Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin (ET-1) receptors were studied in the C-6 glia cell line. ET-1 binds to C-6 cells in a temperature- and time-dependent manner, with an apparent Kd of 1.16 +/- 0.07 10(-10) M and a Bmax of 96,500 +/- 6000 sites/cell (mean +/- SEM, n = 27). Stimulation of protein kinase C (PKC) with the diacylglycerol (DAG) analog phorbol 12-myristate 13-acetate (PMA) resulted in a decrease in the number of receptors in a dose-dependent manner. Inhibition of PKC with H-7 eliminated the effect of PMA on the reduction of binding sites. Treatment with exogenous 1-oleoyl-2-acetyl-sn-glycerol (OAG) and 1,2-dioctanoyl-sn-glycerol (DOG), release of endogenous DAG with phospholipase C, and inhibition of the metabolism of DAG with the diacylglycerol kinase inhibitor R 59022 also resulted in a decrease in the number of receptors. The effect of these agents was inhibited by H-7. ET-1-mediated down-regulation of receptors was also demonstrated, but the down-regulation was not affected by H-7 or by depletion of cellular PKC with chronic, high dose of PMA. Internalization constants of ET-1-receptor complex was also measured according to the model of Wiley and Cunningham (Cell 25 (1981) 433). PMA- and ET-1-mediated down-regulation of receptors was associated with an increase in the endocytosis constant for the hormone-receptor complex and a decrease in the rate of insertion of receptor into the plasma membrane. PMA, but not ET-1, increased the rate of endocytosis of unoccupied receptors. Radioiodinated ET-1 was crosslinked to the receptor after binding, extracted and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A band at 66 kDa was obtained. These studies show that ET-1 and PKC activation produce down-regulation of ET-1 membrane receptors and that ET-1-mediated down-regulation probably does not involve the activation of PKC.
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PMID:ET-1 receptors in C-6 cells: homologous down-regulation and modulation by protein kinase C. 216 63

1. In eight healthy volunteers we compared leg blood flow, as determined in a calf segment by strain-gauge plethysmography, with the flow measured by a constant-rate infusion of Indocyanine Green dye into the femoral artery. The representativeness of the calf segment was evaluated by complementary measurements with additional strain gauges attached around the proximal and distal crural and the distal thigh segments (n = 6). Furthermore, we investigated the influence of the catheterization procedure and a simulated vascular puncture, as well as repeated venous occlusions, on blood flow and on arterial and femoral venous substrate concentrations and blood gases (n = 8). 2. The leg blood flow measured by dye dilution was 0.31 +/- 0.03 litre/min (mean +/- SEM). The blood flow in the calf segments was 14.8 +/- 1.6 ml min-1 litre-1 and no difference between the legs was observed. Extended to the whole leg the plethysmographic blood flow was 0.17 +/- 0.01 litre/min and thus lower (43 +/- 7%, P less than 0.001) than the flow determined by the indicator-dilution method. Blood flow in the legs was not influenced by catheterization or sham punctures of the vessels or by repeated venous occlusions. 3. The concentrations of glucose, lactate and glycerol, as well as blood gas variables, in arterial and femoral venous blood did not change during the study or decreased so slightly (pH and lactate) that the arteriovenous difference was not influenced. 4. We conclude that the blood flow of the total leg cannot be satisfactorily estimated from strain-gauge plethysmography of a single calf segment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of dye-dilution and plethysmographic blood flow measurements: an evaluation of the influence of invasive techniques on blood flow and on arterial and femoral venous substrate variables in man. 216 95

The metabolic effects of the local administration of propranolol were determined in seven patients undergoing cholecystectomy. Measurements were carried out in the early postoperative period before and after infusion of 2 mg of intraarterial propranolol into the femoral artery of one leg using the other leg as control. Blood flow and arterio-venous concentration differences for oxygen, glucose, lactate, alanine, glycerol and total FFAs were determined. Uptake and release of FFAs were determined by using a tracer technique. The statistical analyses were based on differences between the test and the control leg in changes following the blockade. Glycerol release was significantly more suppressed in the test leg than in the control leg. No difference between the legs was seen in the uptake of oxygen, FFA and glucose or the release of lactate and alanine. The arterial concentration of propranolol was 6.07 +/- 0.72 ng ml-1 (mean +/- SEM). This study indicates that a local beta-blockade by intra-arterial propranolol infusion after surgery slightly reduces the postoperative lipolysis in leg tissues but does not influence or only marginally influences leg blood flow and oxygen uptake or the exchange of glucose, lactate and alanine after moderate surgical trauma.
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PMID:Influence of local beta-adrenoceptor blockade on exchange of fat and glucose in the human leg after surgery. 231 26

Small (Sf 20-100) very low density lipoprotein (VLDL) particles were prepared by density gradient ultracentrifugation of plasma from normolipidemic and type IV hypertriglyceridemic post-infarction patients and healthy controls. The small VLDL separated from the plasma of severely hypertriglyceridemic post-infarction patients were found to contain twice the amount of cholesteryl esters per particle, compared with small VLDL from normolipidemic patients and healthy controls. There was a linear increase in the percentage of cholesterol that was esterified in the small VLDL with the serum VLDL triglyceride concentration (r = 0.66). When incubated for two hours with bovine lipoprotein lipase in excess and bovine albumin as a free fatty acid acceptor at one and the same triglyceride concentration in the medium, the end-product isolated by ultracentrifugation varied as a function of the serum VLDL triglyceride level. The amount of glyceride-glycerol recovered after two hours of incubation with lipoprotein lipase was 13.3 +/- 1.3% (mean +/- SEM) of the initial values and did not correlate with the VLDL triglyceride level. With rising serum VLDL triglyceride concentration, the product isolated in the low density lipoprotein (LDL) density region (1.006 less than d less than 1.063 kg/l) contained more total cholesterol and phospholipids. The linear correlation coefficients for these relations were 0.65 and 0.58 for cholesterol and phospholipids respectively. The ratio of total cholesterol to insoluble protein in the LDL density range after lipolysis rose with increasing serum VLDL triglyceride level (r = 0.68). The end-product was further characterized by density gradient ultracentrifugation of the incubate. In vitro LDL derived by lipolysis of normolipidemic small VLDL was denser than in vitro LDL of hypertriglyceridemic small VLDL. A significant relation was found between the percentage of cholesteryl esters of total cholesterol in the substrate and the relative amount of total cholesterol recovered in the LDL density fraction after lipolysis (r = 0.69). We suggest that the enrichment with cholesteryl esters of small VLDL from type IV hypertriglyceridemic patients is caused by lipid transfer from LDL and high density lipoprotein (HDL) and that the change in VLDL particle composition influences the precursor-product relationship to LDL.
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PMID:Abnormalities of composition and of in vitro lipolysis products of human small very low density lipoproteins in hypertriglyceridemia. 236 Sep 14

To determine the effects of neutralizing exercise systemic acidosis via the intravenous route upon endurance and metabolic responses, eight lean, normal, postabsorptive men exercised to exhaustion at about 80% of their VO2 max (69 +/- 3%, mean +/- SEM, of maximum power output) on a cycle ergometer. Exercise studies were performed either with no infusion (control) or with a total infusion volume of about 1.5 L, mainly as 1.3% sodium bicarbonate or as 0.9% sodium chloride (NaCl), infused (double-blind) throughout exercise. The sodium bicarbonate was to prevent acid-base change, the sodium chloride was as a control for the volume infused. Arterialized venous blood and breath-by-breath analysis of expired gases were obtained. [H+] (nmol.L-1) and [HCO3-] (mmol.L-1) at exhaustion were similar in control and NaCl (46.5 +/- 1.8, 19.9 +/- 0.9), but remained unchanged from rest values with bicarbonate (38.4 +/- 0.9, 24.8 +/- 1.5, p less than 0.005 vs control and NaCl). At exhaustion, VO2, VCO2, RER, heart rate, and systolic BP as well as FFA, glycerol, alanine, insulin, norepinephrine, and epinephrine did not differ among protocols. Endurance was markedly prolonged (p less than 0.01) with bicarbonate (31.9 +/- 5.8 min) and NaCl (31.8 +/- 4.1 min) compared with the control (19.0 +/- 2.9 min) condition. Plasma glucose at exhaustion was higher (p less than 0.025) in the control compared to bicarbonate and NaCl experiments, while lactate was higher (p less than 0.025) in the bicarbonate than in the control and NaCl experiments. Thus, the prolonged endurance with sodium bicarbonate infusion could not be explained either by its effect of maintaining blood acid-base equilibrium or concomitant metabolic changes.
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PMID:Intravenous bicarbonate and sodium chloride both prolong endurance during intense cycle ergometer exercise. 240 23

Twelve-hour metabolic profiles have been measured in six patients with insulinoma and results compared with normal subjects of similar age and weight. Fasting blood glucose was lower (mean +/- SEM 2.9 +/- 0.3 mmol/l vs 5.0 +/- 0.2 mmol/l) and plasma insulin higher (20.0 +/- 3.9 mU/l vs 7.2 +/- 1.6 mU/l) in insulinoma patients. Over the 12-h period blood glucose, pyruvate and glycerol were significantly lower, and plasma insulin, blood lactate, alanine and plasma non-esterified fatty acids (NEFA) significantly higher in insulinoma patients. Overall the concentration of blood total ketone bodies was significantly higher in insulinoma patients. Values were higher in the early part of the day but lower later in the day and did not show the marked pre-meal rise observed in the normal subjects. The raised NEFA and ketone bodies are of particular interest as they may be a source of fuel supply in the presence of relative glucose deficiency.
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PMID:Metabolic profiles in patients with insulinoma. 255 Jan 66

The aim of the present study was to determine the effect of i.v. inosine on myocardial substrate uptake and function in the in situ dog heart. Inosine was infused i.v. at a rate of 5 mg kg min-1 in eight closed-chest pentobarbital anaesthetized dogs. Inosine caused a 46% decrease (P less than 0.01) in plasma free fatty acids (FFA), a 15% decrease (P less than 0.05) in plasma glycerol, an 18% decrease (P less than 0.05) in plasma glucose and a 46% increase (P less than 0.01) in blood lactate. This was associated with a 55% decrease (P less than 0.01) in myocardial FFA uptake and a 72% increase in lactate uptake, while glucose uptake remained unchanged. These metabolic changes were associated with a five-fold increase (P less than 0.05) in arterial insulin. Inosine caused an 18% increase (P less than 0.01) in myocardial blood flow without changing MVO2. There was a 33% increase (P less than 0.01) in LV dP/dtmax, a decrease in LVEDP from 4.9 +/- 0.9 (mean +/- SEM) to 0.9 +/- 0.3 mmHg (P less than 0.05) and a 24% decrease (P less than 0.01) in systemic vascular resistance. Inosine caused a transient 38% increase (P less than 0.05) in pulmonary vascular resistance. In conclusion, in addition to a positive inotropic effect and vascular effects inosine was found to cause release of insulin and to shift myocardial metabolism towards increased uptake of carbohydrates relative to FFA.
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PMID:Inosine causing insulin release and increased myocardial uptake of carbohydrates relative to free fatty acids in dogs. 265 Sep 58

To study whether hyperthermia reproduces hormonal and metabolic responses seen in stress states such as mild infections, six normal male subjects underwent (i) a 3-h hot bath and (ii) a 3-h thermoneutral control period. During the hot bath body temperature rose by 1.2 +/- 0.03 degrees C (mean +/- SEM) and significant peaks of circulating growth hormone (56 +/- 9 vs 7 +/- 4 mU/l), adrenaline (310 +/- 34 vs 152 +/- 39 pmol/l), glucagon (19.2 +/- 4.3 vs 11.8 +/- 2.3 pmol/l) and cortisol were recorded together with slight hyperinsulinaemia (6.5 +/- 1.3 vs 5.3 +/- 1.0 mU/l, P less than 0.05). Hyperthermia was also accompanied by significant increases in circulating levels of free fatty acids (0.93 +/- 0.1 vs 0.46 +/- 0.1 mmol/l), 3-hydroxybutyrate (196 +/- 67 vs 50 +/- 18 mumol/l), glycerol (102 +/- 10 vs 48 +/- 5 mumol/l) and lactate. Blood alanine decreased and blood glucose remained constant. When an intravenous glucose tolerance test was performed during the last hour of hyperthermia signs of impaired first phase and enhanced second phase insulin responses were recorded. Calculated values for glucose disappearance also deteriorated (1.34 +/- 0.19 vs 2.04 +/- 0.50 %/min, P less than 0.05). We conclude that hyperthermia mimics most major metabolic and hormonal changes observed during mild infection and could provide a model to study these conditions.
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PMID:Metabolic and hormonal responses to exogenous hyperthermia in man. 268 66

We tested the hypothesis that protein kinase C might play a role in the biosynthesis of platelet-activating factor (paf-acether) in human neutrophils. PMA but not its inactive analog 4-alpha-phorbol-12,13-didecanoate induced lyso paf-acether production, followed by acetyltransferase activation, leading to paf-acether synthesis and release. Moreover, PMA was twice as powerful compared to opsonized zymosan (OPZ). 1-Oleoyl-2-acetyl-glycerol also induced acetyltransferase activation and paf and lyso paf production. The paf-acether formed by PMA or OPZ stimulation was composed of alkyl chains C16:0 (84.3 +/- 5% and 80.7 +/- 3.5%, respectively, and C18:0 (15.7 +/- 5% and 19.3 +/- 3.5%, respectively, means +/- SEM) as assessed by gas chromatography-electron capture detection. The inhibitor of protein kinase C, D-sphingosine, markedly decreased paf and lyso paf production and acetyltransferase activation in PMA- as well as OPZ-stimulated neutrophils. These results strongly suggest the involvement of protein kinase C in signal transduction during cell stimulation, leading to the paf biosynthesis.
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PMID:Biosynthesis of paf-acether. X. Phorbol myristate acetate-induced paf-acether biosynthesis and acetyltransferase activation in human neutrophils. 273 70

Nine subjects (VO2max 65 +/- 2 ml.kg-1.min-1, mean +/- SEM) were studied on two occasions following ingestion of 500 ml solution containing either sodium citrate (C, 0.300 g.kg-1 body mass) or a sodium chloride placebo (P, 0.045 g.kg-1 body mass). Exercise began 60 min later and consisted of cycle ergometer exercise performed continuously for 20 min each at power outputs corresponding to 33% and 66% VO2max, followed by exercise to exhaustion at 95% VO2max. Pre-exercise arterialized-venous [H+] was lower in C (36.2 +/- 0.5 nmol.l-1; pH 7.44) than P (39.4 +/- 0.4 nmol.l-1; pH 7.40); the plasma [H+] remained lower and [HCO3-] remained higher in C than P throughout exercise and recovery. Exercise time to exhaustion at 95% VO2max was similar in C (310 +/- 69 s) and P (313 +/- 74 s). Cardiorespiratory variables (ventilation, VO2, VCO2, heart rate) measured during exercise were similar in the two conditions. The plasma [citrate] was higher in C at rest (C, 195 +/- 19 mumol.l-1; P, 81 +/- 7 mumol.l-1) and throughout exercise and recovery. The plasma [lactate] and [free fatty acid] were not affected by citrate loading but the plasma [glycerol] was lower during exercise in C than P. In conclusion, sodium citrate ingestion had an alkalinizing effect in the plasma but did not improve endurance time during exercise at 95% VO2max. Furthermore, citrate loading may have prevented the stimulation of lipolysis normally observed with exercise and prevented the stimulation of glycolysis in muscle normally observed in bicarbonate-induced alkalosis.
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PMID:The effect of citrate loading on exercise performance, acid-base balance and metabolism. 276 67


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