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:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atrial natriuretic factor (ANF) is degraded by neutral endopeptidase. We hypothesized that neutral endopeptidase inhibition (NEP-I) increases sodium excretion and that this effect would be potentiated in the presence of an isolated increase in intrarenal ANF. In seven anesthetized dogs, ANF was infused into one renal artery to produce pathophysiologic concentrations in the supplemented kidney while the control kidney received physiologic circulating concentrations of ANF. In the control kidney, NEP-I (SQ 28,603) produced significant increases in urine flow, absolute sodium excretion and fractional sodium excretion while glomerular filtration rate (GFR) remained constant. These renal actions of NEP-I were associated with marked increases in urinary excretion of ANF and cyclic GMP consistent with decreased renal degradation and increased biologic activity of ANF. All of these effects were significantly greater in the supplemented kidney. The present study suggests that NEP-I produces natriuresis which appears to be independent of changes in GFR. In addition, while NEP-I mimics the renal action of pathophysiologic levels of ANF, NEP-I also potentiates the natriuretic effects of pathophysiologic concentrations of ANF as observed in congestive heart failure or hypertension.
...
PMID:Neutral endopeptidase inhibition potentiates the renal actions of atrial natriuretic factor. 214 48

Several processes participate in the clearance of atrial natriuretic peptide (ANP) from the circulation, one of which is enzymatic degradation. Endoprotease EC 3.4.24.11 (NEP 24.11), present within the kidney in high concentration, has been shown in vitro to degrade ANP. Phosphoramidon and thiorphan, two potent NEP 24.11 inhibitors, have been shown to prevent the enzymatic degradation of ANP. The purpose of the present study was to determine if phosphoramidon or thiorphan would alter the in vivo time course of the pharmacologic effects of ANP. The magnitude and duration of the ANP-induced increase in urine output and sodium and cyclic GMP excretion were examined with and without either thiorphan or phosphoramidon. Six separate groups of anesthetized rats received either a low, medium, or high infusion rate of thiorphan or phosphoramidon. Renal responses to ANP were potentiated and prolonged during the low phosphoramidon infusion (3 Ki) and the medium thiorphan infusion (150 Ki). At high inhibitor infusion rates in the anesthetized rat, ANP elicited a marked depressor response. In the conscious spontaneously hypertensive rat (SHR), a 15-min intravenous (i.v.) infusion of ANP (1 microgram/kg/min) lowered mean arterial pressure (MAP 23 +/- 6 mm Hg), with an approximately 35-min duration of action. A simultaneous i.v. infusion of phosphoramidon (high dose) produced both a potentiation (33 +/- 3 mm Hg) and a prolongation (greater than 65 min to return to baseline) of the depressor response. These data lend support to the hypothesis that enzymatic breakdown of ANP may play an important role in regulating the actions of atrial natriuretic peptide.
...
PMID:Degradation of atrial natriuretic peptide: pharmacologic effects of protease EC 24.11 inhibition. 247 3

Trophic changes of the exocrine pancreas after in vivo gastrin (G)/CCK treatment are well documented but up to now the study of the mechanisms involved is restricted by the lack of a suitable in vitro model. Nevertheless the in vivo trophic effect induced by gastrin/CCK peptides has been associated with an increase of ornithine decarboxylase (ODC) activity. In the present work, using the AR42J cell line in which CCK receptors and stimulation of amylase release by CCK peptides has already been demonstrated, we investigated the presence of gastrin binding sites and the possible modulation of proliferation by an inhibitor of ODC activity. 125I-BH-G17ns binding is saturable, reversible and specific. Potencies of the different analogues tested are G17ns greater than CCK8 greater than CCK8ns greater than or equal to G6s greater than G/CCK4. Furthermore dBt cGMP, a non-peptide antagonist for CCK receptors, does not compete for gastrin binding. This indicates the existence of a subclass of gastrin binding sites. Difluoromethyl ornithine (DFMO) (1 mM), an irreversible inhibitor of ODC, inhibits cell growth from day 3 up to day 7. This growth inhibition is dose dependent and closely related to an intracellular polyamine modulation. Putrescine and spermidine levels fell under detectable values while spermine levels increased. All these data suggest that this cell line could be a useful in vitro model to study the mechanisms of gastrin induced growth control.
...
PMID:Characterisation of gastrin receptors on a rat pancreatic acinar cell line (AR42J). A possible model for studying gastrin mediated cell growth and proliferation. 312 56

Various agents which are known to affect intracellular levels of cAMP have been assessed for their ability to induce the release of [3H]acetylcholine ([3H]ACH) from a synaptosomal preparation derived from the guinea-pig ileum myenteric plexus. 8-Bromo-cAMP increased the release of [3H]ACh above basal levels. While 8-bromo-cGMP also increased the release, this nucleotide was far less potent than 8-bromo-cAMP. Comparison of the release caused by the cyclic nucleotides to the release induced by the nicotinic agonist dimethylphenylpiperazinium (DMPP) suggested that there is some relationship, as yet undefined, between the 8-bromo-cAMP-induced and the DMPP-induced release, while no relationship was evident between the release induced by 8-bromo-cGMP and that caused by DMPP. The 8-bromo-cAMP-induced release was Ca2+-dependent. Neither adenosine, clonidine, nor oxotremorine (all of which modulate the nicotinically-induced release) affected the 8-bromo-cAMP-induced release. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine stimulated the release of [3H]ACh as did the adenylate cyclase activator forskolin. The forskolin-induced release was not affected by adenosine, clonidine or oxotremorine. The ability of the modulators to block the nicotinically-induced release but not the release caused by the cyclic nucleotides indicates that the modulation of release evoked by nicotinic activity does not occur at a step involving protein phosphorylation.
...
PMID:Stimulation of acetylcholine release from guinea-pig ileal synaptosomes by cyclic nucleotides and forskolin. 620 34

The characteristics of cholecystokinin (CCK) binding to its receptors in a particulate membrane fraction of mouse cerebral cortex were studied by employing biologically active radioiodinated CCK prepared by conjugation with 125I-Bolton-Hunter (125I-BH) reagent. At 24 degrees C binding was rapid, reversible, and linearly related to protein content. Binding was maximal at acidic pH (6.5) and reduced by the presence of monovalent cations. Under physiological conditions (pH 7.4, 118 mM-NaCL, 4.7 mM-KCl) Scatchard plots of CCK binding were linear with a KD value of 1.27 nM and binding capacity of 115 fmol/mg protein. Optimal binding required the presence of both Mg2+ and EGTA, and was inhibited by the addition of micromolar concentrations of Cu2+ (ID50 = 30 microM). The cortical receptor recognized all major forms of CCK, with an order of potency of: cholecystokinin octapeptide (CCK8) greater than CCK greater than cholecystokinin tetrapeptide (CCK4). Desulfated cholecystokinin octapeptide (dCCK8) had a 10-fold lower affinity than CCK8. Dibutyryl cyclic GMP, a potent competitive inhibitor of CCK binding to receptors in pancreas, was not a specific inhibitor of CCK binding to brain receptors. These present results support the concept that CCK may function as a regulatory peptide in brain, and that the cortical CCK receptor is different from the receptors mediating the peripheral action of CCK.
...
PMID:Characterization of receptors for cholecystokinin and related peptides in mouse cerebral cortex. 626 5

The effects of the selective neutral endopeptidase (EC 3.4.24.11, NEP) inhibitor SQ 28,603 on endogenous plasma endothelin (ET) concentration and on the clearance from the circulation of exogenously administered synthetic human ET-1 were examined in Sprague-Dawley rats. Inhibition of NEP by SQ 28,603 (100 mumol/kg intravenously, i.v.) affected neither basal levels of plasma ET nor the circulatory clearance of an i.v. administered bolus dose (3 nmol/kg) of ET-1. ET-1 produced marked, statistically significant increases in plasma atrial natriuretic peptide (ANP) and cyclic GMP concentrations. SQ 28,603 markedly augmented the duration of the increases in plasma concentrations of ANP and cyclic GMP induced by exogenous ET-1. SQ 28,603 alone produced modest but statistically significant increases in plasma ANP and cyclic GMP concentrations that lasted for at least 30 min. These results clearly demonstrate that NEP does not contribute to the in vivo clearance of ET and support the hypothesis that NEP plays an important role in clearance of ANP from the circulation.
...
PMID:Effects of neutral endopeptidase inhibition on the clearance of exogenously administered endothelin in Sprague-Dawley rats. 768 10

Analysis of a developmental mutant in Dictyostelium discoideum which is unable to initiate morphogenesis has shown that a protein kinase of the MAP kinase/ERK family affects relay of the cAMP chemotactic signal and cell differentiation. Strains in which the locus encoding ERK2 is disrupted respond to a pulse of cAMP by synthesizing cGMP normally but show little synthesis of cAMP. Since mutant cells lacking ERK2 contain normal levels of both the cytosolic regulator of adenylyl cyclase (CRAC) and manganese-activatable adenylyl cyclase, it appears that this kinase is important for receptor-mediated activation of adenylyl cyclase.
...
PMID:A MAP kinase necessary for receptor-mediated activation of adenylyl cyclase in Dictyostelium. 784 54

We examined adenosine 5'-triphosphate (ATP), pertussis toxin (PT) and phorbol myristate acetate (PMA), a protein kinase C (PKC) activator, modulation of atrial natriuretic peptide (ANP)-stimulated cell-membrane guanylate cyclase (ANP-s-GC) activity and ANP stimulation of whole-cell cGMP accumulation (ANP-s-cGMP) in an ANP-receptor-transduction cell model, the human renal cell line (SK-NEP-1). Acute and long-term effects of PMA on PKC isotype activity are different: Acute (20-min) PMA activation of PKC inhibits ANP-s-cGMP and ANP-s-GC; whereas, long-term (36-h) PMA treatment inhibits slightly less by only partially down-regulating PKC activity, the type-III PKC isotype being 36-h resistant. Long-term 10(-7)M PMA treatment of cells neither affected membrane basal GC activity nor ANP-s-GC activity but partially inhibited ATP enhancement of ANP-s-GC. This partial inhibition was completely reversed by the PKC inhibitor H7 and a PKC inhibitory antibody but only partially reversed by the antibody to the catalytic domain of PKC type III. The EC50 for ATP and its non-phosphorylating analog ATP gamma S in the presence of acute PMA inhibition of ANP-s-cGMP was similar (approximately 10(-9)). This enhancement of PMA inhibition was two orders of magnitude more sensitive (EC50 10(-7)M) than inhibition of ANP-s-cGMP that we previously reported for acute PMA treatment of whole SK-NEP-1 cells. The three- to four-fold ATP enhancement of cell membrane ANP-s-GC was not blocked by 12-hour preincubation of cells with 150 ng/mL PT but was completely blocked if 2-x-10(-7)M PMA was then added for 20 minutes, indicating that acute activation of PKC by PMA does not require a functional "G-type" protein. Acute PMA inhibition of ANP-s-cGMP was reversed by permeabilizing SK-NEP-1 cells to a specific PKC inhibitory peptide, further confirming that PMA inhibition was mediated through PKC activation. These data demonstrated that ANP-s-GC and ANP-s-cGMP were modified through non-phosphorylating interactions with ATP, by multiple PMA activatable PKC isoforms, and that neither were affected by PT-sensitive guanine-nucleotide-binding (G)-protein(s).
...
PMID:Adenosine 5'-triphosphate, phorbol ester, and pertussis toxin effects on atrial natriuretic peptide stimulation of guanylate cyclase in a human renal cell line. 790 11

Seven new loci, casein alpha-S1 (CSN1S1), casein alpha-S2 (CSN1S2), casein beta (CSN2), the Hardy-Zuckerman 4 feline sarcoma viral (v-kit) oncogene homolog (KIT), albumin (ALB), phosphodiesterase cyclic GMP (rod receptor) beta polypeptide (PDEB), and complement component 1 (IF), were assigned to sheep Chromosome (Chr) 6 by Southern hybridization to a panel of chromosomally characterized sheep x hamster cell hybrids. By isotopic in situ hybridization, CSN2 was regionally localized to sheep Chr (OOV) 6q22-q31, anchoring this syntenic group of markers on to OOV6 and confirming its homology at a molecular and cytological level with cattle Chr 6. The assignment of these loci, from PDEB (located on human Chr 4p16.3) to IF (on HSA4q24-q25), and the observation that interleukin 2 (IL2, on HSA4q26-q27) and tryptophan 2,3-dioxygenase (TDO2, on HSA4q31) are not located on OOV6, is further evidence of the close evolutionary relationship of sheep and cattle and the conserved synteny in these species of this extensive region of human Chr 4. On the basis of this conserved synteny, and the similar G- and Q-banding patterns of this chromosome in cattle and sheep, we propose that this sheep chromosome be numbered as 6, not 4 as recommended by ISCNDA (1990).
...
PMID:Seven loci on human chromosome 4 map onto sheep chromosome 6: a proposal to restore the original nomenclature of this sheep chromosome. 791 55

The cardiovascular consequences of mixed angiotensin converting enzyme and neutral endopeptidase (ACE/NEP) inhibition with alatriopril/alatrioprilat were compared with the consequences of endopeptidase (NEP) inhibition alone with (S)-thiorphan/ecadotril by determining the acute effects of the compounds on hemodynamic, hormonal, and renal parameters in hypertensive transgenic rats harboring an additional mouse renin gene (TGR(mRen2)27). Infusion of alatrioprilat and (S)-thiorphan in anesthetized TGR decreased blood pressure in a dose-dependent manner, but heart rate remained unchanged. The renal excretion of water, sodium, and cGMP also increased dose-dependently, with nearly the same maximal effects after infusion of (S)-thiorphan and alatrioprilat. At the end of infusion, plasma ANP and cGMP were elevated both after (S)-thiorphan and after alatrioprilat, whereas plasma renin activity increased only after alatrioprilat. The ACE inhibition effect was studied in ganglion-blocked rats receiving a continous infusion of angiotensin I. Alatrioprilat decreased the mean blood pressure dose-dependently, but about 30 times higher concentrations were needed to produce the same effects as the ACE inhibitor captopril. At a dose of 30 mg/kg p.o., ecadotril, the orally active prodrug of (S)-thiorphan, decreased the systolic blood pressure in conscious TGR by 22 mmHg for 6 h, whereas alatriopril (100 mg/kg p.o.) also reduced the systolic pressure in these rats with a maximal reduction of 22 mmHg. In addition, ecadotril and alatriopril significantly increased the urinary excretion of sodium. In contrast, ACE inhibition with captopril decreased the excretion of sodium dose-dependently in conscious TGR. In conclusion, combined ACE/NEP inhibition produced a comparable lowering of blood pressure and improvement in renal function as those with NEP inhibition in TGR. Dual ACE/NEP inhibition may therefore be useful in cardiovascular conditions such as hypertension or heart failure.
...
PMID:Cardiorenal consequences of dual angiotensin converting enzyme and neutral endopeptidase 24.11 inhibition in transgenic rats with an extra renin gene. 889 43


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

---