Endocardial localization and characterization of natriuretic peptide binding sites in human fetal and adult heart

Rutherford, Richard A.D.; Wharton, John; Gordon, Lee; Moscoso, G.; Yacoub, Magdi H.; Polak, Julia M.

doi:10.1016/0014-2999(92)90064-b

Cited by 21 publications

(16 citation statements)

References 31 publications

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“…amplification cannot provide direct evidence for the translation of these transcripts and the distribution of the receptor proteins in the rat heart, it avoids potential problems such as "blockade" of binding sites by large amounts of ANP (and BNP) released during tissue preparation, and its ability to define specific receptor subtypes is currently unattainable with conventional ligand-binding or autoradiographical techniques using '25M-labeled compounds. One group has reported the existence of binding sites for [ (41)(42)(43)(44)47). If the natriuretic peptide receptor mRNAs we and others have detected in cardiac tissue are translated and the proteins expressed appropriately, it still remains to be established whether the effects of ANP on cardiac tissue discussed above are mediated by the known receptor types or whether there are others still to be defined, either of the "functional" guanylyl cyclase type or of a cGMP-independent form, which appear to mediate, for instance, the stimulation of amiloride-sensitive 22Na' uptake into cells in the rabbit aorta (67) and the inhibition of aldosterone secretion from adrenal cortical cells (68,69).…”

Section: Resultsmentioning

confidence: 99%

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Natriuretic peptide receptor mRNAs in the rat and human heart.

Nunez¹,

Dickson²

1992

J. Clin. Invest.

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Functional studies indicate that atrial natriuretic peptide (ANP), a member of the natriuretic peptide family, has direct effects on cardiac muscle cells. However, conventional ligandbinding studies designed to establish the presence of natriuretic peptide-binding sites in the heart have yielded conflicting results. There are discrepancies also between the latter and the receptor distribution predicted from the pattern of the mRNA transcripts localized by in situ hybridization. Here we have employed the technique of cDNA amplification with the polymerase chain reaction to confirm the presence of natriuretic peptide A, B, and C receptor mRNAs in rat and human cardiac tissue.In the rat heart, the distribution of the A and B receptor transcripts appears to be relatively homogeneous; in contrast, the C type mRNA is concentrated principally in the atria, with no difference between the left and right sides of the heart. A and B receptor DNA products were obtained after amplification of left, but not right, ventricular cDNA from the heart of a 16-yrold male with cystic fibrosis; the yield of C receptor DNA was similar for both ventricles. If these mRNA transcripts are translated into functional receptors in the rat and human heart, ANP and the other natriuretic peptides may have direct effects on cardiac function, including regulation of natriuretic peptide release via a short feedback loop, modulation of contractility of the heart, or activation of cardiac reflexes. (J. Clin. Invest.

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Section: Resultsmentioning

confidence: 99%

“…However, the interpretation of these data has been complicated by the conflicting results obtained with [12511 ANP to demonstrate specific cardiac-binding sites (37,(40)(41)(42)(43)(44)(45)(46)(47), even though the latter are easily detectable in many tissues by autoradiographical and ligand-binding techniques (48).…”

Section: Introductionmentioning

confidence: 99%

Natriuretic peptide receptor mRNAs in the rat and human heart.

Nunez¹,

Dickson²

1992

J. Clin. Invest.

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“…This compartmentalization provides the various heart regions with different abilities to bind NP and is essential for normal cardiac function, as regional alterations of NPR expression associate with a deteriorated heart performance [for references, see Cerra and Pellegrino (Cerra and Pellegrino, 2007)]. For example, NPR expressed in the ventricular EE (Wilcox et al, 1991;Rutherford et al, 1992) disappear in the presence of right ventricular hypertrophy (Kim et al, 1999), impairing EE-myocardium communications and thereby affecting contractility and contributing to cardiac damage.…”

Section: Np Receptors: a Hallmark Of Myocardial Heterogeneitymentioning

confidence: 99%

Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a ‘whip-brake’ system of the endocrine heart

Tota

Cerra

Gattuso

2010

Journal of Experimental Biology

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Summary In the past 50 years, extensive evidence has shown the ability of vertebrate cardiac non-neuronal cells to synthesize and release catecholamines (CA). This formed the mindset behind the search for the intrinsic endocrine heart properties, culminating in 1981 with the discovery of the natriuretic peptides (NP). CA and NP, co-existing in the endocrine secretion granules and acting as major cardiovascular regulators in health and disease, have become of great biomedical relevance for their potent diagnostic and therapeutic use. The concept of the endocrine heart was later enriched by the identification of a growing number of cardiac hormonal substances involved in organ modulation under normal and stress-induced conditions. Recently, chromogranin A (CgA), a major constituent of the secretory granules, and its derived cardio-suppressive and antiadrenergic peptides, vasostatin-1 and catestatin, were shown as new players in this framework, functioning as cardiac counter-regulators in ‘zero steady-state error’ homeostasis, particularly under intense excitatory stimuli, e.g. CA-induced myocardial stress. Here, we present evidence for the hypothesis that is gaining support, particularly among human cardiologists. The actions of CA, NP and CgA, we argue, may be viewed as a hallmark of the cardiac capacity to organize ‘whip-brake’ connection-integration processes in spatio-temporal networks. The involvement of the nitric oxide synthase (NOS)/nitric oxide (NO) system in this configuration is discussed. The use of fish and amphibian paradigms will illustrate the ways that incipient endocrine-humoral agents have evolved as components of cardiac molecular loops and important intermediates during evolutionary transitions, or in a distinct phylogenetic lineage, or under stress challenges. This may help to grasp the old evolutionary roots of these intracardiac endocrine/paracrine networks and how they have evolved from relatively less complicated designs. The latter can also be used as an intellectual tool to disentangle the experimental complexity of the mammalian and human endocrine hearts, suggesting future investigational avenues.

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“…The presence offunctional receptors in the heart has been suggested by several studies of the effects of natriuretic peptides on isolated myocardium or myocytes (43)(44)(45)(46). Specific cardiac binding sites for these peptides have been detected by ligand binding studies or autoradiography (47,48), but not consistently (49; D. J. Nunez, unpublished observations), possibly because of high local concentrations of endogenous ANP released during the sample preparation. However, the presence ofreceptor mRNA transcripts has now been demonstrated clearly in the monkey heart using in situ hybrid-ization (50) and in rodent and human cardiac tissue by cDNA amplification with the reverse-transcription polymerase chain reaction (RT-PCR) (51 ).…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of natriuretic peptide receptor messenger RNAs during the development of cardiac hypertrophy in the rat.

Brown

Nunez²,

Wilkins³

1993

J. Clin. Invest.

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The heart expresses the three natriuretic peptide receptors (NPR), namely NPR-A, NPR-B, and NPR-C. We have examined the temporal relationship between the expression of mRNA transcripts for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and their receptors in the heart during the development of cardiac hypertrophy in the aortovenocaval fistula rat. Messenger RNAs were measured by cDNA amplification. Progressive cardiac hypertrophy was accompanied by increased ANP mRNA prevalence throughout the heart and increased BNP mRNA in the left atrium. The most striking observation was the gradual disappearance of NPR-C transcripts (the putative "clearance" receptor) in all chambers; this was in marked contrast to the increase in mRNA levels for NPR-A and NPR-B (the guanylyl cyclase-linked receptors). Our observations have important therapeutic implications if the transcript changes are mirrored at the receptor protein level because (a) the apparent down-regulation of NPR-C may enhance the local action of natriuretic peptides on the heart, and (b) the loss of NPR-C, particularly if it is widespread, may reduce the rate of elimination of the natriuretic peptides, restricting the therapeutic potential of specific NPR-C ligands designed to reduce peptide clearance. (J. Clin. Invest. 1993.

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Endocardial localization and characterization of natriuretic peptide binding sites in human fetal and adult heart

Cited by 21 publications

References 31 publications

Natriuretic peptide receptor mRNAs in the rat and human heart.

Natriuretic peptide receptor mRNAs in the rat and human heart.

Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a ‘whip-brake’ system of the endocrine heart

Differential regulation of natriuretic peptide receptor messenger RNAs during the development of cardiac hypertrophy in the rat.

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