Disease relevance of Npr2

• Guanosine 3',5'-cyclic monophosphate levels generated by NPR-A in renal papillae and by NPR-A and NPR-B in the adrenal cortex, aorta, and mesenteric arteries of DOCA-salt-treated rats remained increased in hypertension [1].
• Hearts were then isolated and subjected to a zero-flow ischemia and reperfusion (except controls), in the absence or presence of either a B2-receptor antagonist (Hoe-140), a B1-receptor antagonist (Lys-Leu8-des-Arg9-BK), or the GC-A/GC-B-receptor antagonist (HS-142-1) [2].
• Renal inner medulla GC-B mRNA levels, but not renal CNP mRNA levels, were 3.2-fold greater in hypervolemic and 2.3-fold less in hypovolemic rats compared with euvolemic controls [3].
• The results indicate that there is a differential distribution of NPRs in the cardiac chambers, with the most abundant binding sites in RV endocardium, that NPR-B is the predominant GC-coupled NPR in ventricular endocardium, and that endocardial NPRs are downregulated with ventricular hypertrophy [4].

Psychiatry related information on Npr2

• Water deprivation significantly decreased the relative levels of CNP and NPR-B mRNA expression in both the 7- and 14-day water-deprived hopping mice, when compared to control hopping mice [5].
• The observed cross-talk of the PACAP/VIP receptors with GC-B but not with sGC may have implications for the therapy of erectile dysfunction [6].

High impact information on Npr2

• We show that a second guanylate cyclase/receptor (GC-B) exists, with distinctly different specificities for various natriuretic peptides [7].
• The deduced amino acid sequence of GC-B is 78% identical with GC-A within the intracellular region, but 43% identical within the extracellular domain [7].
• A cDNA clone encoding GC-B was isolated by low-stringency screening of a rat brain cDNA library using GC-A cDNA as a probe [7].
• 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) [8].
• Analysis by RT-PCR revealed the presence of transcripts for NPR-A as well as NPR-B and NPR-C [9].

Biological context of Npr2

• Furthermore, our data show that in the rat renal microcirculation stimulation of NPR-B results in vasodilation only, whereas NPR-C does not mediate vascular responses [10].
• The ANP antagonist A71915 (10(-9) to 10(-6)) induced moderate dilation in renal vessels possibly due to some agonistic activity on NPR-B, ANP-induced preglomerular vasodilation was attenuated by A71915 (10(-6)) to 36 +/- 6% of the initial response, whereas efferent vasoconstriction was completely abolished (-4 +/- 4% of initial response) [10].
• Binding studies were performed on membranes of COS-1 cells transfected with expression plasmids for either rat natriuretic peptide receptor (NPR)-A, rat NPR-B, or bovine NPR-C [11].
• Moreover, TSH treatment decreased C-type natriuretic peptide (CNP)-induced cGMP generation in FRTL-5 cells, suggesting a down-regulation of NPR-B [12].
• The two forms of rat GC-B differ from each other only by 75bp deletion at 3'-flanking region of the putative transmembrane domain, the shorter form lacking the nucleotide binding site by the deletion [13].

Anatomical context of Npr2

• Western blotting with affinity-purified anti-NPR-B (413-426)-Tyr revealed a polypeptide of approximately 120 kD on COS-1 cell membranes transfected with rat NPR-B cDNA [14].
• These results were supported by immunohistochemistry findings that demonstrated staining for NPR-B on papillary and medullary capillaries, glomeruli, and renal arteries [14].
• NPR-B was expressed highly in the uterus and ovary, and also in the lung, adrenal, and brain [15].
• The C-type natriuretic (CNP) peptide signals through the type B natriuretic peptide receptor (NPR-B) in vascular smooth muscle cells to activate the particulate guanylyl cyclase activity intrinsic to that receptor and raise cellular cyclic GMP levels [16].
• The same antibody detected GC-B in immunoblots of protein extracts of nonmyocytes, but not myocytes and recognized an equivalent protein in extracts of cultured cardiac fibroblasts, but not A7r5 rat smooth muscle cells [17].

Associations of Npr2 with chemical compounds

• In contrast, the cell-permeable calcium chelator, BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester), abrogates the AVP-dependent desensitization of NPR-B, and ionomycin, a calcium ionophore, mimics the AVP effect [18].
• Vasopressin-dependent inhibition of the C-type natriuretic peptide receptor, NPR-B/GC-B, requires elevated intracellular calcium concentrations [18].
• However, oxidation of the Met17 residue into methionine sulfoxide reduces the affinity of the compound for NPR-B by > 10-fold, whereas the addition of one or two iodines did not further reduce its affinity [11].
• Semiquantitative RT-PCR revealed that granulosa cells from DES- or eCG-treated animals have increased levels of NPR-B messenger RNA (mRNA) transcripts, which was in good agreement with the increased binding [19].
• To further understand the molecular significance of these regulations, we measured the relative abundance of the transcripts of NPR-A and NPR-B by Northern blot in the aorta, mesenteric arteries, adrenal cortex, renal papillae, and lungs in DOCA-salt hypertensive and control rats [1].

Other interactions of Npr2

• Previous reports have shown that pressor hormones inhibit natriuretic peptide receptors NPR-A or NPR-B in a variety of different cell types [18].
• The purpose of the present study was to determine whether TSH treatment, therefore, results in higher levels of ANF-induced intracellular cGMP, and whether TSH elicits similar effects on cGMP signaling through the NPR-B receptor [12].
• TGF-beta 1 decreased both NPR-A and NPR-B mRNA levels with a predominant effect in SHR cells at high cell density.(ABSTRACT TRUNCATED AT 250 WORDS)[20]

Analytical, diagnostic and therapeutic context of Npr2

• 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 [21].
• Radioimmunoassay and RNase protection analyses revealed passage-associated increase in CNP-like immunoreactivity and in levels of NPR-B mRNA, respectively [22].
• Using a semi-quantitative multiplex PCR technique, the expression of renal CNP and NPR-B mRNA was determined in 7- and 14-day water-deprived hopping mice, in parallel with control hopping mice (access to water) [5].
• GC-A and GC-B receptors were detected using quantitative autoradiography after application of either [125I]ANP or [125I]-tyr0CNP to sections of frozen ovaries [23].
• These results indicate that GC-B, CNP specific receptor/guanylyl cyclase, is expressed at the sites of vascular injury, and that CNP might be efficacious in the prevention of restenosis caused by intimal thickening following coronary angioplasty [24].

References