Insulin Increases D5 Dopamine Receptor Expression and Function in Renal Proximal Tubule Cells From Wistar-Kyoto Rats

• Published in: American journal of hypertension 2009-07, Vol.22 (7), p.770-776
• Main Authors: Yang, Jian, Cui, Zhigang, He, Duofen, Ren, Hongmei, Han, Yu, Yu, Changqing, Fu, Chunjiang, Wang, Zheng, Yang, Chengming, Wang, Xukai, Zhou, Lin, Asico, Laureano D., Villar, Van Anthony M., Hopfer, Ulrich, Mi, Mantian, Zeng, Chunyu, Jose, Pedro A.
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cells, Cultured; Experimental diseases; Gene Expression - drug effects; Humans; Insulin - pharmacology; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Medical sciences; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Insulin - metabolism; Receptors, Dopamine D5 - drug effects; Receptors, Dopamine D5 - physiology; Sodium-Potassium-Exchanging ATPase - metabolism; Stimulation, Chemical
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1038/ajh.2009.69

Background Ion transport in the renal proximal tubule (RPT) is regulated by numerous hormones and humoral factors, including insulin and dopamine. Previous studies show an interaction between insulin and the D1 receptor. Because both D1 and D5 receptors belong to the D1-like receptor subfamily, it is possible that an interaction between insulin and the D5 dopamine receptor exists in RPT cells from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Methods D5 receptor expression in immortalized RPT cells from WKY and SHRs was quantified by immunoblotting and D5 receptor function by measuring Na+–K+ ATPase activity. Results Insulin increased the expression of the D5 receptor. Stimulation with insulin (10−7 mol/l) for 24 h increased D5 receptor expression in RPT cells from WKY rats. This effect of insulin on D5 receptor expression was aberrant in RPT cells from SHRs. The stimulatory effect of insulin on D5 receptor expression in RPT cells from WKY rats was inhibited by a protein kinase C (PKC) inhibitor (PKC inhibitor peptide 19–31, 10−6 mol/l) or a phosphatidylinositol 3 (PI3) kinase inhibitor (wortmannin, 10−6 mol/l), indicating that both PKC and PI3 kinase were involved in the signaling pathway. Stimulation of the D5 receptor heterologously expressed in HEK293 cells with fenoldopam (10−7 mol/l/15 min) inhibited Na+–K+ ATPase activity, whereas pretreatment with insulin (10−7 mol/l/24 h) increased the D5 receptor-mediated inhibition. Conclusions Insulin and D5 receptors interact to regulate renal sodium transport; an aberrant interaction between insulin and D5 receptor may participate in the pathogenesis of hypertension.