title: Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA.
abstract: Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of l-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension.
authors: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Centre, Peking Union Medical, Beijing, China.|Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors: Xiaoliang
authors: X
authors: Jiang
authors: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Centre, Peking Union Medical, Beijing, China.
authors: Yanrong
authors: Y
authors: Zhang
authors: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; yangzhiwei@cnilas.pumc.edu.cn.|Department of Pathology, The University of Texas Medical Branch, Galveston, Texas.
authors: Yu
authors: Y
authors: Yang
authors: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; yangzhiwei@cnilas.pumc.edu.cn.|Department of Cardiology, Daping Hospital, The Third Military Medical University and Chongqing Institute of Cardiology, Chongqing, China.
authors: Jian
authors: J
authors: Yang
authors: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors: Laureano D
authors: LD
authors: Asico
authors: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Centre, Peking Union Medical, Beijing, China.
authors: Wei
authors: W
authors: Chen
authors: Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia.
authors: Robin A
authors: RA
authors: Felder
authors: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors: Ines
authors: I
authors: Armando
authors: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.|Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland.|Department of Medicine, Division of Kidney Disease and Hypertension, The George Washington University School of Medicine and Health Sciences, Washington, DC; and.|Department of Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC.
authors: Pedro A
authors: PA
authors: Jose
authors: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Centre, Peking Union Medical, Beijing, China; yangzhiwei@cnilas.pumc.edu.cn.
authors: Zhiwei
authors: Z
authors: Yang
mesh_terms: D027241:Amino Acid Transport System y+L / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004298:Dopamine / Q000096:biosynthesis* / Q000652:urine; D015536:Down-Regulation; D005755:Gastrins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D020868:Gene Silencing; D006801:Humans; D015151:Immunoblotting; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D043887:Receptor, Cholecystokinin B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D027241:Amino Acid Transport System y+L; D005755:Gastrins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D043887:Receptor, Cholecystokinin B; D007980:Levodopa; D004298:Dopamine
keywords: dopamine; gastrin; hypertension; l-DOPA; l-type amino acid transporter