Effect of D_(4)Dopamine Receptor on Na^(+)-K^(+)-ATPase Activity in Renal Proximal Tubule Cells  

作　　者：Duofen He Hongmei Ren Hongyong Wang Pedro A.Jose Chunyu Zeng Tianyang Xia Jian Yang 

机构地区：[1]Department of Cardiology,Daping Hospital,The Third Military Medical University,Chongqing 400042,China [2]Chongqing Institute of Cardiology&,Chongqing Key Laboratory of Hypertension Research,Chongqing 400042,China [3]Division of Renal Diseases&,Hypertension,Department of Medicine and Department of Physiology and Pharmacology,The George Washington University School of Medicine&,Health Sciences,Washington,District of Columbia 20052,USA [4]Research Center for Metabolic and Cardiovascular Diseases,The Third Affiliated Hospital of Chongqing Medical University,Chongqing 410020,China [5]Department of Clinical Nutrition,The Third Affiliated Hospital of Chongqing Medical University,Chongqing 410020,China

出　　处：《Cardiology Discovery》2023年第1期24-29,共6页心血管病探索（英文）

基　　金：the National Key R&D Program of China(2018YFC1312700);the National Naturai Science Foundation of China(831730043);the Program of Innovative Research Team of the National Natural Science Foundation(81721001);Program for Changjiang Scholars and Innovative Research Team in University(IRT1216);Key Research and Development Projects of Science and Technology Innovation of Social and People's Livelihood in Chongqing City,(cstc2018jscx-mszdX0024);Clinical Medical Research Talent Training Program from The Third Military Medical University(2018XLCi012);National Institutes of Health,USA(P01HL074940,DK039308,and DK119652).

摘　　要：Objective:Dopamine,via its receptors,plays a vital role in the maintenance of blood pressure by modulating renal sodium transport.However,the role of the D_(4)dopamine receptor(D_(4)receptor)in renal proximal tubules(PRTs)is still unclear.This study aimed to verify the hypothesis that activation of D_(4)receptor directly inhibits the activity of the Na+-K+-ATPase(NKA)in RPT cells.Methods:NKA activity,nitric oxide(NO)and cyclic guanosine monophosphate(cGMP)levels were measured in RPT cells treated with the D_(4)receptor agonist PD168077 and/or the D_(4)receptor antagonist L745870,the NO synthase inhibitor NG-nitro-L-arginine-methyl ester(L-NAME)or the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one(ODQ).Total D_(4)receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto(WKY)rats and spontaneously hypertensive rats(SHRs).Results:Activation of D_(4)receptors with PD168077,inhibited NKA activity in RPT cells from WKY rats in a concentration-and time-dependent manner.The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D_(4)receptor antagonist L745870,which by itself had no effect.The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ,which by themselves had no effect on NKA activity,eliminated the inhibitory effect of PD168077 on NKA activity.Activation of D_(4)receptors also increased NO levels in the culture medium and cGMP levels in RPT cells.However,the inhibitory effect of D_(4)receptors on NKA activity was absent in RPT cells from SHRs,which could be related to decreased plasma membrane expression of D_(4)receptors in SHR RPT cells.Conclusions:Activation of D_(4)receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs.Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.

关 键 词：Sodium-potassium-exchanging ATPASE DOPAMINE D_(4) receptor RENAL PROXIMAL TUBULE Kidney Hypertension 

分 类 号：R544.1[医药卫生—心血管疾病]