Inhibition of D4 Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule Cells
BackgroundIon transport in the renal proximal tubule (RPT), which is increased in essential hypertension, is regulated by numerous hormones and humoral factors, including insulin and dopamine. Activation of dopamine receptor inhibits sodium reabsorption, whereas activation of insulin receptor increa...
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| Format: | Article |
| Language: | English |
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Wiley
2016-04-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.115.002448 |
| _version_ | 1819178629156831232 |
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| author | Ye Zhang Hongmei Ren Xi Lu Duofen He Yu Han Hongyong Wang Chunyu Zeng Weibin Shi |
| author_facet | Ye Zhang Hongmei Ren Xi Lu Duofen He Yu Han Hongyong Wang Chunyu Zeng Weibin Shi |
| author_sort | Ye Zhang |
| collection | DOAJ |
| description | BackgroundIon transport in the renal proximal tubule (RPT), which is increased in essential hypertension, is regulated by numerous hormones and humoral factors, including insulin and dopamine. Activation of dopamine receptor inhibits sodium reabsorption, whereas activation of insulin receptor increases sodium reabsorption in RPTs, and hyperinsulinemic animals and patients have defective renal dopaminergic system. We presume that there is an inhibition of D4 receptor on insulin receptor expression and effect, and the regulation is lost in spontaneously hypertensive rats (SHRs). Methods and ResultsInsulin receptor expression was determined by immunoblotting, and Na+‐K+‐ATPase activity was detected in both Wistar‐Kyoto (WKY) and SHR RPT cells. Stimulation of D4 receptor with PD168077 decreased expression of insulin receptors, which was blocked in the presence of the calcium‐channel blocker, nicardipine (10−6 mol/L per 24 hours), in cell culture medium without calcium or in the presence of inositol 1,4,5‐trisphosphate (IP3) receptor blocker (2‐aminoethyl diphenylborinate [2‐ADB]; 10−6 mol/L per 24 hours), indicating that extracellular calcium entry and calcium release from the endoplasmic reticulum were involved in the signal pathway. Stimulation of the insulin receptor stimulated Na+‐K+‐ATPase activity, whereas pretreatment with PD168077 for 24 hours decreased the inhibitory effects of insulin receptor on Na+‐K+‐ATPase activity in WKY cells. However, in SHR cells, inhibition of D4 receptor on insulin receptor expression and effect were lost. ConclusionsActivation of D4 receptor inhibits insulin receptor expression in RPT cells from WKY rats. The aberrant inhibition of D4 receptor on insulin receptor expression and effect might be involved in the pathogenesis of essential hypertension. |
| first_indexed | 2024-12-22T21:45:35Z |
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| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-22T21:45:35Z |
| publishDate | 2016-04-01 |
| publisher | Wiley |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-083d023e605d46cdab384b2bcc9090382022-12-21T18:11:30ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-04-015410.1161/JAHA.115.002448Inhibition of D4 Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule CellsYe Zhang0Hongmei Ren1Xi Lu2Duofen He3Yu Han4Hongyong Wang5Chunyu Zeng6Weibin Shi7Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, ChinaDepartment of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, ChinaBackgroundIon transport in the renal proximal tubule (RPT), which is increased in essential hypertension, is regulated by numerous hormones and humoral factors, including insulin and dopamine. Activation of dopamine receptor inhibits sodium reabsorption, whereas activation of insulin receptor increases sodium reabsorption in RPTs, and hyperinsulinemic animals and patients have defective renal dopaminergic system. We presume that there is an inhibition of D4 receptor on insulin receptor expression and effect, and the regulation is lost in spontaneously hypertensive rats (SHRs). Methods and ResultsInsulin receptor expression was determined by immunoblotting, and Na+‐K+‐ATPase activity was detected in both Wistar‐Kyoto (WKY) and SHR RPT cells. Stimulation of D4 receptor with PD168077 decreased expression of insulin receptors, which was blocked in the presence of the calcium‐channel blocker, nicardipine (10−6 mol/L per 24 hours), in cell culture medium without calcium or in the presence of inositol 1,4,5‐trisphosphate (IP3) receptor blocker (2‐aminoethyl diphenylborinate [2‐ADB]; 10−6 mol/L per 24 hours), indicating that extracellular calcium entry and calcium release from the endoplasmic reticulum were involved in the signal pathway. Stimulation of the insulin receptor stimulated Na+‐K+‐ATPase activity, whereas pretreatment with PD168077 for 24 hours decreased the inhibitory effects of insulin receptor on Na+‐K+‐ATPase activity in WKY cells. However, in SHR cells, inhibition of D4 receptor on insulin receptor expression and effect were lost. ConclusionsActivation of D4 receptor inhibits insulin receptor expression in RPT cells from WKY rats. The aberrant inhibition of D4 receptor on insulin receptor expression and effect might be involved in the pathogenesis of essential hypertension.https://www.ahajournals.org/doi/10.1161/JAHA.115.002448dopamine receptorhypertensioninsulinrenal proximal tubule cells |
| spellingShingle | Ye Zhang Hongmei Ren Xi Lu Duofen He Yu Han Hongyong Wang Chunyu Zeng Weibin Shi Inhibition of D4 Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule Cells Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease dopamine receptor hypertension insulin renal proximal tubule cells |
| title | Inhibition of D4 Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule Cells |
| title_full | Inhibition of D4 Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule Cells |
| title_fullStr | Inhibition of D4 Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule Cells |
| title_full_unstemmed | Inhibition of D4 Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule Cells |
| title_short | Inhibition of D4 Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule Cells |
| title_sort | inhibition of d4 dopamine receptors on insulin receptor expression and effect in renal proximal tubule cells |
| topic | dopamine receptor hypertension insulin renal proximal tubule cells |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.115.002448 |
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