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)

We have evaluated the genes for angiotensin converting enzyme (ACE) and guanylyl cyclase A/atrial natriuretic peptide receptor (GCA) for genetic effects on blood pressure response to high salt diet. In F2 rats derived from Milan normotensive and Dahl salt-hypertension sensitive (S) rats, both ACE and GCA cosegregated with blood pressure, and rats that were homozygous for the S allele at both the ACE and GCA loci had inordinately high blood pressure. In F2 derived from Wistar Kyoto (WKY) and S rats, GCA revealed positive cosegregation with blood pressure, but ACE did not. We conclude that certain alleles at the GCA and ACE loci (or at loci closely linked to them) have a significant genetic impact on blood pressure response to high salt in specific rat strains.
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PMID:Cosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt-sensitive rats. 136 13

Using a bacterial expression system, large amounts of the catalytic core of an atrial natriuretic peptide receptor guanylyl cyclase were produced and purified. After refolding the protein from a buffer containing urea, the enzyme had positively cooperative kinetics with a Hill coefficient, nH = 1.42 +/- 0.08. Size exclusion chromatography and denaturing polyacrylamide gel electrophoresis demonstrated that the enzyme is composed of homodimers with interacting catalytic sites.
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PMID:Overexpression of dimeric guanylyl cyclase cores of an atrial natriuretic peptide receptor. 168 32

A polypeptide containing the catalytic domain of an atrial natriuretic peptide receptor guanylate cyclase has been produced using a bacterial expression system. A carboxyl fragment of the membrane form of guanylate cyclase from rat brain, which contains a region homologous to soluble guanylate and adenylate cyclases, was expressed in Escherichia coli with a double plasmid system that encodes T7 RNA polymerase (Tabor, S., and Richardson, C.C. (1985) Proc. Natl. Acad. Sci. U. S. A. 82, 1074-1078). Application of this expression system permitted exclusive radiolabeling of the cloned gene product, thereby providing a means to evaluate the level of expression and stability of encoded proteins. Fusion proteins were formed with the T7 bacteriophage gene 10 product and the 293 carboxyl-terminal residues of guanylate cyclase and two deletional mutants encoding 105 and 69 residues. Extracts prepared from bacteria expressing the carboxyl region, but not those expressing further deletions in this region, had substantial guanylate cyclase activity. There was no associated adenylate cyclase activity, suggesting that the catalytic domain retained its enzymatic specificity. These results provide direct evidence that the carboxyl portion of the membrane form of guanylate cyclase contains a catalytic domain. Homologous regions of the soluble form of guanylate cyclase and adenylate cyclase are likely to have enzymatic properties.
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PMID:The carboxyl region contains the catalytic domain of the membrane form of guanylate cyclase. 197 86

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. The gene spans about 17.5 kilobases and includes 22 exons and 21 introns. All of the exon-intron junction sequences coincide with the GT/AG consensus. GC-A consists of at least the following four distinguishable domains: extracellular ligand binding, transmembrane, kinase-like, and cyclase catalytic. Exon 7 encodes the putative transmembrane domain. The kinase-like and catalytic domains are encoded by exons 8-15 and 16-22, respectively. The 5' end of the transcript, estimated by primer extension and S1 mapping, is 370 nucleotides upstream of the methionine initiation codon. The initiator sequence (-3 to +5) of CACACTCC has two mismatches when compared with a consensus initiator sequence of CTCANTCT. The 5'-flanking region contains three potential Sp1-binding sites and an inverted CCAAT box, but no apparent TATA box. Three different and short interspersed, repetitive sequences are found within intervening sequences and within the 5'- and 3'-flanking regions of the gene (five rat identifier, two rat type 2 Alu equivalent, and seven Alu-like sequences). They fall between the four major domains suggestive that these may be sites for frequent recombination events. This first reported structure of a gene for a member of this new enzyme/receptor family should facilitate the search for new family members, as well as allow studies to progress on the mechanisms by which the gene is regulated.
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PMID:The primary structure of the rat guanylyl cyclase A/atrial natriuretic peptide receptor gene. 197 22

A cDNA clone for the membrane form of guanylate cyclase has been isolated from the testis of the sea urchin Strongylocentrotus purpuratus. An open reading frame predicts a protein of 1125 amino acids including an apparent signal peptide of 21 residues; a single transmembrane domain of 25 amino acids divided the mature protein into an amino-terminal, extracellular domain of 485 amino acids and a carboxyl domain of 594 intracellular amino acids. Three potential Asn-linked glycosylation sites were present in the proposed extracellular domain. The deduced protein sequence was homologous to the protein kinase family and contained limited but significant regions of identity with a low molecular weight atrial natriuretic peptide receptor. The carboxyl region (202 amino acids) was 42% identical with a subunit of the cytoplasmic form of guanylate cyclase recently cloned from bovine lung (Koesling, D., Herz, J., Gausepohl, H., Niroomand, F., Hinsch, K.-D., Mulsch, A., Bohme, E., Schultz, G., and Frank, R. (1988) FEBS Lett. 239, 29-34). Therefore, the membrane form of guanylate cyclase is a member of an apparently large family of proteins that includes the low molecular weight atrial natriuretic peptide receptor, the soluble form of guanylate cyclase and protein kinases.
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PMID:The membrane form of guanylate cyclase. Homology with a subunit of the cytoplasmic form of the enzyme. 256 49

We have compared the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) on the accumulation of cyclic GMP (cGMP) in secondary cultures of rat astrocytes. The order of potency of these peptides was CNP > ANP > BNP, which would be compatible with a predominance of guanylate cyclase B (GC-B)- versus guanylate cyclase A (GC-A)-type receptors in these cells. Accordingly, we found by northern blot analysis that the mRNA transcripts of GC-B were much more abundant in astrocytes than the transcripts of GC-A. In addition, astrocytes from diencephalon accumulated two times more cGMP in response to CNP than astrocytes from cortex. Binding experiments with 125I-labeled ANP or [Tyro]-CNP established that these ligands recognized only clearance-type receptors on astrocytes. However, the number of binding sites was approximately 100 times higher in astrocytes from cortex than in astrocytes from diencephalon and thus was inversely correlated to the amplitude of the cGMP response in the same cells. We found no further evidence for differences in the levels of GC-B receptors in astrocytes from the two regions because (a) the abundance of GC-B mRNA was similar and (b) there was no difference in particulate guanylate cyclase activity in astrocytes from each region. In addition, occupancy of clearance receptors with C-ANP4-23 did not affect the accumulation of cGMP in response to CNP; this makes it unlikely that the differences in cGMP responsiveness can be accounted for by binding and sequestration of CNP to the clearance receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of C-type natriuretic peptide on rat astrocytes: regional differences and characterization of receptors. 790 48

1. Guanylate cyclase plays an important role in the visual cycle. Here we report the mRNA expression for the atrial natriuretic peptide receptor type A form of guanylate cyclase (ANPRA) in human retina. 2. Polymerase chain reaction using two sets of primers on the cDNAs reverse-transcribed from human retinal poly(A)+ RNA amplified two products under two different reaction conditions. The primers used in the reaction were designed from the reported sequence of human placental ANPRA cDNA. 3. Sequencing of the amplified products showed 100% sequence homology to the human placental ANPRA gene. Northern blot analysis indicated the presence of a 4.4-kb ANPRA mRNA in human retina, similar to that present in human brain.
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PMID:Expression of mRNA for atrial natriuretic peptide receptor guanylate cyclase (ANPRA) in human retina. 795 58

The effects of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) on renal medullary thick ascending limb (mTAL) have not been fully understood. The aim of this study is to examine the second-messenger responses of rat mTAL to ANF, BNP, and CNP. Characterizations of the ANF, BNP, and CNP receptors in mTAL were also performed by radioligand studies. Results showed that ANF and BNP were both capable of eliciting cyclic guanosine monophosphate (cGMP) responses in mTAL. Conversely, no cGMP response was observed upon stimulation by CNP in mTAL. The presence of ANF receptors was demonstrated by radioligand studies. One receptor site was found, and the Kd and maximum binding capacity were 4.0 +/- 0.45 nmol/L and 277.8 +/- 47.7 fmol/mg protein, respectively. BNP receptors were also found in mTAL, and ANF and BNP were sharing the same receptor. On the contrary, no CNP receptor could be shown by radioligand studies. These results suggest that guanylyl cyclase-coupled receptors (atrial natriuretic peptide receptor-A [ANPR-A]) specific for ANF and BNP are present in rat mTAL, while those for CNP (ANPR-B) are absent. ANF and BNP but not CNP act on mTAL to control water excretion.
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PMID:Cyclic guanosine monophosphate responses to atrial natriuretic factor, brain natriuretic peptide, but not C-type natriuretic peptide, and the characterization of their receptors in rat medullary thick ascending limb. 799 Jul 7

Receptor-specific variants of atrial natriuretic peptide (ANP) were selected from libraries of filamentous phage particles that displayed single copies of random ANP mutants fused to gene III protein. These ANP variants were differentially selected by binding to immobilized natriuretic peptide receptor A (NPR-A) over competing receptor C (NPR-C) in solution. This method also selected ANP variants with improved secretion expression in Escherichia coli. Several of the identified mutations were combined to produce an efficiently expressed ANP analog that was as potent as wild-type ANP in stimulating NPR-A guanylyl cyclase activity but resistant to inactivation mediated by NPR-C. Such NPR-A-selective analogs should be useful for correlating the various activities of ANP to the relevant receptor and may also be more potent therapeutics in the targeting of NPR-A.
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PMID:Production of an atrial natriuretic peptide variant that is specific for type A receptor. 801 51

1. The effects of nitric oxide-donating compounds and atrial natriuretic peptide on cyclic GMP accumulation and mechanical tone were compared with the effects of isoprenaline in bovine tracheal smooth muscle. 2. Sodium nitroprusside, glyceryl trinitrate, S-nitroso-N-acetylpenicillamine (SNAP), atrial natriuretic peptide and isoprenaline each caused concentration-dependent inhibitions of histamine-maintained tone (EC50 values 320 +/- 80, 150 +/- 45, 14,000 +/- 4,000, 2.8 +/- 0.8 and 6.6 +/- 4.3 nM respectively). 3. When compared with their effects on histamine-induced tone, sodium nitroprusside was equally potent and effective in causing relaxation of methacholine-supported tone (EC50 290 +/- 90 nM) while isoprenaline was as effective, but less potent (EC50 30 +/- 7 nM). SNAP was more potent and equi-effective as a relaxant of methacholine-supported tone (EC50 340 +/- 140 nM). At the maximum concentrations of glyceryl trinitrate and atrial natriuretic peptide tested against methacholine-supported tone, relaxations of 52% and 14% of the isoprenaline maximum were seen. 4. Sodium nitroprusside, glyceryl trinitrate and atrial natriuretic peptide each induced concentration-dependent increases in cyclic GMP accumulation. The time-courses of accumulation correlated closely with the relaxant actions of these compounds. 5. Pretreatment of tracheal smooth muscle with sodium nitroprusside or SNAP caused a rightward shift of the concentration-effect curve for histamine while reducing the maximum response. 6. LY 83583, a putative guanylyl cyclase inhibitor, caused a concentration-dependent reduction in basal cyclic GMP accumulation in tracheal smooth muscle and inhibited the effects of sodium nitroprusside on cyclic GMP accumulation. 7. LY 83583 also inhibited the relaxation of histamine-supported tone by glyceryl trinitrate, sodium nitroprusside, SNAP and atrial natriuretic peptide, and also sodium nitroprusside- and SNAP-induced relaxation of methacholine-supported tone. However, it had no significant effect on glyceryl trinitrate-induced relaxation of methacholine-supported tone. 8. It is concluded that the relaxant actions of sodium nitroprusside, glyceryl trinitrate, SNAP and atrial natriuretic peptide follow as a result of their ability to activate either soluble or particulate guanylyl cyclase leading to cyclic GMP accumulation. Although there does not seem to be any functional difference in the relaxant response to cyclic GMP generated by the particulate as opposed to soluble form(s) of guanylyl cyclase, atrial natriuretic peptide receptor/guanylyl cyclase activation was much less effective in causing relaxation of methacholine-supported tone when compared to activators of soluble guanylyl cyclase.
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PMID:Comparative effects of activation of soluble and particulate guanylyl cyclase on cyclic GMP elevation and relaxation of bovine tracheal smooth muscle. 854 69


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