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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The demonstration that endothelin (ET) induces rat uterine contraction, coupled with the observation that ET is present in human amniotic fluid, suggests that the myometrium may be an important target organ for this hormone. We show that in quiescent human myometrial cells ET produced a dose-dependent increase in cytosolic free Ca2+ (Cai2+), which was markedly attenuated when the cells were studied in Ca2(+)-free media. Preincubation with nicardipine, diltiazem, or verapamil reduced the ET-evoked Cai2+ transient by 30, 40, and 65%, respectively. The presence of voltage sensitive Ca2+ channels was demonstrated by Mn2+ quenching of fura-2. Activation of the Na+/H+ antiport could not be demonstrated with ET stimulation. In nonquiescent cells, the ET-evoked Cai2+ transient was significantly reduced, while the response to oxytocin was retained. This is at least partially explained by a reduction in Bmax (maximal binding capacity) for ET (mean +/- SEM) from 3,506 +/- 268 binding sites/cell in quiescent cells to 2,411 +/- 300 binding sites/cell, as well as 72% increase in Kd (equilibrium dissociation constant), in the nonquiescent cells. We conclude that, in human myometrial cells, ET and oxytocin modulate Cai2+ through independent receptors and propose that ET, like oxytocin, is an important endogenous modulator of uterine contractility.
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PMID:Endothelin- and oxytocin-induced calcium signaling in cultured human myometrial cells. 184 47

Cells in many specimens of human ventricle can exhibit either of two stable levels of diastolic potential (DP) when exposed to 4 mM K+ in vitro (i.e., -78 +/- 4 mV or -45 +/- 5 mV, mean +/- SEM). In this report we show that the DP of some partially depolarized human ventricular cells developed a sustained 25-35 mV hyperpolarization (n = 28) when bath K+ concentration (K+b) was raised from 4 to 7 mM. On return of K+b to 4 mM, the DP of most, but not all, of these cells returned to the original depolarized levels. In other cells, the transition between the two levels of DP occurred at variable K+b ranging from 1 to 20 mM. We investigated the ionic mechanism(s) underlying the shifts between the two levels of potential by studying the K+ dependence of the DP in partially depolarized cells in 22 specimens of human ventricle. DP hyperpolarized an average of 25.6 mV (from -44.4 +/- 1.3 to -70.0 +/- 1.3 mV; n = 25) when K+b was increased from 4 to 7 mM. Intracellular K+ activity, determined by K+-selective microelectrodes, was within the range of normal reported for other mammalian species (106.7 +/- 4.4 mM in 4 mM K+; n = 22) and was unaffected by increasing K+b to 7 mM (111.7 +/- 6.6 mM; n = 6). Ba2+ (0.05 mM), a blocker of the inward rectifying K+ current, reversibly prevented the hyperpolarization, whereas acetylstrophanthidin (9 microM) failed to inhibit it. These results suggest that the hyperpolarization was due to a K+-dependent increase in K+ permeability and that electrogenic sodium pumping did not contribute significantly to the process. The ionic basis of the depolarization from a hyperpolarized level of DP also was investigated. Decreasing bath Na+ concentration and exposure to 30 microM tetrodotoxin did not prevent the depolarization. However, the depolarization could be inhibited by 2 mM Mn2+. These findings suggest that the depolarization may have been due to a Mn2+-sensitive inward current.
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PMID:Two stable levels of diastolic potential at physiological K+ concentrations in human ventricular myocardial cells. 229 38

Nutritional status of manganese in 10 adult males was monitored through a 47-d period by measuring manganese in serum and urine and by chemically analyzing duplicate portions of all foods and beverages consumed on 3 d, with computer analysis of dietary records for 10 additional days. Subjects consumed 0.52-5.33 mg Mn/d; 50% of the time they consumed less than the 1980 Estimated Safe and Adequate Daily Dietary Intake for manganese. Subjects on average (+/- SEM) excreted 7.0 +/- 0.5 nmol Mn/g creatinine; their average serum manganese concentration was 19.3 +/- 1 nmol/L. These potential indices of manganese exposure were not correlated with the subjects' dietary intakes of manganese or other minerals. However, serum manganese concentrations tended to be elevated (p less than 0.064) in five subjects who consumed 15 mg chelated Mn/d for 7 d.
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PMID:Intake, serum concentrations, and urinary excretion of manganese by adult males. 230 52

We have characterized specific receptors for tetradecapeptide somatostatin (SS-14) of rat brain using 125I-labeled Tyr11-SS-14([125I-Tyr11]SS-14) as radioligand. [125I-Tyr11]SS-14 binding was sensitive to time, pH, temperature and ionic strength of the buffer, and was optimal in 50mM HEPES/KOH buffer, pH 7.5, at 25 degrees C for 60 minutes. Scatchard analysis indicated that the rat forebrain membranes had a single binding site with an apparent dissociation constant (Kd) of 0.522 +/- 0.044 nM and maximum binding capacity (Bmax) was 233 +/- 37 fmol/mg protein (mean +/- SEM). Ca2+, Mg2+, Mn2+ and Co2+ had a significant effect on the specific binding, which indicates that these metal ions might affect somatostatin receptor activity in the brain. Among CNS acting drugs, Ca2+ antagonists, antischizophrenic drugs, antidepressants and anticholinergic drugs had relative effects on [125I-Tyr11]SS-14 bindings to rat cerebral cortex membranes.
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PMID:Biochemical and pharmacological characterization of somatostatin receptors in rat brain. 257 1

Thyrotropin (TSH), stimulators of guanyl nucleotide regulatory protein, (sodium fluoride and guanyl-5'-yl-imido-diphosphate [Gpp(NH)p]) and a stimulator of the catalytic unit of adenylate cyclase (AC) (forskolin) were used to probe the TSH receptor-guanyl nucleotide regulatory protein-cyclase unit in normal and neoplastic thyroid tissue from 17 patients. Eleven of these patients had benign follicular adenomas and six patients had differentiated thyroid carcinomas. An 8000 X g particulate fraction that is rich in thyroid plasma membranes was prepared, and the activity of AC was determined by the conversion of alpha-32P-ATP to P32-cAMP. Thyroid neoplasms had a greater AC response to TSH than did normal thyroid tissue removed from the same patients (p less than 0.001). The AC response to NaF and Gpp(NH)p was greater in the neoplastic thyroid tissue, although in these experiments the increase was not significant. In contrast, the AC response to forskolin was comparable in normal (573 +/- 129) and neoplastic (526 +/- 132) thyroid tissue (mean +/- SEM). The effects of NaF, Gpp(NH)p, and forskolin on AC activity were additive with TSH when used at concentrations for optimal AC activity. Low concentrations of NaF and Gpp(NH)p stimulated AC activity whereas high concentrations of NaF and Gpp(NH)p assayed either together or separately inhibited AC activity. When forskolin and NaF were assayed together there was a greater than additive effect or potentiated effect on activity. Basal AC activity was increased in the presence of manganese (Mn+2) (2 mM) over magnesium (Mg+2) (2 mM) (p less than 0.001), whereas TSH-stimulated (p less than 0.01) and Gpp(NH)p-stimulated AC activity (p less than 0.05) were lower in the presence of Mn+2 than Mg+2. There was an excellent correlation between basal AC activity and AC activity in response to forskolin in both normal and neoplastic thyroid tissue, whereas there was no correlation between basal AC activity and TSH-stimulated AC activity in the thyroid neoplasms. These data suggest that the abnormality responsible for the greater AC response to TSH in neoplastic thyroid tissue is proximal to the catalytic unit of AC and most probably is due to an alteration in the guanyl nucleotide regulatory protein or in the coupling of the guanyl nucleotide regulatory protein to either the receptor or the catalytic unit of AC.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Thyrotropin regulation of adenylate cyclase activity in human thyroid neoplasms. 298 5

To characterize the insulin-like growth factor I (IGF-I) receptor on human erythrocytes, cells were purified from peripheral blood by Ficoll-Hypaque gradient centrifugation and incubated with [125I]IGF-I. Specific binding was maximal at pH 8.0 after 24 h at 4 C and increased linearly with cell number to 3.9 +/- 0.2% (+/- SEM) for 3.0 X 10(9) cells/ml. The Scatchard plot of the binding data was linear, with 7 fmol [125I]IGF-I bound/10(9) cells and an affinity constant (K) of 1.8 X 10(9) M-1. Unlabeled IGF-I inhibited tracer binding half-maximally at 6 ng/ml. Multiplication-stimulating activity (or rat IGF-II) was 40% as potent (ED50, 15 ng/ml), whereas insulin and proinsulin were 30- to 500-fold less potent. A monoclonal antibody to the IGF-I receptor (alpha IR-3) inhibited IGF-I binding by 50% at a 1:1000 dilution and by 80% at a 1:250 dilution. Insulin binding was unaffected by the same dilutions. IGF-I receptor phosphorylation was studied in erythrocyte ghosts prepared by hypotonic lysis and solubilized in 1% Triton. The extract was preincubated with and without 100 ng/ml IGF-I or porcine insulin and incubated with [gamma-32P]ATP in the presence of Mn2+, and the receptor was identified by immunoprecipitation with alpha IR-3 antibody and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IGF-I stimulated 4-fold the incorporation of 32P into a protein of 95,000 mol wt, which was immunoprecipitated by alpha IR-3; insulin produced a 2-fold stimulation of this protein. This protein corresponds to the beta-subunit of the IGF-I receptor. These data demonstrate that human erythrocytes have specific receptors for IGF-I, and that this IGF-I receptor, like the insulin receptor, undergoes ligand-stimulated autophosphorylation. Thus, analysis of erythrocyte IGF-I binding and receptor phosphorylation may be useful tools for the study of patients with a variety of growth disorders.
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PMID:The human erythrocyte insulin-like growth factor I receptor: characterization and demonstration of ligand-stimulated autophosphorylation. 300 55

Progesterone induces in vitro the meiotic cell division of Xenopus full-grown oocytes. Microinjection into oocyte of a solution containing Mg2+ (20 mM) facilitates by one order of magnitude the dose of progesterone which induces 50% of germinal vesicle breakdown. Microinjected in the absence of hormone, Mg2+ and also Mn2+ can induce maturation with efficiencies of, respectively, 24% (SEM = 8; n = 13) and 70% (SEM = 6; n = 23). The dose-response curves of cation-induction of maturation show an optimum of 20 mM for Mg2+ and 15 mM for Mn2+ (pipet concentration); higher doses were less active. Cation-induction of maturation is inhibited when oocytes are preincubated with cholera toxin (500 ng/ml); nevertheless, it cannot be interpreted at the level of cAMP, since both Mg2+ and Mn2+ microinjections provoke an increase in the oocyte cAMP content. Mg2+ induction of maturation is more efficient when oocytes are incubated in trimethylamine at pH 8.2, which is known to increase intracellular pH suggesting an action at the level of alkali pH-sensitive enzymes. Altogether, our results indicate a positive role for Mg2+ ions in the induction of oocyte maturation and raise an attractive hypothesis about the respective roles of cAMP and Mg2+ changes involved in the mechanism of progesterone action. Our results also show that co-injection of 2-glycerophosphate and Mg2+ ions, which are both commonly used in the preparation of the MPF mitotic factors from dividing cells, induces oocyte maturation more efficiently than Mg2+ alone and drastically shortens the kinetics of germinal vesicle breakdown to 1 h 30 min to 2 h 30 min.
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PMID:A possible role for Mg2+ ions in the induction of meiotic maturation of Xenopus oocyte. 302 45

To evaluate a pediatric trace element supplement (Ped-El, Pharmacia) 18 metabolic balance studies were completed in 13 infants (mean birth weight 909 +/- 67 g, x +/- SEM; mean gestational age 27.2 +/- 1 weeks) who received total parenteral nutrition. The supplement supplied 40 micrograms/kg/day of zinc resulting in negative retention of 226 micrograms/kg/day. Copper infused at 20 micrograms/kg/day led to a positive retention of 8 micrograms/kg/day and an increase in serum Cu (p less than 0.05) not related to Cu intakes. Manganese infused at 40 micrograms/kg/day was nearly all retained (88 +/- 16% retention). Iron infused at 120 micrograms/kg/day led to a positive retention of 93 micrograms/kg/day. Although plasma ferritin and percent transferrin saturation were elevated, only plasma Fe values were correlated with Fe intake. This trace element supplement does not appear suitable for very low birth weight preterm infants.
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PMID:Zinc, copper, manganese, and iron balance of parenterally fed very low birth weight preterm infants receiving a trace element supplement. 313 48

The activity of prolinase (EC 3.4.13.8) was studied in cultured skin fibroblasts derived from three patients with deficient prolidase (EC 3.4.13.9). With pro-val as substrate and manganese in the reaction buffer, prolinase activity was higher in prolidase-deficient cells than in control cells (mean (SEM) 917 (67) nmol min-1 mg-1, n = 3, control mean (SEM) 294, (50), n = 11). The Michaelis constants were not different for the pro-val and progly substrates in control and prolidase deficient fibroblasts. However, the constants for Vmax rose for both substrates in deficient cells. These results demonstrate that prolinase activity increases in prolidase-deficient fibroblasts as also shown in the plasma of patients with prolidase deficiency. We suggest that in prolidase-deficient fibroblasts, this rise in prolinase activity constitutes an attempt to compensate for the prolidase deficiency by increasing the greatly reduced intracellular proline pool.
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PMID:Prolinase activity in prolidase-deficient fibroblasts. 314 67

Adverse pulmonary reactions to some nitrofuran antibiotics are thought, in part, to involve production of reactive oxygen radicals. Furazolidone, a nitrofuran antibiotic, causes a dilated cardiomyopathy in domestic turkeys. The mechanism of this drug induced cardiomyopathy is unknown. We investigated the possible role of free radical injury in this heart failure model. Left ventricular lipid peroxidation capacity, assessed by two methods (the thiobarbituric acid reactive substances and lipid hydroperoxides assays respectively), was investigated in five 5-8 week old cardiomyopathic turkeys with severe cardiac dilatation, left ventricular dysfunction and systemic hypotension, and in five control birds. Superoxide dismutase activity, total and manganese, was also measured in the crude left ventricular homogenates. Both lipid peroxidation products were reduced in the myopathic hearts: thiobarbituric acid reactive substances (malondialdehyde) 70(SEM 4) v 86(3) nmol.100 mg protein-1 in controls, p less than 0.02; and lipid hydroperoxides 29(7) v 74(14) nmol.100 mg protein-1, p less than 0.02. Total superoxide dismutase activity was similar in cardiomyopathic and control hearts: 670(26) v 657(105) nitrite units.100 mg protein-1. Although total superoxide dismutase activity was unchanged, we found decreased manganese superoxide dismutase in the dilated hearts compared with controls (54% v 84% of total activity, p less than 0.02). In separate in vitro experiments furazolidone (2-10 mg.g wet weight-1) did not increase malondialdehyde production in turkey (or rat) left ventricular homogenates. These results indicate that cardiomyopathy induced by furazolidone is associated with decreased myocardial lipid peroxidation. Although as yet unexplained, the decrease may be due to a diminished amount of heart lipid susceptible to peroxidation accompanying the process of cardiac hypertrophy and dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced lipid peroxidation in dilated hearts of cardiomyopathic turkeys. 325 24


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