Inhibitory effect of the D3 dopamine receptor on insulin receptor expression and function in vascular smooth muscle cells

Abstract

Background Vascular smooth muscle cell (VSMC) proliferation is regulated by numerous hormones and humoral factors. Our previous study found that stimulation of D1-like dopamine receptors inhibited insulin receptor expression and function in VSMCs. We hypothesize that there is also an interaction between D3 dopamine and insulin receptors, i.e., stimulation of the D3 receptor inhibits insulin receptor expression and function. Methods Receptor expression was determined by immunoblotting, immunohistochemisty, and reverse transcriptase-PCR; VSMC proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-diphenyl-tetrazolium bromide (MTT) assay and cell number. Results Insulin receptor protein is increased in the aorta of D3 receptor deficient mice. Stimulation of the D3 receptor inhibited insulin receptor mRNA and protein expression and insulin-mediated VSMC proliferation, and increased protein kinase A (PKA) activity, insulin receptor phosphorylation, and degradation in immortalized aortic VSMCs (A10 cells). These effects were blocked by a PKA inhibitor, indicating that the D3 receptor-mediated decrease in insulin receptor expression was related to a decrease in transcription/post-transcription and increased degradation, involving PKA signaling. Conclusions D3 receptor stimulation may be a target to reduce the adverse effect of insulin in hypertension by inhibition of insulin receptor expression and function in arterial VSMCs. © 2011 American Journal of Hypertension, Ltd.