title: Dopamine receptors in human adipocytes: expression and functions.
abstract: BACKGROUND
  Dopamine (DA) binds to five receptors (DAR), classified by their ability to increase (D1R-like) or decrease (D2R-like) cAMP. In humans, most DA circulates as dopamine sulfate (DA-S), which can be de-conjugated to bioactive DA by arylsulfatase A (ARSA). The objective was to examine expression of DAR and ARSA in human adipose tissue and determine whether DA regulates prolactin (PRL) and adipokine expression and release.
  
  
  METHODS
  DAR were analyzed by RT-PCR and Western blotting in explants, primary adipocytes and two human adipocyte cell lines, LS14 and SW872. ARSA expression and activity were determined by qPCR and enzymatic assay. PRL expression and release were determined by luciferase reporter and Nb2 bioassay. Analysis of cAMP, cGMP, leptin, adiponectin and interleukin 6 (IL-6) was done by ELISA. Activation of MAPK and PI3 kinase/Akt was determined by Western blotting.
  
  
  RESULTS
  DAR are variably expressed at the mRNA and protein levels in adipose tissue and adipocytes during adipogenesis. ARSA activity in adipocyte increases after differentiation. DA at nM concentrations suppresses cAMP, stimulates cGMP, and activates MAPK in adipocytes. Acting via D2R-like receptors, DA and DA-S inhibit PRL gene expression and release. Acting via D1R/D5R receptors, DA suppresses leptin and stimulates adiponectin and IL-6 release.
  
  
  CONCLUSIONS
  This is the first report that human adipocytes express functional DAR and ARSA, suggesting a regulatory role for peripheral DA in adipose functions. We speculate that the propensity of some DAR-activating antipsychotics to increase weight and alter metabolic homeostasis is due, in part, to their direct action on adipose tissue.
authors.affiliation: Department of Cancer and Cell Biology, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Borcherding
authors.forename: Eric R
authors.initials: ER
authors.lastname: Hugo
authors.forename: Gila
authors.initials: G
authors.lastname: Idelman
authors.forename: Anuradha
authors.initials: A
authors.lastname: De Silva
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Richtand
authors.forename: Jean
authors.initials: J
authors.lastname: Loftus
authors.forename: Nira
authors.initials: N
authors.lastname: Ben-Jonathan
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism*
chemical_list: D011954:Receptors, Dopamine; D000242:Cyclic AMP; D002553:Cerebroside-Sulfatase; D006152:Cyclic GMP