Physiological Role of Silent Receptors of Atrial Natriuretic Factor

Maack, Thomas; Suzuki, Muneya; Almeida, Fernando Antônio de; Nussenzveig, Daniel R.; Scarborough, Robert M.; McEnroe, Glenn; Lewicki, John

doi:10.1126/science.2823385

Cited by 913 publications

(405 citation statements)

References 23 publications

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“…However, the possible mechanisms for the cardioprotective effects of the three natriuretic peptides on I/R seem to be controversial. NPRC activation is thought to be responsible for the cardioprotective role of CNP as mentioned above, and the selective agonist of NPRC (cANF [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] ) also reduces infarct size and maintains coronary perfusion pressure [12]. Studies of ANP and BNP effects show the involvement of cGMP generated via the NPRA receptor in the reduction of infarct size [24,25].…”

Section: Discussionmentioning

confidence: 99%

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Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

Wang

Waard

Sterner-Kock

et al. 2007

European J of Heart Fail

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Objective: Infused C-type natriuretic peptide (CNP) was recently found to play a cardioprotective role in preventing myocardial ischaemia/ reperfusion (I/R) injury and improving cardiac remodelling after myocardial infarction (MI) in rats. Our study aimed to investigate the effect of cardiomyocyte-specific CNP over-expression on I/R injury and MI in transgenic mice. Methods and results:We generated transgenic (TG) mice over-expressing CNP in cardiomyocytes. Elevated CNP expression on RNA and protein levels was demonstrated by RNase-protection assay and radioimmunoassay. Male TG mice and age-matched wild-type (WT) littermates were subjected to 1-hour global myocardial ischaemia and 23 h of reperfusion or permanent ligation of the coronary artery for 3 weeks.Infarct size did not differ between the WT and TG groups in mice subjected to I/R. In mice that underwent permanent ligation of coronary arteries, both left and right ventricular hypertrophy were prevented by CNP over-expression 3 weeks post-MI. Histological analysis revealed less necrosis, muscular degeneration and inflammation in infarcted TG mice. Impairment of cardiac function was less pronounced in transgenic animals than in the wild-type controls. Conclusions: Over-expression of CNP in cardiomyocytes does not affect I/R-induced infarct size but prevents cardiac hypertrophy induced by MI. Therefore, CNP may represent a potent therapeutic target for the treatment of patients with cardiac hypertrophy induced by myocardial infarction or other aetiology.

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Section: Discussionmentioning

confidence: 99%

“…ANP and BNP are ligands of NPRA, while CNP preferentially binds to NPRB. NPRC has similar affinity to all three natriuretic peptides and is commonly considered a clearance receptor [8,9].…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

Wang

Waard

Sterner-Kock

et al. 2007

European J of Heart Fail

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“…In theory, at least, such combined NEP\ACE inhibitors should provide benefits beyond ACE inhibition alone. An alternative approach, yet to be assessed in man, is to augment endogenous circulating levels of ANP and BNP through blockade of receptors that normally contribute to clearance of the peptides from plasma [8].…”

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confidence: 99%

Cardiac natriuretic peptides as predictors of mortality

Lainchbury¹,

Espiner²,

Frampton³

et al. 1997

Journal of Internal Medicine

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“…Maack and his co-workers have reported that ANP-R2 is biologically silent and the most important role of this receptor is clearance of ANP acts as a hormonal buffer system to modulate its plasma levels, thus being called a clearance receptor [9]. However, Cantin and colleagues have recently reported that ANP-R2 is coupled to the adenylate cyclase/cAMP system through an inhibitory guanine-nucleotide-binding regulatory protein (Gi), leading to a decrease in the intracellular cAMP level [lo].…”

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confidence: 99%

An oxidized analog of α‐human atrial natriuretic polypeptide is a selective agonist for the atrial‐natriuretic‐polypeptide clearance receptor which lacks a guanylate cyclase

Koyama

Terai

Inoue

et al. 1992

European Journal of Biochemistry

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The differences in biological functions between a-human atrial natriuretic polypeptide (a-hANP) and its oxidized analog, MetSO-a-hANP, have been investigated. Analysis of the ANP receptor subtypes by affinity labeling has shown that a bovine pulmonary aortic endothelial cell line (CPAE cells) primarily expresses ANP-R1 (R, receptor) coupled to particulate guanylate cyclase, while Hela cells from human cervical carcinoma predominantly express ANP-R2, which lacks a guanylate cyclase. a-hANP could bind to both ANP receptor subtypes with high affinity, while MetSO-a-hANP showed more selective binding to ANP-R2 than to ANP-RI . The activity of MetSO-a-hANP for stimulation of guanylate cyclase coupled to ANP-R1 was about 520-fold less than that of a-hANP (median effective dose = 2.5 nM for a-hANP, 1.3 pM for MetSO-a-hANP), indicating that MetSO-a-hANP was a partial agonist for this receptor. While this oxidized analog could inhibit the cAMP production through ANP-R2, with 0.15 times the activity of a-hANP (median concentration = 0.31 nM for a-hANP, 2.0 nM for MetSO-a-hANP). In in vivo studies, the diuretic activity of MetSO-a-hANP was 25 -100-fold less than that of a-hANP. In addition, MetSO-a-hANP could potentiate the diuretic activity of a-hANP that was also caused by C-ANF4-,,, a specific agonist for ANP-R2.These results demonstrate that MetSO-a-hANP can act as an agonist more selective for ANP-R2 than for ANP-Rl, both in vivo and in vitro. The relationship between receptor selectivities and the conformation of a-hANP or MetSO-a-hANP was also discussed.Atrial natriuretic polypeptides (ANP) are peptide hormones regulating the fluid balance, electrolyte balance, blood pressure and the renin-angiotensin system [l]. ANP evoke their biological activities by interacting with receptors expressed on a cell surface. Two subclasses of ANP receptors, ANP-R1 and ANP-R2, have been isolated and their cDNA have been cloned [2-61. ANP-R1 is a single-chain glycoprotein with a molecular mass of 130 kDa containing a particulate guanylate cyclase in its intracellular domain [7]. The interaction of ANP with ANP-R1 results in the activation of its guanylate cyclase and increases the intracellular cGMP level [l, 51. It is well accepted that cGMP acts as a second messenger for the biological activity of ANP, at least for vasorelaxation, diuresis and natriuresis 11, 81. ANP-R, is a homodimer of two 65 kDa glycoproteins linked by disulfide bonds which lack a guanylate cyclase and is more abundant than ANP-R1 in various tissues 111.Correspondence to S. Koyama and M . Kobayashi, Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 1 -6, a-Chome, Kashima, Yodogawa-ku, Osaka, Japan 532Abbreviations. ANP, atrial natriuretic polypeptide; u-hANP, a-human ANP; B,,,, density of receptors; DMEM, Dulbecco's modified Eagle's medium; Gi, inhibitory guanine-nucleotide-binding regulatory protein; R, receptor; ICs0, median inhibitory concentration; ED,o, median effective dose.Maack and his co-workers have reported that ANP-R2 is biologically silent an...

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Physiological Role of Silent Receptors of Atrial Natriuretic Factor

Cited by 913 publications

References 23 publications

Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

Cardiomyocyte‐restricted over‐expression of C‐type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice

Cardiac natriuretic peptides as predictors of mortality

An oxidized analog of α‐human atrial natriuretic polypeptide is a selective agonist for the atrial‐natriuretic‐polypeptide clearance receptor which lacks a guanylate cyclase

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