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

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

Recent evidence suggests that the newly described natriuretic peptide, C-type natriuretic peptide (CNP), may be the circulating form of natriuretic peptide in the shark. In the shark CNP has a major site of action in the rectal gland, which augments chloride secretion in response to stimulation by volume loading or CNP infusion. We therefore examined the shark rectal gland for natriuretic peptide receptors and determined the presence of guanylate cyclase-linked receptors and non-guanylate cyclase-linked receptors for CNP in this tissue. CNP binds with uniform high affinity (dissociation constant of 78 +/- 11 pM) to receptors of high density (receptor density of 61 +/- 0.7 fmol/mg protein) in plasma membranes prepared from the rectal gland. By use of rat atrial natriuretic peptide (rANP) as a competing ligand, two classes of receptors become apparent in this population, both of which have similar affinity for CNP, but different affinities for rANP. The low-molecular-weight natriuretic peptide receptor-specific peptide, des-[Gln116,Ser117,Gly118, Leu119,Gly120]rANP-(102-121), binds to 50% of the receptors in the rectal gland, but fails to bind to the remaining 50% even at micromolar concentrations. Porcine brain natriuretic peptide (pBNP) binds with uniformly diminished affinity to all receptors, whereas the unrelated peptide, porcine vasoactive intestinal peptide, does not bind these receptors. The importance of the integrity of the ring structure of CNP is underlined by the significant loss of affinity when the peptide ring is opened.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:C-type natriuretic peptide receptors and signaling in rectal gland of Squalus acanthias. 809 72

The natriuretic peptide receptor type A (NPR-A) is a receptor-guanylyl cyclase whose cytoplasmic enzymatic activity is stimulated by atrial natriuretic peptide binding to the extracellular domain. NPR-A expressed in COS cells is heterogeneously glycosylated, and the more highly glycosylated protein is also phosphorylated. Upon hormone binding, dephosphorylation occurs from both serine and threonine residues, probably within the kinase homology domain of NPR-A, and may be involved with receptor desensitization. Using site-specific mutations in the kinase homology domain of NPR-A, we have identified several residues that are important for regulating the guanylyl cyclase activity of NPR-A. Some of these amino acids are probably essential for maintaining the proper tertiary structure of the intracellular domain, and others may form loops that allow for binding of ATP, which is required for proper enzymatic activity. The site-specific mutants which have greatly reduced enzymatic activity are not phosphorylated and are incompletely glycosylated. These results suggest a correlation between phosphorylation and complete glycosylation of NPR-A and that both are required for hormone-induced enzymatic activity.
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PMID:Proper glycosylation and phosphorylation of the type A natriuretic peptide receptor are required for hormone-stimulated guanylyl cyclase activity. 809

Two classes of high-affinity binding sites for atrial natriuretic peptide (ANP) were identified in a microsomal fraction from human placental artery using radioligand binding methods and des[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4-2 3) (C-ANP), a partially ring-deleted analogue of ANP, consistent with the presence of ANP-A and ANP-C receptor subtypes in this tissue [dissociation equilibrium constant (Kd) 58 pM, maximum binding capacity (Bmax) 14 fmol/mg membrane protein, and Kd 82 pM, Bmax 28 fmol/mg, respectively]. ANP activated a guanylate cyclase present in a particulate fraction from placental vascular tissue with half-maximal response at 104 pM and a maximal rate of guanosine 3',5'-cyclic monophosphate production of 62 pmol.min-1 x mg protein-1. Human brain natriuretic peptide was 10-fold less effective than ANP in stimulating guanylate cyclase activity, indicating the absence of the ANP-B receptor subtype. C-ANP had no effect on basal or ANP-stimulated enzyme activity. This report demonstrates the presence of functional (guanylate cyclase-coupled) receptors for ANP in the human fetoplacental vasculature, suggesting that ANP may have a role in the regulation of fetoplacental hemodynamics.
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PMID:Characterization of atrial natriuretic peptide receptors in human fetoplacental vasculature. 809 22

HS-142-1, a novel non-peptide antagonist for natriuretic peptides, exerts antagonistic actions almost equally on two similar guanylate cyclase-linked natriuretic peptide receptors (GC-A and GC-B), but has little or no effect on the binding of natriuretic peptides to a membrane protein, the so-called "clearance receptor", which binds all natriuretic peptides. The third mammalian form of membrane bound guanylate cyclases (GC-C) was identified not as a natriuretic peptide receptor, but as a receptor for heat-stable enterotoxins (STa). In this study, we examined effects of HS-142-1 on GC-C (STaR) in T84 cells and showed that HS-142-1 exerts neither agonistic nor antagonistic activity for GC-C, indicating that HS-142-1 is not a common antagonist for a family of membrane bound guanylate cyclase receptors, but a specific antagonist for the guanylate cyclase-linked natriuretic peptide receptors.
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PMID:HS-142-1, a novel antagonist for natriuretic peptides, has no effect on the third member of membrane bound guanylate cyclases (GC-C) in T84 cells. 809 19

The natriuretic peptide family of proteins acts through two distinct classes of receptors that signal through entirely different mechanisms. The elucidation of the structure of the guanylate cyclase-containing receptor proteins has provided a better understanding of the mechanisms by which the natriuretic peptides regulate diverse functions of salt and water balance, in conjunction with other vasoactive peptides. A second receptor class was named for the originally described function of this protein to clear the natriuretic peptides from plasma. The mechanism of signaling for the natriuretic peptide clearance receptor is not firmly established. All known members of the natriuretic peptide family bind to, and can theoretically act through, the clearance receptor. This review summarizes the known features of the natriuretic peptide clearance receptor, a protein that contains extracellular and transmembrane domains and a short cytoplasmic segment. Recent studies have pointed to new and potentially important functions for this protein in mediating the actions of the natriuretic peptides.
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PMID:Natriuretic peptide C-receptor: more than a clearance receptor. 809 74

We studied the cytochemical localization of particulate guanylate cyclase (GC) in rat adrenal gland after stimulation with porcine brain natriuretic peptide (pBNP) by electron microscopy. In the adrenal cortex, GC activity, as demonstrated by the presence of reaction product, was prevalently localized to the zona glomerulosa and zona fasciculata, while the zona reticularis showed little GC reaction product. In the adrenal medulla, GC reaction product was present only in adrenalin-containing cells. All GC positivity was associated with intracellular membranes. No GC reaction product was detected in specimens incubated in media devoid of pBNP. In parallel samples incubated in the presence of rat atrial natriuretic factor (rANF), the distribution of rANF-stimulated GC activity was similar to that of pBNP-stimulated GC activity.
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PMID:Ultracytochemical localization of particulate guanylate cyclase in rat adrenal gland exposed to stimulation by porcine brain natriuretic peptide. 810 May 60

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.
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PMID:[Molecular biology and pharmacology of natriuretic peptide system]. 810 May 90

Recent molecular cloning reports show that there are at least three membrane guanylate cyclases in vertebrate retina: (1) atrial natriuretic factor receptor guanylate cyclase (ANF-RGC), (2) C-type natriuretic peptide receptor guanylate cyclase (CNP-RGC), and (3) "retinal guanylate cyclase" (RetGC). The specific cellular localization of the first two cyclases is unknown, but RetGC is apparently localized in photoreceptor cells, suggesting that it participates in visual transduction. With the overall objective of identifying the guanylate cyclase that is linked to phototransduction, we compared the structural and regulatory properties of the biochemically characterized 112 kDa bovine rod outer segment membrane guanylate cyclase (ROS-GC) with those of RetGC, ANF-RGC and CNP-RGC. The N-terminal and two internal peptide sequences of purified ROS-GC had about 90% similarity with the corresponding sequences of the RetGC; the sequence identity with natriuretic peptide receptor cyclases was about 30%. A 19 amino acid long sequence from a tryptic peptide of ROS-GC had no corresponding sequence in the other three cyclases. ROS-GC was inhibited by ATP but ANF-RGC and CNP-RGC were activated by ATP in the presence of the respective peptide hormones. These results suggest that ROS-GC represents a new subtype of the membrane guanylate cyclase family that is structurally and biochemically distinct from the other retinal cyclases.
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PMID:Structural and biochemical identity of retinal rod outer segment membrane guanylate cyclase. 810 54

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.
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PMID:Different ATP effects on natriuretic peptide receptor subtypes in LLC-PK1 and NIH-3T3 cells. 810 67

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.
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PMID:Characterization of natriuretic peptide receptor subtypes in the AtT-20 pituitary tumour cell line. 817 9


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