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)

All components of the natriuretic peptide (NP) system have been found in the ovary. The purpose of this study was to determine the hormonal regulation of the NP system during follicular growth and ovulation induced by gonadotropins eCG and hCG. Ovarian membrane binding, before and after treatment, revealed the presence of guanylyl cyclase-type receptors exclusively. Equine CG treatment increased Bmax from 225 +/- 50 fmol/mg protein in control animals to 354 +/- 51 fmol/mg protein, and additional hCG treatment increased it further to 492 +/- 130 fmol/mg protein (p < 0.05), without changing receptor affinity. The increased binding was consistent with increased ability of atrial natriuretic peptide (ANP) to activate guanylyl cyclase in the ovarian cells obtained from hormone-treated animals. In confirmation, autoradiography of 125I-tyroCNP and 125I-ANP binding to the rat ovary showed that both guanylyl cyclase GC-A and GC-B receptor subtypes are localized to the granulosa cells of antral follicles. Quantitative analysis of GC-A and GC-B receptors by reverse transcription-polymerase chain reaction showed that the expression level of both receptors started to increase at 2 h and reached maximal levels at 6 h following eCG treatment. Increased levels of GC-B mRNA were also observed 12 h after eCG injection. At 24 and 48 h the receptor levels were below basal. Stimulation of NP receptors by eCG was paralleled by activation of both ovarian ANP and C-type natriuretic peptide (CNP) gene expression. ANP mRNA increased as early as 1 h after eCG injection and remained elevated up to 6 h. CNP mRNA increased at 2 h after eCG injection, peaked (5-fold) at 6 h, and remained elevated 48 h later, a stage at which follicular maturation continues. Incubation of ovaries with ANP significantly decreased eCG-induced estradiol level, indicating the functionality of the ovarian NP system. These results implicate the NP system in the induction and maintenance of fluid balance in the rapidly developing ovarian follicle.
...
PMID:Hormonal regulation of natriuretic peptide system during induced ovarian follicular development in the rat. 1037 45

Natriuretic peptides (NPs), mainly produced in heart [atrial (ANP) and B-type (BNP)], brain (CNP), and kidney (urodilatin), decrease blood pressure and increase salt excretion. These functions are mediated by natriuretic peptide receptors A and B (NPRA and NPRB) having cytoplasmic guanylyl cyclase domains that are stimulated when the receptors bind ligand. A more abundantly expressed receptor (NPRC or C-type) has a short cytoplasmic domain without guanylyl cyclase activity. NPRC is thought to act as a clearance receptor, although it may have additional functions. To test how NPRC affects the cardiovascular and renal systems, we inactivated its gene (Npr3) in mice by homologous recombination. The half life of [125I]ANP in the circulation of homozygotes lacking NPRC is two-thirds longer than in the wild type, although plasma levels of ANP and BNP in heterozygotes and homozygotes are close to the wild type. Heterozygotes and homozygotes have a progressively reduced ability to concentrate urine, exhibit mild diuresis, and tend to be blood volume depleted. Blood pressure in the homozygotes is 8 mmHg (1 mmHg = 133 Pa) below normal. These results are consistent with the sole cardiovascular/renal function of NPRC being to clear natriuretic peptides, thereby modulating local effects of the natriuretic peptide system. Unexpectedly, Npr3 -/- homozygotes have skeletal deformities associated with a considerable increase in bone turnover. The phenotype is consistent with the bone function of NPRC being to clear locally synthesized CNP and modulate its effects. We conclude that NPRC modulates the availability of the natriuretic peptides at their target organs, thereby allowing the activity of the natriuretic peptide system to be tailored to specific local needs.
...
PMID:The natriuretic peptide clearance receptor locally modulates the physiological effects of the natriuretic peptide system. 1037 27

Histochemical reaction of NADPH-diaphorase (NOS-NADPH-d) was used to identify NO synthesis. A 30-min 0.1 microg microg/kg/min ANP infusion led to about a 10% and 35% increase in small and large intestine enterocytes stain respectively. This increase was abolished by a bolus of 1 mg/kg L-NAME before ANP infusion in small intestine, and partially abolished it in colon. Incubation of small and large intestine with 0.5 microM ANP increased stain at about 20%. In both tissues the preincubation with 0.1 mM L-NAME abolished the ANP effect. Incubation with 0.1 mM 8-Br-cGMP enhanced staining about 70% and 30% in small and large intestine respectively. Our results show that ANP enhances NOS-NADPH-d activity, suggesting that ANP stimulates NO synthase in enterocytes by L-arginine-NO pathway. 8-Br-cGMP mimicked the effect of ANP described above. Therefore, the guanylate cyclase-coupled natriuretic receptors, NPR-A and NPR-B, probably mediate this ANP effect.
...
PMID:Atrial natriuretic peptide effect on NADPH-diaphorase in rat intestinal tract. 1046 14

The natriuretic peptide (NP) system consists of three types of hormones [atrial NP (ANP), brain or B-type NP (BNP), and C-type NP (CNP)] and three types of receptors [NP receptor (R)-A, NPR-B, and NPR-C]. ANP and BNP are circulating hormones secreted from the heart, whereas CNP is basically a neuropeptide. NPR-A and NPR-B are membrane-bound guanylyl cyclases, whereas NPR-C is assumed to function as a clearance-type receptor. ANP, BNP, and CNP occur commonly in all tetrapods, but ventricular NP replaces BNP in teleost fish. In elasmobranchs, only CNP is found, even in the heart, suggesting that CNP is an ancestral form. A new guanylyl cyclase-uncoupled receptor named NPR-D has been identified in the eel in addition to NPR-A, -B, and -C. The NP system plays pivotal roles in cardiovascular and body fluid homeostasis. ANP is secreted in response to an increase in blood volume and acts on various organs to decrease both water and Na+, resulting in restoration of blood volume. In the eel, however, ANP is secreted in response to an increase in plasma osmolality and decreases Na+ specifically, thereby promoting seawater adaptation. Therefore, it seems that the family of NPs were originally Na(+)-extruding hormones in fishes; however, they evolved to be volume-depleting hormones promoting the excretion of both Na+ and water in tetrapods in which both are always regulated in the same direction. Vertebrates expanded their habitats from fresh water to the sea or to land during evolution. The structure and function of osmoregulatory hormones have also undergone evolution during this ecological evolution. Thus, a comparative approach to the study of the NP family affords new insights into the essential function of this osmoregulatory hormone.
...
PMID:Structural and functional evolution of the natriuretic peptide system in vertebrates. 1049 24

The natriuretic peptides are a group of structurally similar but genetically distinct peptides that have diverse actions in cardiovascular, renal, and endocrine homeostasis. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are of myocardial cell origin and C-type natriuretic peptide (CNP) is of endothelial origin. ANP and BNP bind to the natriuretic peptide-A receptor (NPR-A), which, via 3',5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodilation, renin inhibition, antimitogenesis, and lusitropic properties. CNP lacks natriuretic actions but possesses vasodilating and growth-inhibiting actions via the guanylyl cyclase-linked natriuretic peptide-B receptor (NPR-B). All three peptides are cleared by the natriuretic peptide-C receptor (NPR-C) and are degraded by the ectoenzyme neutral endopeptidase 24.11 (NEP), both of which are widely expressed in the kidneys, lungs, and the vascular wall. Congestive heart failure (CHF) represents a pathological state in which the activation of the natriuretic peptides exceeds those of all other states. In this brief review, we will attempt to provide an update on important issues regarding natriuretic peptides in CHF, with a focus on their functional importance as a beneficial humoral response in asymptomatic left ventricular dysfunction (LVD), the mechanisms of natriuretic peptide hyporesponsiveness in severe heart failure, the diagnostic and prognostic significance of the natriuretic peptides in CHF, and the therapeutic potential of the natriuretic peptides in this multiorgan syndrome.
...
PMID:The natriuretic peptides in heart failure: diagnostic and therapeutic potentials. 1051 61

C-type natriuretic peptide (CNP), the third member of the atrial natriuretic peptide family, acts via guanylyl cyclase containing GC-B receptors to stimulate cyclic guanosine 3',5' monophosphate (cGMP) accumulation in the gonadotrope-derived alphaT3-1 cell line and rat pituitary cells. This effect is inhibited by concomitant activation of the phospholipase C (PLC)-coupled gonadotrophin hormone-releasing hormone (GnRH) receptors in these cells. Since GnRH stimulates gonadotrophin secretion from gonadotropes by increasing the cytosolic Ca2+ concentration ([Ca2+]i) and natriuretic peptides have been found to influence PLC/Ca2+ signalling in other systems, we have investigated whether CNP can alter basal or GnRH-stimulated changes in [Ca2+]i in alphaT3-1 cells. In Ca 2+-containing medium, 10(-7) M CNP modestly, but significantly increased [Ca2+]i over several min, but subsequently inhibited the elevation of [Ca2+]i in response to 10(-7) M GnRH in both Ca2+-containing and Ca2+-free medium. This inhibitory effect was mimicked by 10(-6) M 8-Br-cGMP, but not by ANP, indicating mediation by cyclic GMP and the CNP-specific GC-B receptor. However, basal and GnRH-stimulated inositol (1,4,5) trisphosphate (Ins(1,4,5)P3) generation were not measurably affected by CNP, and CNP failed to affect thapsigargin-induced capacitative Ca2+ entry. Thus, it appears that the cross-talk between CNP and GnRH in these cells is reciprocal in that GnRH modulates CNP effects on cGMP generation, whereas, CNP modulates GnRH effects on Ca2+ mobilisation.
...
PMID:C-type natriuretic peptide (CNP) effects on intracellular calcium [Ca2+]i in mouse gonadotrope-derived alphaT3-1 cell line. 1053 7

The binding of atrial natriuretic peptide and C-type natriuretic peptide to the guanylyl cyclase-linked natriuretic peptide receptors A and B (NPR-A and NPR-B), respectively, results in decreases in extracellular volume, vascular tension and cell proliferation. Both NPR-A and NPR-B are extensively phosphorylated in resting cells and receptor dephosphorylation is correlated with ligand-induced homologous desensitization. To understand the role of phosphorylation in the regulation of these receptors, we identified the in vivo phosphorylation sites of NPR-A and NPR-B and found that the phosphorylation of multiple sites within their kinase homology domains is absolutely required for their activation. In this review, we give a detailed description of the phosphopeptide mapping techniques that were used to identify and characterize these sites and discuss the potential pitfalls that are associated with them.
...
PMID:Identification and characterization of the phosphorylation sites of the guanylyl cyclase-linked natriuretic peptide receptors A and B. 1058 Nov 50

Guanosine 3',5'-cyclic monophosphate (cGMP) has been recently reported to be involved in bone formation. ATDC5 cells were used to investigate cGMP metabolism during chondrogenic differentiation. Natriuretic peptide receptor (NPR)-A and NPR-B coupled with guanylate cyclase (GC) mediate biological functions of NPs, whereas NPR-C uncoupled with GC is thought to be the clearance receptor for NPs. The amounts of NPR-A, NPR-B, and CNP transcripts were increased but the amount of NPR-C transcripts was decreased in association with the chondrogenic differentiation of ATDC5 cells. CNP, a specific ligand for NPR-B lets ATDC5 cells accumulate great amounts of cGMP, revealing NPR-B as a dominant biological receptor through differentiation. cGMP hydrolytic activities of PDE1 and PDE5 existed in ATDC5 cells, and the activity of PDE1, which is stimulated by Ca(2+) and calmodulin (CaM) was major of them. Total cGMP hydrolytic activities as well as the amounts of PDE1 and PDE5 transcripts were enhanced during chondrogenic differentiation. Therefore, cGMP production and hydrolysis, cGMP metabolism was considered to be activated in association with chondrogenic differentiation of ATDC5 cells. These observations may lead to a better understanding of cGMP in the chondrocytes where bone formation occurs.
...
PMID:Alteration of cGMP metabolism during chondrogenic differentiation of chondroprogenitor-like EC cells, ATDC5. 1059 Mar 11

Natriuretic peptide (NP) receptors (NPRs) located at the endocardial endothelium are suggested to be involved in regulating myocardial contractility. However, the characteristics and modulation of NPRs in relation to cardiac failure are not well defined. This study examined the properties of NPRs in ventricular endocardium using quantitative receptor autoradiography, RT-PCR, Southern blot analysis, and activation of particulate guanylyl cyclase (GC) by NPs. In control rats, specific 125I-labeled rat atrial NP (rANP)(1-28) binding sites were localized in right (RV) and left ventricular (LV) endocardium. Binding affinities of 125I-rANP(1-28) were remarkably higher in RV than LV endocardium. Radioligand binding at these sites was mostly inhibited by des[Gln18,Ser19,Gly20,Leu21, Gly22]ANP(4-23), a specific NP clearance receptor ligand. mRNAs for all three recognized NPRs were detected in endocardial cells by RT-PCR and confirmed by Southern blot analysis. Production of cGMP by particulate GC in endocardial cell membranes was stimulated by NPs with a rank order of potency of C-type NP(1-22) >> brain NP (BNP)(1-26) > ANP(1-28). We also examined the modulation of these NPRs during cardiac hypertrophy induced by monocrotaline (MCT). In MCT-treated rats with pulmonary hypertension, specific (125)I-rANP(1-28) binding to hypertrophied RV endocardium almost disappeared and cGMP production by NPs was significantly decreased. In rats with pulmonary hypertension, plasma levels of ANP and BNP were increased by fivefold compared with controls. 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. Downregulation of NPRs may be associated with an increment of endogenous NP production caused by mechanical overload in hypertrophied ventricle.
...
PMID:Modulation of endocardial natriuretic peptide receptors in right ventricular hypertrophy. 1060 Aug 47

Natriuretic peptides form a family of structurally related peptides known to regulate salt and water homeostasis and to cause vasodilation. Synthesis of atrial (ANP), brain (BNP), and C-type (CNP) natriuretic peptides occurs mainly in the heart and brain and has been identified recently in the female reproductive tract. The expression of ANP and CNP as well as their cognate guanylyl cyclase receptors (NPR-A and NPR-B, respectively) have been detected in the rat ovary. We have shown previously that the expression of the natriuretic peptides and their receptors in the rat ovary appears to be modulated by the estrous cycle. In the present study we have evaluated the expression of the natriuretic peptide system (peptide and receptor) in ovarian cells (granulosa and thecal-interstitial cells) obtained from immature female rats treated with either diethylstilbestrol (DES), an estrogen analog, or equine CG (eCG), a gonadotropin that possesses both LH and FSH activity. Using a whole cell RRA, we found that CNP binding was increased by 2-fold in granulosa cells taken from animals treated with either DES or eCG. 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. The activity of the receptors was assessed by ligand-dependent stimulation of cGMP release. CNP, but not ANP, stimulated the release of cGMP from granulosa cells obtained from DES-treated, but not from eCG-treated, animals. The relative levels of CNP mRNA in granulosa cells were unaltered by either DES or eCG treatment. In contrast, CNP mRNA levels were increased more than 2-fold, but only in theca-interstitial from the eCG-treated animals. Our results indicate that CNP and NPR-B are expressed in the ovary, and their expression is responsive to hormonal treatments. Furthermore, expression of these components of the natriuretic peptide system appears to be compartmentalized, with CNP being derived from the extrafollicular compartment and acting, through NPR-B, on the granulosa cells.
...
PMID:B-type natriuretic peptide receptor expression and activity are hormonally regulated in rat ovarian cells. 1065 Sep 35


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

---