Disease relevance of Npr1

• Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy [1].
• Both atrial (ANP) and brain (BNP) natriuretic peptide affect development of cardiac hypertrophy and fibrosis via binding to natriuretic peptide receptor (NPR)-A in the heart [1].
• The present study provides further evidences for altered NPR-A receptors in SHR kidney, which might act as a negative feedback in response to hypertension [2].
• Renal effects of high-dose natriuretic peptide receptor blockade in rats with congestive heart failure [3].
• Renal effects of natriuretic peptide receptor blockade in cirrhotic rats with ascites [4].

Psychiatry related information on Npr1

• In addition, using affinity cross-linking studies we have observed that water deprivation increases the expression of the 67-kDa NPR-C-like protein, and HS-142, which binds to NPR-A and the 77-kDa NPR-C-like but not the 67-kDa protein, reduced ligand internalization without affecting cAMP inhibition by ANP(1-28) [5].

High impact information on Npr1

• 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) [6].
• The heart expresses the three natriuretic peptide receptors (NPR), namely NPR-A, NPR-B, and NPR-C [6].
• Differential regulation of natriuretic peptide receptor messenger RNAs during the development of cardiac hypertrophy in the rat [6].
• Phosphorylation of the kinase homology domain is essential for activation of the A-type natriuretic peptide receptor [7].
• Therefore, rat ventricular myocytes appear to produce predominantly NPR-A [8].

Chemical compound and disease context of Npr1

• The mRNA expression of NPR-A and NPR-C was increased, whereas that of ACE and AT1 receptors was decreased in DOCA-salt hypertension [9].
• Protein kinase C(19-36) also markedly attenuated vascular hyperproliferation and hypertrophy as well as glucose-induced suppression of natriuretic peptide receptor response [10].

Biological context of Npr1

• Osmoregulation of endothelial nitric-oxide synthase gene expression in inner medullary collecting duct cells. Role in activation of the type A natriuretic peptide receptor [11].
• Tissue distribution and localization of natriuretic peptide receptor subtypes in stroke-prone spontaneously hypertensive rats [12].
• Renal ANP binding sites of NPR-A showed a lower maximal binding capacity and higher affinity in SHR than in WKY at all intrarenal sites [2].
• Patterning of renal cGMP production by the natriuretic peptide receptor type A and blood pressure in spontaneously hypertensive rats [13].
• ANF effects are mediated by NPR-A receptors coupled to guanylate cyclase and cGMP as second messenger [14].

Anatomical context of Npr1

• RESULTS: In SHR-SP aged 13 weeks, NPR-A was expressed most abundantly in the adrenal gland, lung and aorta, in that order [12].
• In the adrenal gland, NPR-A was expressed mainly in zona glomerulosa cells [12].
• NPR-B was the predominant form in the receptor guanylate cyclase family (i.e. NPR-A and NPR-B) in both rat xiphoid cartilage and in its cultured cells [15].
• Subtype switching of natriuretic peptide receptor (NPR) during in vitro culture of rat chondrocytes was demonstrated by polymerase chain reaction (PCR) analysis, receptor binding assay, and the cGMP formation method [15].
• Sodium dodecyl sulfate-polyacrylamide gel electrophoresis also identified NPR-A and NPR-C-like proteins in E16 hepatic membranes [16].

Associations of Npr1 with chemical compounds

• These data show that the inositol trisphosphate/calcium arm of the phospholipase C pathway mediates the desensitization of a natriuretic peptide receptor in A10 cells [17].
• Vasopressin-dependent inhibition of the C-type natriuretic peptide receptor, NPR-B/GC-B, requires elevated intracellular calcium concentrations [17].
• The ANG II type 1 receptor was blocked with losartan (10 mg.kg(-1).day(-1)) to investigate a possible role of the renin-angiotensin system in regulation of natriuretic peptide and NPR gene expression [1].
• Hepatic guanosine 3',5'-cyclic monophosphate production was most powerfully stimulated by ANP-(1-28), as expected for NPR-A [16].
• Similar stimulation by the two agonists was noted in spontaneously hypertensive rat (SHR) cells, paralleled by a 10-fold increase in NPR-A mRNA levels and ANP stimulation of cyclic GMP in hypertensive cells [18].

Physical interactions of Npr1

• We have previously demonstrated that atrial natriuretic factor (ANF) binding consistent with the NPR-A receptor is significantly increased in FRTL-5 cells cultured in the presence of TSH [19].
• We found that NPR-A showed a lower maximal binding capacity (B(max)) and higher affinity in SHR than in WKY rats both in the olfactory bulb and hypothalamus [20].

Regulatory relationships of Npr1

• Endothelin inhibits NPR-A and stimulates eNOS gene expression in rat IMCD cells [21].

Other interactions of Npr1

• Previous reports have shown that pressor hormones inhibit natriuretic peptide receptors NPR-A or NPR-B in a variety of different cell types [17].
• Previously, we showed that increased extracellular tonicity promotes increased type A natriuretic peptide receptor (NPR-A) expression through a p38 MAPKbeta pathway in inner medullary collecting duct cells [11].
• ANP (10(-9) and 3.10(-9)), which binds to NPR-A and NPR-C, dilated preglomerular vessels and constricted efferent arterioles similarly to that found in previous studies [22].
• Our results indicate that ANP dilates preglomerular vessels and constricts efferent arterioles through NPR-A, both responses being antagonized by A71915 with different potencies [22].
• We have shown in previous studies that high extracellular tonicity is associated with increased expression of the type A natriuretic peptide receptor (NPR-A) and reduced expression of the endothelial NO synthase (eNOS) gene in cultured rat inner-medullary collecting duct cells [21].

Analytical, diagnostic and therapeutic context of Npr1

• We have isolated and characterized three genomic clones and a genomic fragment amplified by the polymerase chain reaction that contain the rat guanylyl cyclase-A (GC-A)/atrial natriuretic peptide receptor gene [23].
• In vitro autoradiography of the binding of natriuretic peptides to E16 liver implied the presence of NPR-A and NPR-C-like receptors [16].
• METHODS: Rat VSMC were characterized with regard to natriuretic peptide receptor expression by RT/PCR and radioligand binding studies [24].
• To define further the potential domains of ANP and CNP action in brain, the present study used in situ hybridization histochemistry to map NPR-A and NPR-B mRNA-expressing cell populations [25].
• Forced homodimerization by site-directed mutagenesis alters guanylyl cyclase activity of natriuretic peptide receptor B [26].

References