Differential expression and synthesis of natriuretic peptides determines natriuretic peptide receptor expression in primary cultures of human proximal tubular cells

S. K. Mistry, Gabrielle Margaret Hawksworth, James Stuart McLay, A. D. Struthers

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Introduction The natriuretic peptides and natriuretic peptide receptors may play a beneficial role in hypertension and heart failure and possibly in opposing associated detrimental cellular changes in the heart, vasculature and kidney. These responses may be, in part, modulated by the natriuretic peptide clearance receptor rather than the natriuretic peptide receptors (NPR-A or NPR-B),

Objective To investigate the expression of the natriuretic peptide receptors (NPR-A,-B,-C) and the natriuretic peptides (ANP, BNP, CNP) in primary cultures of human proximal tubular cells and the role played by endogenously released natriuretic peptides in natriuretic peptide receptor expression.

Results Northern analysis demonstrated that freshly isolated human proximal tubular cells express the NPR-C only. However, at confluence mRNA transcripts for both the NPR-A and -B were expressed, accompanied by a significant cyclic guanosine monophosphate (cGMP) response to ANP and CNP, indicating the development of functionally active receptors, A significant increase in immunoreactive ANP, BNP and CNP in the cell supernatant accompanied the appearance of these receptors. incubation of freshly isolated cells with exogenous ANP, BNP, CNP or with the NPR-C specific ligand C((4-23))ANF induced similar changes in receptor expression, suggesting that these changes were mediated via the NPR-C rather than the NPR-A or -B,

Conclusions Significant changes in peptide and receptor expression occur during cell culture and may be integrally linked, with functionally active NPR-A and -B occurring in response to an increase in the expression of the natriuretic peptides possibly acting at the NPR-C. (C) 2001 Lippincott Williams & Wilkins.

Original languageEnglish
Pages (from-to)255-262
Number of pages7
JournalJournal of Hypertension
Volume19
Issue number2
DOIs
Publication statusPublished - 2001

Keywords

  • natriuretic peptides
  • natriuretic peptide receptor
  • ANP
  • BNP
  • CNP
  • cell culture
  • human proximal tubular cells
  • NPR-A
  • NPR-B
  • NPR-C
  • SMOOTH-MUSCLE CELLS
  • ENDOTHELIAL-CELLS
  • DOWN-REGULATION
  • C-RECEPTOR
  • PROLIFERATION
  • KIDNEY
  • BRAIN
  • POLYPEPTIDE
  • STIMULATION
  • INHIBITION

Cite this

Differential expression and synthesis of natriuretic peptides determines natriuretic peptide receptor expression in primary cultures of human proximal tubular cells. / Mistry, S. K.; Hawksworth, Gabrielle Margaret; McLay, James Stuart; Struthers, A. D.

In: Journal of Hypertension, Vol. 19, No. 2, 2001, p. 255-262.

Research output: Contribution to journalArticle

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title = "Differential expression and synthesis of natriuretic peptides determines natriuretic peptide receptor expression in primary cultures of human proximal tubular cells",
abstract = "Introduction The natriuretic peptides and natriuretic peptide receptors may play a beneficial role in hypertension and heart failure and possibly in opposing associated detrimental cellular changes in the heart, vasculature and kidney. These responses may be, in part, modulated by the natriuretic peptide clearance receptor rather than the natriuretic peptide receptors (NPR-A or NPR-B),Objective To investigate the expression of the natriuretic peptide receptors (NPR-A,-B,-C) and the natriuretic peptides (ANP, BNP, CNP) in primary cultures of human proximal tubular cells and the role played by endogenously released natriuretic peptides in natriuretic peptide receptor expression.Results Northern analysis demonstrated that freshly isolated human proximal tubular cells express the NPR-C only. However, at confluence mRNA transcripts for both the NPR-A and -B were expressed, accompanied by a significant cyclic guanosine monophosphate (cGMP) response to ANP and CNP, indicating the development of functionally active receptors, A significant increase in immunoreactive ANP, BNP and CNP in the cell supernatant accompanied the appearance of these receptors. incubation of freshly isolated cells with exogenous ANP, BNP, CNP or with the NPR-C specific ligand C((4-23))ANF induced similar changes in receptor expression, suggesting that these changes were mediated via the NPR-C rather than the NPR-A or -B,Conclusions Significant changes in peptide and receptor expression occur during cell culture and may be integrally linked, with functionally active NPR-A and -B occurring in response to an increase in the expression of the natriuretic peptides possibly acting at the NPR-C. (C) 2001 Lippincott Williams & Wilkins.",
keywords = "natriuretic peptides, natriuretic peptide receptor, ANP, BNP, CNP, cell culture, human proximal tubular cells, NPR-A, NPR-B, NPR-C, SMOOTH-MUSCLE CELLS, ENDOTHELIAL-CELLS, DOWN-REGULATION, C-RECEPTOR, PROLIFERATION, KIDNEY, BRAIN, POLYPEPTIDE, STIMULATION, INHIBITION",
author = "Mistry, {S. K.} and Hawksworth, {Gabrielle Margaret} and McLay, {James Stuart} and Struthers, {A. D.}",
year = "2001",
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TY - JOUR

T1 - Differential expression and synthesis of natriuretic peptides determines natriuretic peptide receptor expression in primary cultures of human proximal tubular cells

AU - Mistry, S. K.

AU - Hawksworth, Gabrielle Margaret

AU - McLay, James Stuart

AU - Struthers, A. D.

PY - 2001

Y1 - 2001

N2 - Introduction The natriuretic peptides and natriuretic peptide receptors may play a beneficial role in hypertension and heart failure and possibly in opposing associated detrimental cellular changes in the heart, vasculature and kidney. These responses may be, in part, modulated by the natriuretic peptide clearance receptor rather than the natriuretic peptide receptors (NPR-A or NPR-B),Objective To investigate the expression of the natriuretic peptide receptors (NPR-A,-B,-C) and the natriuretic peptides (ANP, BNP, CNP) in primary cultures of human proximal tubular cells and the role played by endogenously released natriuretic peptides in natriuretic peptide receptor expression.Results Northern analysis demonstrated that freshly isolated human proximal tubular cells express the NPR-C only. However, at confluence mRNA transcripts for both the NPR-A and -B were expressed, accompanied by a significant cyclic guanosine monophosphate (cGMP) response to ANP and CNP, indicating the development of functionally active receptors, A significant increase in immunoreactive ANP, BNP and CNP in the cell supernatant accompanied the appearance of these receptors. incubation of freshly isolated cells with exogenous ANP, BNP, CNP or with the NPR-C specific ligand C((4-23))ANF induced similar changes in receptor expression, suggesting that these changes were mediated via the NPR-C rather than the NPR-A or -B,Conclusions Significant changes in peptide and receptor expression occur during cell culture and may be integrally linked, with functionally active NPR-A and -B occurring in response to an increase in the expression of the natriuretic peptides possibly acting at the NPR-C. (C) 2001 Lippincott Williams & Wilkins.

AB - Introduction The natriuretic peptides and natriuretic peptide receptors may play a beneficial role in hypertension and heart failure and possibly in opposing associated detrimental cellular changes in the heart, vasculature and kidney. These responses may be, in part, modulated by the natriuretic peptide clearance receptor rather than the natriuretic peptide receptors (NPR-A or NPR-B),Objective To investigate the expression of the natriuretic peptide receptors (NPR-A,-B,-C) and the natriuretic peptides (ANP, BNP, CNP) in primary cultures of human proximal tubular cells and the role played by endogenously released natriuretic peptides in natriuretic peptide receptor expression.Results Northern analysis demonstrated that freshly isolated human proximal tubular cells express the NPR-C only. However, at confluence mRNA transcripts for both the NPR-A and -B were expressed, accompanied by a significant cyclic guanosine monophosphate (cGMP) response to ANP and CNP, indicating the development of functionally active receptors, A significant increase in immunoreactive ANP, BNP and CNP in the cell supernatant accompanied the appearance of these receptors. incubation of freshly isolated cells with exogenous ANP, BNP, CNP or with the NPR-C specific ligand C((4-23))ANF induced similar changes in receptor expression, suggesting that these changes were mediated via the NPR-C rather than the NPR-A or -B,Conclusions Significant changes in peptide and receptor expression occur during cell culture and may be integrally linked, with functionally active NPR-A and -B occurring in response to an increase in the expression of the natriuretic peptides possibly acting at the NPR-C. (C) 2001 Lippincott Williams & Wilkins.

KW - natriuretic peptides

KW - natriuretic peptide receptor

KW - ANP

KW - BNP

KW - CNP

KW - cell culture

KW - human proximal tubular cells

KW - NPR-A

KW - NPR-B

KW - NPR-C

KW - SMOOTH-MUSCLE CELLS

KW - ENDOTHELIAL-CELLS

KW - DOWN-REGULATION

KW - C-RECEPTOR

KW - PROLIFERATION

KW - KIDNEY

KW - BRAIN

KW - POLYPEPTIDE

KW - STIMULATION

KW - INHIBITION

U2 - 10.1097/00004872-200102000-00012

DO - 10.1097/00004872-200102000-00012

M3 - Article

VL - 19

SP - 255

EP - 262

JO - Journal of Hypertension

JF - Journal of Hypertension

SN - 0263-6352

IS - 2

ER -