Dopamine responsiveness is regulated by targeted sorting of D2 receptors

S E Bartlett, Johan Enquist, F W Hopf, J H Lee, F Gladher, V Kharazia, M Waldhoer, W S Mailliard, R Armstrong, A Bonci, J L Whistler

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

130 Citeringar (SciVal)

Sammanfattning

Aberrant dopaminergic signaling is a critical determinant in multiple psychiatric disorders, and in many disease states, dopamine receptor number is altered. Here we identify a molecular mechanism that selectively targets D2 receptors for degradation after their activation by dopamine. The degradative fate of D2 receptors is determined by an interaction with G protein coupled receptor-associated sorting protein (GASP). As a consequence of this GASP interaction, D2 responses in rat brain fail to resensitize after agonist treatment. Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors.
Originalspråkengelska
Sidor (från-till)11521-11526
TidskriftProceedings of the National Academy of Sciences
Volym102
Utgåva32
DOI
StatusPublished - 2005

Ämnesklassifikation (UKÄ)

  • Farmakologi och toxikologi

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