DR and α1bAR co-localize to dendrites in the PFC, suggesting that the interactions occur cell-autonomously. We hypothesized that D1DR and α1bAR physically interact by forming heterodimers. Using co-immunoprecipitation studies in transfected HEK293 cells, it was confirmed that D1DR and α1bAR are capable of forming stable complexes. We also found evidence for heterodimer formation between other AR and DR subtypes. Given the physical interaction between D1DR and α1bAR, we tested whether agonistinduced internalization of one receptor would alter trafficking of the other receptor. Using a surface luminescence assay, we found that treatment with the α1AR agonist phenylephrine induced ~ 30% internalization of the α1bAR when expressed alone or in combination with D1DR. By contrast, DR stimulation with dopamine increased surface expression of α1bAR only in cells co-expressing both receptors. These results suggest that dopaminergic and adrenergic receptors are capable of forming a complex, and that the trafficking of these receptors may be altered in the heterodimer form.

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