Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In the anaesthetized, ganglion-blocked rat, intravenous boluses of endothelin-1, endothelin-2 and endothelin-3 induced a transient hypotensive effect followed by a potent long lasting pressor response (ED50 mmHg: 0.72 +/- 0.05, 1.8 +/- 0.2 and 2.7 +/- 0.3 nmol kg-1, respectively). The maximal effect for the three peptides was of a similar order of magnitude (delta MAP: 84 to 89 mmHg). Neither of these effects was influenced by phosphoramidon or thiorphan (10 mg kg-1, i.v.). 2. Intravenously administered big-endothelin-1 and -2 induced a transient (1-2 min) hypotension followed by a potent long lasting (> 25 min) vasopressor effect (ED50 mmHg: 1.8 +/- 0.2 and 6.7 +/- 0.4 nmol kg-1, respectively), with a similar maximal activity (delta MAP: 85 +/- 4 and 81 +/- 2.4 mmHg, respectively). The onset of the big-endothelin-1 vasopressor effect was more rapid (5-6 min) than that of big-endothelin-2 (10-13 min). Big-endothelin-3 was found to induce only a potent, long lasting (> 35 min) hypertension, with a maximal effect of 75 +/- 4.6 mmHg at 10 nmol kg-1 and an ED50 mmHg of 6.5 +/- 0.4 nmol kg-1. The onset of this effect was much slower (20-25 min) than that of the other proendothelins. Pressor responses induced by big-endothelin-1, -2 and -3 (3, 15 and 10 nmol kg-1, respectively) were markedly reduced (60, 80 and 100%) in the presence of phosphoramidon (10 mg kg-1, i.v.). Thiorphan (10 mg kg-1, i.v.) did not inhibit the effects of big-endothelin-1, -2 and -3. 3. In the electrically stimulated rat vas deferens, endothelin-I and -2 were found to be equipotent enhancers of the twitch response (EC100%: 4.0 +/- 0.4 nm and 7.9 +/- 4.8 nm, respectively), both about 3-4 fold as active as endothelin-3 (EC100%: 19 +/- 2.5 nM). Endothelin-1 and -3 showed a comparable maximalstimulatory effect (Emax: 296 +/- 30 and 262 +/- 24%) while endothelin-2 was less active (Emax: 194 +/- 30%).4. Big-endothelin-l and -2 were potent enhancers of the twitch response too (EC 100,%: 10.0 +/- 2.6 nM and 21.6 +/- 3.2 nM, respectively), with a comparable maximal stimulatory effect (Emax: 254 +/- 22 and 264 +/-24%). Big-endothelin-3 was found to be less potent (EC,100%: 275 +/- 21 nM), but retained a marked potentiating effect (Emax: 200 +/- 38%). Phosphoramidon, but not thiorphan, concentration-dependently(10 and 100 microM) reduced big-endothelin-1 (58 and 86% respectively) and big-endothelin-2 (21 and 56%)-mediated responses. Conversely, the big-endothelin-3 effect was reduced by phosphoramidon only at 100 microM (-70%), while thiorphan acts concentration-dependently (31 and 71% at 10 and 100 microM respectively); thus, in the rat vas deferens, big-endothelin-I and -2 were as potent as their corresponding endothelins, while big-endothelin-3 was about 20 times less potent than endothelin-3.5. The increasing effect of endothelin-2 (194 +/- 30% over baseline) was significantly enhanced by either 10 microM phosphoramidon (277 +/- 42%) or thiorphan (318 +/- 15%). The endothelin-I and endothelin-3-mediated twitch enhancement was not affected by the two protease inhibitors (10 microM).6. These results suggest that in vivo big-endothelin-1, -2 and -3, are processed through a similar phosphoramid on-sensitive enzymatic pathway although with different apparent affinity. This enzymatic process is probably attributable to a neutral endoprotease, distinct from neutral-endopeptidase 24.11(NEP). On the other hand, a NEP-like enzymatic activity may be involved, in the rat vas deferens, in the activation of big-endothelin-3 to endothelin-3 and in the metabolism of endothelin-2, but not of endothelin-I or endothelin-3.
Br J Pharmacol 1993 Sep
PMID:Comparison of the cardiovascular and neural activity of endothelin-1, -2, -3 and respective proendothelins: effects of phosphoramidon and thiorphan. 810 8

In the present study we estimated the periodic profiles and variance structure of systolic blood pressure, diastolic blood pressure, heart rate and mean arterial pressure by using an autoregressive model of power spectrum, Maximum Entropy Method (MEM) in 8 patients with primary aldosteronism, during long-term therapy with nicardipine slow release. The four blood pressure variables were measured at 30-min intervals, using a noninvasive device (Spacelabs 90202) in 8 hypertensive patients of whom 6 with idiopathic aldosteronism (IHA) and 2 with dexamethasone-suppressible aldosteronism (DSH), before and after 24 weeks of 80 mg nicardipine daily. Blood pressure data were processed by MEM and spectral profiles were obtained. During nicardipine therapy all patients showed a significant decrease of 24-h ambulatory blood pressure values (p < 0.01). Before therapy, spectrum analysis by MEM indicated the presence of high frequency distribution of peaks for SBP, DBP, MAP and HR. The MEM power spectrum showed an increase in amplitude of sharp peaks of systolic, diastolic, MAP and heart rate in all patients after therapy at 24 h corresponding to the circadian rhythm blood pressure. Furthermore, the trend of these variables synchronized themselves in the same period after 24 weeks of nicardipine therapy, with spectral patterns of blood pressure similar to those of normotensive subjects. This chronobiologic approach, by Maximum Entropy Method, may be used as an alternative statistical analysis to search for possible rhythmic behavior of ambulatory blood pressure data before and after pharmacological treatment in secondary hypertensive patients.
Blood Press 1993 Sep
PMID:Twenty-four-hour power spectral analysis by maximum entropy method of blood pressure in primary hyperaldosteronism. 820 12

Angiotensin I converting enzyme inhibition (ACEi) has been shown to lower urinary protein excretion in human renal disease. The mechanism of this antiproteinuric effect is hypothesized to be mediated by changes in renal hemodynamics. However, clinical studies suggest that the effect on renal hemodynamics is fully established immediately after the start of treatment, whereas others show the antiproteinuric effect to reach maximum only after several weeks. To clarify this issue we studied the course of renal hemodynamics, blood pressure and proteinuria during 28 days of ACEi (enalapril 10 mg oid) in nine patients with proteinuria due to non-diabetic renal disease. The effect of ACEi on blood pressure and renal hemodynamics was already maximal within few hours after start of treatment, and remained stable thereafter: MAP was lowered with 8.6 +/- 1.9%, 10.6 +/- 2.1%, 12.8 +/- 2.3% and 12.9 +/- 2.5%, while FF fell 23.0 +/- 2.0%, 17.0 +/- 2.6%, 16.8 +/- 2.8% and 15.9 +/- 4.0% on days 1, 7, 14 and 28 of ACEi, respectively. However, the antiproteinuric effect only gradually reached its maximum on day 28. Urinary protein excretion decreased with 10.9 +/- 6.1%, 32.7 +/- 6.2%, 46.3 +/- 2.5% and 54.0 +/- 2.5% on days 1, 7, 14 and 28 of ACEi, respectively. After drug withdrawal all parameters returned towards baseline. We conclude that a dissociation occurs in the course of the ACEi induced effects on hemodynamics and urinary protein excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Kidney Int 1993 Sep
PMID:Dissociation between the course of the hemodynamic and antiproteinuric effects of angiotensin I converting enzyme inhibition. 823 Oct 31

Two groups of 11 ICU respiratory patients ventilated with PSV have been sedated with propofol (group I) or with midazolam (group II). After the endovenous administration of the induction dose (propofol 1.5 mg/kg; midazolam 0.15 mg/kg) sedation was obtained with continuous infusion of the drugs (propofol 2 mg/kg/h; midazolam 0.24 mg/kg/h). In this setting the Authors evaluated the level of sedation (Ramsey scale) and the side effect of the two drugs. At induction midazolam caused a reduction of tidal volume for some minutes and a greatest sedation in comparison with propofol, while propofol caused reduction of MAP (p < 0.01) and transitory apnoea. Even if during the infusion of propofol the level of sedation decreased with time (p < 0.05; y = -0.0357 x + 3.07) it was more stable in comparison with that registered during continuous infusion of midazolam (p < 0.01; y = -0.2018 x + 5.19.
Minerva Anestesiol 1993 Sep
PMID:[Propofol-midazolam in continuous infusion for sedation in intensive care]. 827 66

Haloperidol (HPD: 0.0063, 0.025, 0.1 and 0.4 mg/kg, s.c.) reduced dose-dependently the ambulation-increasing effect of methamphetamine (MAP: 2 mg/kg, s.c.) in mice. The repeated administration of MAP elicited a sensitization to its ambulation-increasing effect, and the development of sensitization was inhibited when MAP was administered in combination with HPD in the repeated administration schedule. However, any dose of HPD could not ameliorate the established MAP sensitization. Whereas, the mice experienced the repeated treatment with HPD 0.4 mg/kg showed an increase in the MAP sensitivity. The present results suggest that HPD, at comparatively higher doses, produces a denervation supersensitivity of postsynaptic dopamine receptors, and shows protective action on the development of MAP sensitization. However, it is also suggested that the established MAP sensitization is irreversible even after the treatment with HPD.
Jpn J Psychiatry Neurol 1993 Sep
PMID:Effects of haloperidol on the methamphetamine sensitization: assessment by ambulatory activity in mice. 830 85

Increased routing of glucose through the hexosamine-biosynthetic pathway has been implicated in the development of glucose-induced insulin resistance of glucose transport in cultured adipocytes. Because both glucosamine and glucose enter this pathway as glucosamine-6-phosphate, we examined the effects of preincubation with glucosamine in isolated rat diaphragms and in fibroblasts overexpressing the human insulin receptor (HIR-cells). In muscles, pre-exposure to glucosamine inhibited subsequent basal and, to a greater extent, insulin-stimulated glucose transport in a time- and dose-dependent manner and abolished the stimulation by insulin of glycogen synthesis. Insulin receptor number, activation of the insulin receptor tyrosine kinase in situ and after solubilization, and the total pool of glucose transporters (GLUT4) were unaffected, and glycogen synthase was activated by glucosamine pretreatment. In HIR-cells, which express GLUT1 and not GLUT4, basal and insulin-stimulated glucose transport were unaffected by glucosamine, but glycogen synthesis was markedly inhibited. Insulin-stimulated activation of protein kinases (MAP and S6) was unaffected, and the fractional velocity and apparent total activity of glycogen synthase was increased in glucosamine-treated HIR-cells. In pulse-labeling studies, addition of glucosamine during the chase prolonged processing of insulin proreceptors to receptors and altered the electrophoretic mobility of proreceptors and processed alpha-subunits, consistent with altered glycosylation. Glucosamine-induced insulin resistance of glucose transport appears to be restricted to GLUT4-expressing cells, i.e., skeletal muscle and adipocytes; it may reflect impaired translocation of GLUT4 to the plasmalemma. The glucosamine-induced imbalance in UDP sugars, i.e., increased UDP-N-acetylhexosamines and decreased UDP-glucose, may alter glycosylation of critical proteins and limit the flux of glucose into glycogen.
Diabetes 1993 Sep
PMID:Pre-exposure to glucosamine induces insulin resistance of glucose transport and glycogen synthesis in isolated rat skeletal muscles. Study of mechanisms in muscle and in rat-1 fibroblasts overexpressing the human insulin receptor. 834 45

We have constructed a plasmid (pHE2) in which the synthetic human alpha- and beta-globin genes and the methionine aminopeptidase (Met-AP) gene from Escherichia coli are coexpressed under the control of separate tac promoters. The Hbs were expressed in E. coli JM109 and purified by fast protein liquid chromatography, producing two major components, a and b. Electrospray mass spectrometry shows that at least 98% and about 90% of the expressed alpha and beta chains of component a, respectively, have the expected masses. The remaining 10% of the beta chain in component a corresponds in mass to the beta chain plus methionine. In component b, both alpha and beta chains have the correct masses without detectable N-terminal methionine (< 2%). These results have been confirmed by Edman degradation studies of the amino-terminal sequences of the alpha and beta chains of these two recombinant Hb (rHb) samples. rHbs from components a and b exhibit visible optical spectra identical to that of human normal adult Hb (Hb A). Component a and Hb A have very similar oxygen-binding properties, but component b shows somewhat altered oxygen binding, especially at low pH values. 1H-NMR spectra of component a and Hb A are essentially identical, whereas those of component b exhibit altered ring current-shifted and hyperfine-shifted proton resonances, indicating altered heme conformation in the beta chain. These altered resonance patterns can be changed to those of Hb A by converting component b to the ferric state and then to the deoxy state and finally back to either the carbonmonoxy or oxy form. Thus, our E. coli expression system produces native, unmodified Hb A in high yield and can be used to produce desired mutant Hbs.
Proc Natl Acad Sci U S A 1993 Sep 01
PMID:Production of unmodified human adult hemoglobin in Escherichia coli. 836 71

Mitogen-activated protein kinases (p42mapk and p44mapk) are serine/threonine kinases that are activated rapidly in cells stimulated with various extracellular signals. This activation is mediated via MAP kinase kinase (p45mapkk), a dual specificity kinase which phosphorylates two key regulatory threonine and tyrosine residues of MAP kinases. We reported previously that the persistent phase of MAP kinase activation is essential for mitogenically stimulated cells to pass the "restriction point" of the cell cycle. Here, using specific polyclonal antibodies and transfection of epitope-tagged recombinant MAP kinases we demonstrate that these signaling protein kinases undergo distinct spatio-temporal localization in growth factor-stimulated cells. In G0-arrested hamster fibroblasts the activator p45mapkk and MAP kinases (p42mapk, p44mapk) are mainly cytoplasmic. Subsequent to mitogenic stimulation by serum or alpha-thrombin both MAP kinase isoforms translocate into the nucleus. This translocation is rapid (seen in 15 min), persistent (at least during the entire G1 period up to 6 h), reversible (by removal of the mitogenic stimulus) and apparently 'coupled' to the mitogenic potential; it does not occur in response to nonmitogenic agents such as alpha-thrombin-receptor synthetic peptides and phorbol esters that fail to activate MAP kinases persistently. When p42mapk and p44mapk are expressed stably at high levels, they are found in the nucleus of resting cells; this nuclear localization is also apparent with kinase-deficient mutants (p44mapk T192A or Y194F). In marked contrast the p45mapkk activator remains cytoplasmic even during prolonged growth factor stimulation and even after high expression levels achieved by transfection. We propose that the rapid and persistent nuclear transfer of p42mapk and p44mapk during the entire G0-G1 period is crucial for the function of these kinases in mediating the growth response.
J Cell Biol 1993 Sep
PMID:Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase (p45mapkk) in fibroblasts. 839 45

The mitogen-activated protein kinases (MAP kinases) p42mapk and p44mapk are serine/threonine kinases rapidly activated in cells stimulated with various extracellular signals by dual phosphorylation of tyrosine and threonine residues. They are thought to play a pivotal role in integrating and transmitting transmembrane signals required for growth and differentiation. Here we demonstrate that activation of these ubiquitously expressed MAP kinases is essential for growth. To specifically suppress MAP kinase activation in fibroblasts, we transiently expressed either the entire p44mapk antisense RNA or p44mapk kinase-deficient mutants (T192A or Y194F). As expected, and through independent mechanisms, both approaches strongly inhibited MAP kinase activation. The antisense reduced the expression of endogenous p42mapk and p44mapk by 90%, whereas overexpression of the T192A mutant inhibited growth factor activation of both endogenous MAP kinases by up to 70%. As a consequence, we found that the antisense as well as the T192A mutant of p44mapk inhibited growth factor-stimulated gene transcription (collagenase promoter assay with chloramphenicol acetyltransferase reporter) and cell growth. These effects were proportional to the extent of MAP kinase inhibition and reversed by coexpression of the wild-type p44mapk. Therefore we conclude that growth factor activation of p42mapk and p44mapk is an absolute requirement for triggering the proliferative response.
Proc Natl Acad Sci U S A 1993 Sep 15
PMID:Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation. 839 1

The effect of prostaglandin E1 (PGE1; Prostavasin), a powerful platelet blocking agent, was assessed on various new synthetic or biological prostheses in a 6-min in vivo extra corporal arterio-venous (AV) shunt. In eight anaesthetised and heparinised minipigs (weight 25.1 +/- 1.9 kg) the following materials were tested before and during PGE1 infusion (alprostadil-alpha-CD; 40 micrograms/50 ml NaCl/50 min or 0.8 microgram/min): PTFE, (Gore-tex, TW, 4 mm ID); Xenograft, Biologic (Solcograft, 5 mm ID), (non-porous) and Dacron (Atrium, 4 mm ID); polyurethane 1 (Braun-Melsungen, 4 mm ID); polyurethane 2 (S. Gogolewski, 4 mm ID), (porous). Technetium-labelled platelet deposition and blood flow were measured; morphology was assessed by scanning electron microscopy (SEM) and histology. Compared to control levels, PGE1 infusion had a significant systemic effect on mean arterial pressure required by the protocol (MAP 82.6 vs. 66.6 mm Hg; p < 0.001) and flow (173.6 vs. 134.8 mm/min; p < 0.001). Standardised platelet counts per area showed a marked overall decrease from 197 to 130 counts/min/mm2; NS). The morphological assessment by SEM showed a slight increase of surface cellular deposition (score: 6.7 vs. 8.3), the histology score being unchanged (3.9 vs. 3.7). Looking at deposition of platelets for each prosthesis, the porous materials showed a net improvement after PGE1 treatment as compared to non-porous materials. We conclude that PGE1 may be of benefit by reducing platelet deposition in synthetic porous vascular prostheses in the early phase.
Eur J Vasc Surg 1993 Sep
PMID:Experimental assessment of thrombogenicity in vascular prostheses before and during prostaglandin E1 treatment. 840 91


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