Dopamine receptors in human adipocytes: expression and functions.

<h4>Introduction</h4>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...

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Autores principales: Dana C Borcherding, Eric R Hugo, Gila Idelman, Anuradha De Silva, Nathan W Richtand, Jean Loftus, Nira Ben-Jonathan
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:f5dba42807724d7fa478d4bcba5905952021-11-04T06:07:46ZDopamine receptors in human adipocytes: expression and functions.1932-620310.1371/journal.pone.0025537https://doaj.org/article/f5dba42807724d7fa478d4bcba5905952011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21966540/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Dana C BorcherdingEric R HugoGila IdelmanAnuradha De SilvaNathan W RichtandJean LoftusNira Ben-JonathanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e25537 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Dana C Borcherding
Eric R Hugo
Gila Idelman
Anuradha De Silva
Nathan W Richtand
Jean Loftus
Nira Ben-Jonathan
Dopamine receptors in human adipocytes: expression and functions.
description <h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
format article
author Dana C Borcherding
Eric R Hugo
Gila Idelman
Anuradha De Silva
Nathan W Richtand
Jean Loftus
Nira Ben-Jonathan
author_facet Dana C Borcherding
Eric R Hugo
Gila Idelman
Anuradha De Silva
Nathan W Richtand
Jean Loftus
Nira Ben-Jonathan
author_sort Dana C Borcherding
title Dopamine receptors in human adipocytes: expression and functions.
title_short Dopamine receptors in human adipocytes: expression and functions.
title_full Dopamine receptors in human adipocytes: expression and functions.
title_fullStr Dopamine receptors in human adipocytes: expression and functions.
title_full_unstemmed Dopamine receptors in human adipocytes: expression and functions.
title_sort dopamine receptors in human adipocytes: expression and functions.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/f5dba42807724d7fa478d4bcba590595
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AT anuradhadesilva dopaminereceptorsinhumanadipocytesexpressionandfunctions
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AT jeanloftus dopaminereceptorsinhumanadipocytesexpressionandfunctions
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