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Agonist‐dependent and ‐independent dopamine‐1‐like receptor signalling differentially regulates downstream effectors
Author(s) -
Roosterman Dirk
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13018
Subject(s) - downstream (manufacturing) , agonist , signalling , endogenous agonist , dopamine , microbiology and biotechnology , effector , dopamine receptor , receptor , chemistry , neuroscience , pharmacology , dopamine receptor d1 , biology , biochemistry , business , marketing
De‐regulation of energy metabolism by the dopaminergic system is linked to neurological diseases such as schizophrenia and bipolar disorder. Inverse agonists are thought to be more beneficial in treating neurological diseases than neutral antagonists, but only limited experimental data are available regarding the impact of constitutive signalling on energy metabolism. The aim of the present study was to assess the impact of constitutive dopamine‐1 receptor (D1R) and dopamine‐5 receptor (D5R) signalling on downstream targets in transiently and stably transfected HEK 293T cells. The high constitutive activity of D5R was accompanied by increased Na + /H + exchanger ( NHE ) activity and accelerated glucose degradation due to increased transcription and translation of the Na, K‐ ATP ase‐α3 and NHE ‐2. Chronic treatment with an agonist increased the m RNA levels of the α2 Na,K‐ ATP ase, NHE ‐2 and NHE ‐3. Constitutive D5R activation of a c AMP response element‐based reporter was regulated by G protein‐coupled receptor kinase 2, but this did not affect the cell‐surface abundance of the receptor. Our data suggest that constitutive and agonist‐induced activity of D5R differentially regulates the activity and expression of proteins.