Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The natriuretic peptide system comprises at least three endogenous ligands, namely, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), and three receptors for natriuretic peptides (NPR), that is, NPR-A, NPR-B and clearance receptor (NPR-C). Three natriuretic peptides derived from the distinct genes share a common ring structure with 17 amino acids formed by a disulfide linkage which confers the unique biological property on these peptides. ANP and BNP are elucidated to be the cardiac hormone mainly secreted from the atrium, and from the ventricle, respectively. CNP, first recognized as the neuropeptide, is now identified within the vascular wall, especially in endothelial cells and considered to be the peptidic endothelium-derived relaxing factor (EDRF). While NPR-A shows the high affinity to ANP and BNP, NPR-B is the selective receptor for CNP. These two types of "biologically active" NPR are the membrane-bound guanylate cyclase itself, and mediate the wide range of biological actions of natriuretic peptides through cyclic GMP-dependent cascade. The clearance receptor shows the ligand-binding affinity with the rank order of ANP > CNP > BNP and is considered to be involved in the clearance of the peptides. The natriuretic peptide system as an endocrine and paracrine/autocrine system serves as one of the key modulatory systems for blood pressure, body fluid homeostasis and vascular remodeling.
...
PMID:[Molecular biology and pharmacology of natriuretic peptide system]. 810 May 90

We have observed different ATP interactions in two guanylate cyclase (GC)-coupled natriuretic peptide (NP) receptor subtypes, designated NPR-A and NPR-B. The NPR-A is selectively expressed by LLC-PK1 epithelial cells and the NPR-B by NIH-3T3 fibroblast cells. In LLC-PK1 membranes, ATP-Mg2+ potentiated ANP-stimulated GC activity (ANP-s-GC). In contrast, in NIH-3T3 membranes, ATP-Mg2+ inhibited ANP-s-GC but enhanced CNP-stimulated GC activity (CNP-s GC). ATP in the presence of Mn2+ inhibited LLC-PK1 and NIH-3T3 membrane ANP-s-GC and CNP-s-GC. These are the first data suggesting that the ATP-Mg2+ produces different effects between membrane NPR-A and -B subtypes. We have also demonstrated that GC of NPR-B is sensitive to methylene blue.
...
PMID:Different ATP effects on natriuretic peptide receptor subtypes in LLC-PK1 and NIH-3T3 cells. 810 67

The type C receptor (ANP-C or NPR-C) for the natriuretic peptides was demonstrated, by site-directed mutagenesis, to have an immunoglobulin-like disulfide bonding pattern that is very similar to that of the cytokine receptor superfamily. The mature form of ANP-C has a disulfide-linked homodimeric structure and contains 5 conserved cysteine residues per subunit, all in the extracellular domain. To identify the cysteine residue involved in the dimerization and further to determine the intramolecular disulfide bridges and their functional roles, cysteine to serine mutations of the 5 cysteine residues were constructed. An analysis of the mutant receptors expressed in COS-1 cells by 125I-ANP binding assay and by measuring difference in their electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gels indicated that 1) the first 4 cysteine residues are joined sequentially, forming the Cys104-Cys132 and Cys209-Cys257 loops of 29 and 49 residues, respectively; 2) the two disulfide-linked loops are essential for the ligand binding activity; 3) the 5th cysteine residue Cys469 is used in the formation of covalently linked dimers; and 4) the covalent association of the subunit through the disulfide bond involving Cys469 has no apparent influence on ligand-receptor interactions. The intramolecular disulfide bond Cys104-Cys132 was also confirmed by direct protein sequencing of tryptic fragments of purified ANP-C receptor. The secondary structural features revealed here will be useful in understanding the structure and function relationships of not only the dimeric ANP-C receptor, which has only a short cytoplasmic tail, but also the ANP-A (GC-A) and ANP-B (GC-B) receptor subtypes, which have a guanylate cyclase domain in their long cytoplasmic tail and have recently been shown to possess an oligomeric structure, since they have similarly spaced cysteine residues in their extracellular domains.
...
PMID:Mutational analysis of disulfide bridges in the type C atrial natriuretic peptide receptor. 813 55

Receptors for the natriuretic peptide family have been characterized in the adrenocorticotrophic hormone (ACTH)-secreting AtT-20 pituitary tumour cell line. Northern blot analysis detected mRNA transcripts for the guanylate cyclase-linked GC-B receptor subtype. There was no evidence for the expression of either guanylate cyclase-linked GC-A receptor or atrial natriuretic peptide (ANP)-C (clearance) receptor mRNAs. Cyclic GMP production in AtT-20 cells was stimulated up to 200-fold by C-type natriuretic peptide (CNP), which was 10- and 20 times as effective as equivalent concentrations of brain natriuretic peptide and ANP respectively. Cyclic GMP dose-response curves to CNP failed to show any signs of saturation even at concentrations up to 30 microM, indicating a relatively low affinity of CNP for the GC-B receptor. Although CNP induced large stimulations in cyclic GMP production, specific binding of [125I-Tyr0]CNP could not be demonstrated in AtT-20 cells. The absence of specific binding with this radiolabelled analogue is possibly due to a reduced affinity for the GC-B receptor, as CNP analogues with N-terminal modifications such as [Tyr0]CNP and [127I-Tyr0]CNP exhibited reduced abilities to stimulate cyclic GMP production in these cells. Despite elevating cyclic GMP levels, CNP had no effect on basal or corticotrophin-releasing factor-stimulating ACTH release from the cells. These results show that the guanylate cyclase-coupled GC-B receptor is the only natriuretic peptide receptor subtype expressed in AtT-20 cells. Although CNP can markedly stimulate cyclic GMP production in these cells, there is incomplete expression of the normal natriuretic peptide-induced inhibitory pathway of ACTH secretion at some point distal to the production of cyclic GMP.
...
PMID:Characterization of natriuretic peptide receptor subtypes in the AtT-20 pituitary tumour cell line. 817 9

Natriuretic peptides family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), while receptors for these natriuretic peptides comprise at least three subtypes, i.e. A-type (GC-A), B-type (GC-B) and C-type (clearance). ANP and BNP are cardiac hormones mainly synthesized and secreted by atria and ventricles, respectively, but CNP is a neuropeptide synthesized by brain. Both A- and B-type receptors contain particulate guanylate cyclase within their molecule and mediate biological function via cyclic GMP as a second messenger, whereas C-type receptor is involved in clearance and metabolism of natriuretic peptides. In heart failure, cardiac expression of both ANP and BNP is augmented with increased circulating levels as a cardiac compensatory mechanism. Pathophysiological significance of natriuretic peptides system in heart failure is discussed.
...
PMID:[Natriuretic peptide family]. 839 34

In this study we compared the levels and responsiveness of atrial natriuretic peptide (ANP) receptors in neuronal and astrocyte glial cultures from spontaneously hypertensive (SH) and normotensive (Wistar-Kyoto: WKY) rat brain. Both neuronal and astrocyte glial cultures from the hypothalamus and brain stem of 1-day-old SH and WKY rats display specific high-affinity binding sites for 125I-labeled ANP. The presence of a large population of ANP-C receptors in each type of culture is indicated by the strong competition of 125I-ANP binding by the ring-deleted analogue of ANP [C-ANF-(4-23)]. In neuronal cultures from both strains, C-type natriuretic peptide (CNP-22) was the most effective natriuretic peptide in stimulating guanosine 3',5'-cyclic monophosphate (cGMP) levels, suggesting the presence of ANP-B receptors in these cells. By contrast, ANP was the most effective stimulator of cGMP levels in SH and WKY rat astrocyte glial cultures, suggesting the presence of ANP-A receptors. Here, we have determined that there is a decrease in the maximum binding capacity for 125I-ANP-specific binding in both SH rat neuronal and astrocyte glial cultures compared with their respective control cells. The stimulatory effects of CNP-22 on cGMP levels in SH rat neurons and of ANP on cGMP levels in SH rat astrocytes were significantly reduced compared with their respective WKY rat cultures. Our data suggest that the lower number of ANP receptors in SH rat neuronal and astrocyte glial cultures includes a reduction in the guanylate cyclase-coupled ANP receptors.
...
PMID:ANP receptors in neurons and astrocytes from spontaneously hypertensive rat brain. 839 76

Adipose tissue of the mesenteric territory contains large quantities of natriuretic peptide receptors (NPR) mainly of the NPR-C subtype. Guanylyl cyclase-bound receptors are also present since atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are equally potent in activating this enzyme. While searching for a potential biological role for NP in adipocytes we observed that ANP-mediated generation of cyclic GMP (cGMP) was potentiated when the cells were simultaneously treated with isoproterenol. Indeed, isoproterenol, a beta-adrenergic agonist, and forskolin, an activator of adenylyl cyclase, can both double or triple cGMP production in response to ANF stimulation. There was a direct correlation between the level of cyclic AMP (cAMP) generated and the level of NP-mediated cGMP production suggesting that a cAMP-dependent mechanism may be responsible of this potentiation. To determine whether or not this phenomenon was unique to adipocytes, NPR subtypes were characterized in 4 established cell lines and their cAMP-dependent cGMP behavior examined. A10 and A7r5 smooth muscle cells showed identical ratio of NPR subtypes with about 95% NPR-C and 5% NPR-B. PC12 cells presented 100% NPR-A and NIH 3T3 fibroblasts 50% NPR-C and 50% NPR-B. Regardless of the NPR subtype, forskolin could not potentiate the cGMP generation in these cell lines. These data indicate that the cAMP-dependent potentiation of the NP-mediated cGMP production is unique to adipocytes, appears independent of the guanylyl cyclase-linked NPR subtypes and may be involved in the sensitization of the guanylyl cyclase domain of NPR for a potential biological role of NP in the adipose tissue.
...
PMID:Specific potentiation by cyclic AMP of natriuretic peptide-mediated cyclic GMP production in adipose tissue. 864 24

Blood pressure in the amphibian pulmonary circulation is relatively high because a single ventricle serves both the systemic and pulmonary circulation, creating a high degree of plasma filtration from pulmonary capillaries. Previous studies have shown that lung atrial natriuretic factor (ANF) may have an important physiological function in preventing edema in mammals. In this study, we report the presence of the complete ANF system in the lungs of the toad Bufo paracnemis. Radioimmunoassay of tissue homogenates revealed that toad lung ANF concentration was approximately twice as high (928.5 +/- 83.0 pg mg-1 protein) as that of lung tissue in mammals of a similar size. The amount of ANF was significantly higher in the left than in the right atrium (15.0 +/- 1.2 versus 1.9 +/- 0.8 ng mg-1 protein; N = 4, P < 0.001), while the ventricle contained 488.3 +/- 41.8 pg mg-1 protein. In extracts of both lungs and atria, high-performance liquid chromatography revealed two forms of the peptide; prohormone and a carboxy-terminal peptide of low molecular mass, which is the biologically active form of peptide. The presence of the prohormone suggests that ANF is synthesized in toad lungs and atria. Characterization of toad lung receptors by a competitive binding assay demonstrated three different subtypes of ANF receptors: the guanylyl cyclase (GC) receptors, GC-A and GC-B, as well as clearance (C) receptors. We conclude that the toad Bufo paracnemis has a well-developed complete ANF system in the lung, suggesting that it has a role in toad lung physiology.
...
PMID:Characterization of the atrial natriuretic factor system in lungs of the toad Bufo paracnemis. 869 54

Physiological actions of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are elaborated by membrane-bound natriuretic peptide receptors (NPRs). These receptors possess intracellular guanylate cyclase domains that mobilize cyclic guanosine monophosphate upon binding of peptide. Two distinct NPR subtypes have been described in brain: the NPR-A selectively binds ANP, whereas NPR-B exhibits high affinity for CNP. 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. Significant levels of neuronal NPR-A mRNA expression were observed only in the mitral cell layer of the olfactory bulb, medial habenula, subfornical organ, and area postrema. Expression of NPR-A mRNA was observed in forebrain white matter tracts, suggesting synthesis in glial cells. In contrast, NPR-B mRNA was widely expressed throughout the neuraxis. In the telencephalon, signal was abundant throughout limbic cortex and neocortex, olfactory bulb, hippocampus, and amygdala. Intense NPR-B mRNA hybridization was observed in preoptic-hypothalamic neuroendocrine circuits and in motor nuclei of cranial nerves. Intermediate expression of NPR-B mRNA was observed in brainstem nuclei controlling autonomic function. Labeling for NPR-B but not NPR-A mRNA was observed in pituicytes in the neural lobe of the pituitary and in scattered cells of the anterior pituitary. These results suggest that CNP is the primary biologically active natriuretic peptide in brain. In contrast with NPR-B, NPR-A appears to be expressed largely in restricted cell populations containing high levels of ANP and in circumventricular organs. These data implicate the NPR-A in autoregulation of ANP neurons and central registration of cardiac ANP release.
...
PMID:Localization of natriuretic peptide-activated guanylate cyclase mRNAs in the rat brain. 872 93

The inhibitory effect of atrial natriuretic peptide (ANP) on angiotensin II (AII)-stimulated aldosterone secretion has been previously studied in rat and bovine adrenal zona glomerulosa cells in primary culture. However the understanding of the mode of action of ANP at the molecular level has been hampered by limitations of those primary cell culture systems and by the lack of cell lines from human adrenal cortex. Here we demonstrate the presence of fully functional ANP receptors in the recently characterized AII-responsive adrenocortical carcinoma cell line H295R. Specific saturable binding of 125I-rANP to H295R cell membrane preparations revealed a single class of high affinity binding sites with a density of 20 fmol/mg of protein. The pharmacological profile of this ANP receptor was documented by competitive binding of 125I-rANP with naturally occurring natriuretic peptides. rANP was the most potent with a Kd of 42 pM. pBNP32 was less potent with a Kd of 174 pM. 125I-rANP binding was not competed by pCNP (NPRB-specific ligand) nor by C-ANF (NPRC-specific ligand). Photoaffinity labeling of membrane preparations with 125I-BPA-ANP revealed a single specific protein of molecular weight around 130 kDa. This protein was further identified by immunodetection with a specific antibody directed to the human ANP-specific receptor NPRA. Natriuretic peptides stimulated cGMP production by the receptor-coupled guanylate cyclase with the same specificity. Aldosterone production by AII-stimulated H295R cells was dose-dependently inhibited by rANP with an ED50 of 1.5 nM. In addition, we used this model to test two chimeric analogs of ANP and BNP. pBNP1 and pBNP3 were, respectively, 4- and 2-fold more potent than rANP in competing for 125I-rANP binding with Kd of 10 and 20 pM. pBNP1 was 24-fold more potent in inhibiting AII-stimulated aldosterone production with ED50 of 63 pM. pBNP1 is therefore the most potent natriuretic peptide analog tested. In summary, the human H295R cell line contains NPRA receptors positively coupled to the particulate guanylate cyclase and that antagonize angiotensin II stimulation of aldosterone secretion.
...
PMID:The H295R human adrenocortical cell line contains functional atrial natriuretic peptide receptors that inhibit aldosterone biosynthesis. 873 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---