Natriuretic peptide clearance receptor is transcriptionally down-regulated by β2-adrenergic stimulation in vascular smooth muscle cells

Ichiro Kishimoto, Takaaki Yoshimasa, Shin Ichi Suga, Yoshihiro Ogawa, Yasato Komatsu, Osamu Nakagawa, Hiroshi Itoh, Kazuwa Nakao

Research output: Contribution to journalArticle

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Abstract

Three natriuretic peptide receptors (the ANP-A, ANP-B, and clearance (C) receptors) have been reported. The regulation of these receptors by catecholamines was examined in cultured rat vascular smooth muscle cells. Treatment with norepinephrine decreased the maximum 125I-ANP binding. The competitive binding assay with des[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4-23)-NH2 (C-ANF-4-23), a specific ligand for the C receptor, revealed that the decrease in the 125I-ANP binding by norepinephrine was caused by the down-regulation of the C receptor. Isoproterenol also down-regulated the C receptor in a time- and dose-dependent manner. The catecholamine-induced down-regulation of the C receptor was antagonized by a β2-selective adrenergic antagonist, ICI 118,551 but not by an α1-, α2-, or β1-adrenergic antagonist. Forskolin, NaF and, 8-bromo-cyclic AMP also decreased the C receptor density. The isoproterenol-induced decrease in the C receptor level was further confirmed by affinity cross-linking and Western blot analysis. Northern blot analysis revealed that isoproterenol and 8-bromo-cyclic AMP decreased the steady- state level of C receptor mRNA. By contrast, neither the ANP-A receptor nor the ANP-B receptor mRNA level was affected by 8-bromo-cyclic AMP. The nuclear run-on assay showed that the transcriptional rate of the C receptor gene was decreased by isoproterenol, whereas those of the ANP-A and ANP-B receptor genes were unchanged. Isoproterenol attenuated the clearance of exogenously added ANP and augmented the ANP-stimulated intracellular cyclic GMP production to the same extent as the selective occupancy of the C receptor with C-ANF-(4-23), suggesting that the isoproterenol-induced enhancement of responsiveness to ANP could result not from the sensitization of the ANP-A or ANP-B receptor but from the down-regulation of the C receptor, which leads to the attenuated clearance of ANP. These findings suggest that the β2- adrenergic receptor stimulation down-regulates the C receptor through the decrease in the transcriptional rate of the C receptor gene and that the activation of the sympathetic nervous system augments the biological responsiveness to natriuretic peptides by attenuating their metabolic clearance in vascular walls.

Original languageEnglish
Pages (from-to)28300-28308
Number of pages9
JournalJournal of Biological Chemistry
Volume269
Issue number45
Publication statusPublished - Nov 11 1994
Externally publishedYes

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Natriuretic Peptides
Peptide Receptors
Atrial Natriuretic Factor
Vascular Smooth Muscle
Adrenergic Agents
Smooth Muscle Myocytes
Muscle
Cells
Isoproterenol
Atrial Natriuretic Factor Receptors
8-Bromo Cyclic Adenosine Monophosphate
Down-Regulation
Adrenergic Antagonists
Genes
Norepinephrine
Catecholamine Receptors
Assays
Messenger RNA
Competitive Binding
Sympathetic Nervous System

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Natriuretic peptide clearance receptor is transcriptionally down-regulated by β2-adrenergic stimulation in vascular smooth muscle cells. / Kishimoto, Ichiro; Yoshimasa, Takaaki; Suga, Shin Ichi; Ogawa, Yoshihiro; Komatsu, Yasato; Nakagawa, Osamu; Itoh, Hiroshi; Nakao, Kazuwa.

In: Journal of Biological Chemistry, Vol. 269, No. 45, 11.11.1994, p. 28300-28308.

Research output: Contribution to journalArticle

Kishimoto, I, Yoshimasa, T, Suga, SI, Ogawa, Y, Komatsu, Y, Nakagawa, O, Itoh, H & Nakao, K 1994, 'Natriuretic peptide clearance receptor is transcriptionally down-regulated by β2-adrenergic stimulation in vascular smooth muscle cells', Journal of Biological Chemistry, vol. 269, no. 45, pp. 28300-28308.
Kishimoto, Ichiro ; Yoshimasa, Takaaki ; Suga, Shin Ichi ; Ogawa, Yoshihiro ; Komatsu, Yasato ; Nakagawa, Osamu ; Itoh, Hiroshi ; Nakao, Kazuwa. / Natriuretic peptide clearance receptor is transcriptionally down-regulated by β2-adrenergic stimulation in vascular smooth muscle cells. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 45. pp. 28300-28308.
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abstract = "Three natriuretic peptide receptors (the ANP-A, ANP-B, and clearance (C) receptors) have been reported. The regulation of these receptors by catecholamines was examined in cultured rat vascular smooth muscle cells. Treatment with norepinephrine decreased the maximum 125I-ANP binding. The competitive binding assay with des[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4-23)-NH2 (C-ANF-4-23), a specific ligand for the C receptor, revealed that the decrease in the 125I-ANP binding by norepinephrine was caused by the down-regulation of the C receptor. Isoproterenol also down-regulated the C receptor in a time- and dose-dependent manner. The catecholamine-induced down-regulation of the C receptor was antagonized by a β2-selective adrenergic antagonist, ICI 118,551 but not by an α1-, α2-, or β1-adrenergic antagonist. Forskolin, NaF and, 8-bromo-cyclic AMP also decreased the C receptor density. The isoproterenol-induced decrease in the C receptor level was further confirmed by affinity cross-linking and Western blot analysis. Northern blot analysis revealed that isoproterenol and 8-bromo-cyclic AMP decreased the steady- state level of C receptor mRNA. By contrast, neither the ANP-A receptor nor the ANP-B receptor mRNA level was affected by 8-bromo-cyclic AMP. The nuclear run-on assay showed that the transcriptional rate of the C receptor gene was decreased by isoproterenol, whereas those of the ANP-A and ANP-B receptor genes were unchanged. Isoproterenol attenuated the clearance of exogenously added ANP and augmented the ANP-stimulated intracellular cyclic GMP production to the same extent as the selective occupancy of the C receptor with C-ANF-(4-23), suggesting that the isoproterenol-induced enhancement of responsiveness to ANP could result not from the sensitization of the ANP-A or ANP-B receptor but from the down-regulation of the C receptor, which leads to the attenuated clearance of ANP. These findings suggest that the β2- adrenergic receptor stimulation down-regulates the C receptor through the decrease in the transcriptional rate of the C receptor gene and that the activation of the sympathetic nervous system augments the biological responsiveness to natriuretic peptides by attenuating their metabolic clearance in vascular walls.",
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N2 - Three natriuretic peptide receptors (the ANP-A, ANP-B, and clearance (C) receptors) have been reported. The regulation of these receptors by catecholamines was examined in cultured rat vascular smooth muscle cells. Treatment with norepinephrine decreased the maximum 125I-ANP binding. The competitive binding assay with des[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4-23)-NH2 (C-ANF-4-23), a specific ligand for the C receptor, revealed that the decrease in the 125I-ANP binding by norepinephrine was caused by the down-regulation of the C receptor. Isoproterenol also down-regulated the C receptor in a time- and dose-dependent manner. The catecholamine-induced down-regulation of the C receptor was antagonized by a β2-selective adrenergic antagonist, ICI 118,551 but not by an α1-, α2-, or β1-adrenergic antagonist. Forskolin, NaF and, 8-bromo-cyclic AMP also decreased the C receptor density. The isoproterenol-induced decrease in the C receptor level was further confirmed by affinity cross-linking and Western blot analysis. Northern blot analysis revealed that isoproterenol and 8-bromo-cyclic AMP decreased the steady- state level of C receptor mRNA. By contrast, neither the ANP-A receptor nor the ANP-B receptor mRNA level was affected by 8-bromo-cyclic AMP. The nuclear run-on assay showed that the transcriptional rate of the C receptor gene was decreased by isoproterenol, whereas those of the ANP-A and ANP-B receptor genes were unchanged. Isoproterenol attenuated the clearance of exogenously added ANP and augmented the ANP-stimulated intracellular cyclic GMP production to the same extent as the selective occupancy of the C receptor with C-ANF-(4-23), suggesting that the isoproterenol-induced enhancement of responsiveness to ANP could result not from the sensitization of the ANP-A or ANP-B receptor but from the down-regulation of the C receptor, which leads to the attenuated clearance of ANP. These findings suggest that the β2- adrenergic receptor stimulation down-regulates the C receptor through the decrease in the transcriptional rate of the C receptor gene and that the activation of the sympathetic nervous system augments the biological responsiveness to natriuretic peptides by attenuating their metabolic clearance in vascular walls.

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