Abstract
IntroductionDopamine (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.MethodsDAR 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.ResultsDAR 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.ConclusionsThis 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.
Highlights
Dopamine (DA) binds to five receptors (DAR), classified by their ability to increase (D1R-like) or decrease (D2Rlike) cAMP
Expression of domain receptors (DAR) in adipose tissue and adipocytes Conventional RT-PCR was used to compare the expression of DAR in sc adipose tissue, striatum and pituitary
Four of the five DAR were detected in adipose tissue, with D1R being the most abundant (Fig. 1A)
Summary
Dopamine (DA) binds to five receptors (DAR), classified by their ability to increase (D1R-like) or decrease (D2Rlike) cAMP. 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. DA binds to five G-proteincoupled, seven transmembrane domain receptors (DAR), classified as those that are linked to stimulation (D1R and D5R) or inhibition (D2R, D3R and D4R) of adenylate cyclase (AC) [1,2]. The D2-like receptors are coupled to Gai/o proteins and inhibit AC, followed by the suppression of cAMP [7]. DA is a pleiotropic compound that acts as a neurotransmitter and a hormone. In peripheral non-neuronal tissues, e.g., pituitary, kidney and blood vessels, DA acts more slowly and affects electrolyte transport, vasodilation, hormone production and cell proliferation [7,8]
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