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

The calcium (Ca) metabolism of established human lactation was studied in 40 adult women (mean age 32.4 years) who had been breast-feeding for 6 months (Lac) and in 40 age-matched controls (Con) using fasting urine and blood biochemistry and forearm single-photon bone mineral densitometry (BMD). Serial studies were performed up to 6 months after weaning in Lac women and repeated once in Con women. During lactation the significant findings were (1) a selective reduction (7.1%, P less than 0.03) in BMD at the ultradistal site containing 60% trabecular bone, but not at two more proximal, chiefly cortical bone sites; (2) increased bone turnover affecting bone resorption [fasting hydroxyproline excretion, Lac 2.22 +/- 0.12 mumol/liter GF (mean +/- SEM), Con 1.19 +/- 0.04, P less than 0.001] and affecting bone formation (plasma alkaline phosphatase, Lac 81.9 +/- 2.5 IU/liter, Con 53.5 +/- 2.7, P less than 0.001, and serum osteocalcin, Lac 14.0 +/- 0.7 microgram/liter, Con 7.3 +/- 0.4, P less than 0.001); and (3) renal conservation in the fasting state of both Ca and inorganic phosphate (Pi) with a resultant moderate increase in plasma Pi but not in plasma Ca (total or ionized). There were no differences between the groups in serum parathyroid hormone (PTH, intact and midmolecule assays), 25-hydroxy- and 1,25-dihydroxyvitamin D, nephrogenous cyclic AMP production, or plasma creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Human lactation: forearm trabecular bone loss, increased bone turnover, and renal conservation of calcium and inorganic phosphate with recovery of bone mass following weaning. 234 75

K+ efflux in mouse macrophages exhibited a rate constant (kK) of 0.67 +/- 0.04 (h)-1 (mean +/- SEM of 16 experiments). This was strongly stimulated by increasing concentrations of the Ca2+ ionophore A23187 up to a maximal value of 4.01 +/- 0.25 (h)-1 with an IC50 of 7.6 +/- 1.9 microM (mean +/- SEM of 6 experiments). Similar results were obtained with the Ca2+ ionophore ionomycin. Binding experiments with 3H-dihydroalprenolol revealed a high density of beta-adrenergic receptors (97.5 +/- 5.2 fmol/mg protein) with apparent dissociation constant of 2.03 +/- 0.06 nM. Isoproterenol at a concentration of 10(-6)-10(-5) M induced a two- to threefold stimulation of endogenous levels of cyclic AMP (cAMP). A23187-stimulated K+ efflux was partially inhibited by stimulation of adenylate cyclase with isoproterenol, forskolin or, PGE1; exogenous cAMP; and inhibition of phosphodiesterase with MIX (1-methyl-3-isobutylxanthine). Maximal inhibition of K+ efflux was obtained by simultaneous addition of isoproterenol and MIX. In dose-response curves, the isoproterenol-sensitive K+ efflux was half-maximally inhibited (IC50) with 2-5 X 10(-10) M of isoproterenol concentration. Propranolol was able to completely block the effect of isoproterenol, with an IC50 of about 1-2 X 10(-7) M. Isoproterenol and MIX were also able to partially inhibit ionomycin-stimulated K+ efflux. Isoproterenol and MIX did not inhibit A23187-stimulated K+ efflux in an incubation medium where NaCl was replaced by sucrose (or choline), suggesting the involvement of an Na+:Ca2+ exchange mechanism. Our results show that stimulation of beta-adrenoceptors in mouse macrophages counterbalances the opening of K+ channels induced by the calcium ionophore A23187. This likely reflects a decrease in cytosolic free calcium content via a cAMP-mediated stimulation of Na+:Ca2+ exchange.
 ...
PMID:Stimulation of beta-adrenoceptors inhibits calcium-dependent potassium-channels in mouse macrophages. 243 Sep 85

The retinal pigment epithelium (RPE) from the chick embryo was cultured on permeable support. Using confluent cultures and analysis of the incubation medium, the present study demonstrates that RPE cells cultured on permeable membrane retain functional polarity, a characteristic of the RPE in vivo. The degree of intercellular permeability in the confluent RPE cultures was estimated by following [3H]inulin movement from the apical side to the basal side of the cultures. Twenty-four hours after exposure of the apical side of the culture to [3H]inulin, the 3H concentration in the apical medium remained at 3.4 to 4.4 times of that in the basal medium. The barrier function of RPE disappears in the presence of EDTA. Net unidirectional fluid movement from the apical side of the cultures to the basal side of the cultures is regularly observed in confluent RPE cultures. The rate varies among different preparations of cultures and the highest is 1.60-1.84 microliters/cm2/h. When cultures are given 26 h of [35S]methionine, more than 20 bands with molecular weights ranging from 20,000 to greater than 250,000 Da can be detected in the medium as assessed by autoradiography of SDS-polyacrylamide gels. While six macromolecules appear to be equally concentrated in the basal medium and the apical medium, the majority are in higher concentration in the basal medium. Analysis of the 10% TCA-precipitable fraction of the medium showed that the specific activities in the apical medium and basal medium were 24.0 +/- 0.4 X 10(6) and 46.4 +/- 0.2 X 10(6) (mean +/- SEM, N = 8) cpm/ml/mg RPE protein, respectively. When cultures react with VIP (vasoactive intestinal peptide), the elevated intracellular cyclic AMP is extruded into the medium bathing the cells. However, the rate of extrusion into the basal medium is twice as fast as that into the apical medium. Electron microscopy of the confluent RPE cultures shows morphological polarization of the cells. The intercellular spaces appear to be closed at the apical side of the cells by junctional complexes consisting of tight junctions, zonular adherens junctions, and gap junctions.
 ...
PMID:The chick retinal pigment epithelium grown on permeable support demonstrates functional polarity. 253 34

In order to study the regulation of beta-adrenergic receptor number and function in response to prolonged physical effort, lymphocytic beta-adrenoceptor density (determined by (-)[125I]iodocyanopindolol binding), lymphocytic basal and isoproterenol-stimulated cyclic AMP (cAMP) production and concentrations of plasma catecholamines were measured before and during 3 h running exercise in eight healthy volunteers. A significant (P less than 0.01) increase of the lymphocytic beta-adrenoceptor density from 45 +/- 4 to 81 +/- 9 fmol mg-1 protein (mean +/- SEM) took place during the first hour of exercise. As the exercise was continued for up to 2.1-3 h, the receptor densities did not change significantly any more and remained elevated (72 +/- 9 fmol mg-1 protein) in comparison to the resting levels (P less than 0.02). The isoproterenol-stimulated cAMP production of the lymphocytes increased during the first hour of running from 190 +/- 36 to 269 +/- 56 pmol mg-1 protein (P less than 0.01) and returned to the resting level at the end of the exercise (182 +/- 38 pmol mg-1 protein). The mean levels of plasma catecholamines increased approximately sixfold during the first hour of exercise and remained elevated until the end of the running. This study demonstrates that the beta-adrenergic receptor system is activated in lymphocytes during prolonged aerobic physical exercise. This activated state becomes, however, attenuated within 2-3 h of exercise as indicated by a diminishing ability of beta-adrenoceptors to mediate catecholamine-induced cAMP production.
 ...
PMID:Density and functioning of human lymphocytic beta-adrenergic receptors during prolonged physical exercise. 255 Nov 29

Extracellular ATP has vasodilatory and inotropic effects in the heart. We have demonstrated that extracellular ATP, in a concentration-dependent manner (10 nM-0.1 mM), increased [Ca2+]i in suspensions of isolated fura-2-loaded rat cardiac ventricular myocytes (maximum 96 +/- 10% increase over basal levels, SEM, n = 12, P less than 0.01). The increase in [Ca2+]i was often biphasic, with an initial fast phase (less than 1 s) of low amplitude, followed by a slower phase of higher amplitude. A second application of ATP had little effect, and ATP abolished the effect of subsequent electrical stimulations, even through the cells were still able to respond with an increase in [Ca2+]i to KCl-induced depolarization or stimulation by caffeine. Pretreatment of cells with nifedipine, verapamil, caffeine, ryanodine, or 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride attenuated the effect of extracellular ATP on [Ca2+]i, and binding of extracellular free calcium by excess EGTA completely abolished the effects of extracellular ATP and electrical stimulation. Extracellular ATP increased bisoxonol fluorescence in ventricular myocytes, indicating depolarization of the sarcolemma. Pretreatment of the myocytes with tetrodotoxin (50 microM), or replacement of NaCl in the incubation buffer with the impermeant cation N-methyl-D-glucamine, suppressed the extracellular ATP effect on [Ca2+]i. ADP and AMP had smaller effects on [Ca2+]i than ATP; adenosine had no effect. ATP analogues showed the following rank order of potency in increasing [Ca2+]i or bisoxonol fluorescence: ATP greater than or equal to 2-methylthioATP much greater than adenosine 5'-O-[3-thio]triphosphate greater than adenosine 5'-[alpha, beta-methylene]triphosphate approximately adenosine 5'-[beta, gamma-methylene]triphosphate approximately adenosine 5'-[beta, gamma-imino]triphosphate greater than adenosine. These data are consistent with the presence of purinoceptors (P2Y subtype) on the sarcolemma of cardiac ventricular myocytes of the rat, which upon activation lead to depolarization and activation of cation channels of the sarcolemma and flux of extracellular Ca2+ into the cells. This may result in further flux of Ca2+ into the cytosol from intracellular stores. The effects of extracellular ATP on [Ca2+]i in rat cardiac ventricular myocytes may, in part, explain the direct inotropic effects of extracellular ATP on the mammalian heart.
 ...
PMID:Identification of P2Y purinoceptors associated with voltage-activated cation channels in cardiac ventricular myocytes of the rat. 255 12

Human alveolar macrophages obtained by bronchoalveolar lavage were studied with the high specific activity beta-adrenergic ligand [125I]pindolol and found to possess a moderate density of beta-adrenergic receptors. Using macrophage membranes, the receptor density (Bmax) was 42 +/- 9 fmol/mg protein with an apparent equilibrium dissociation constant (Kd) of 44 +/- 9 pM (mean +/- SEM). With intact macrophages, the Bmax = 5,643 +/- 942 sites/cell with Kd = 29 +/- 9 pM. Competition binding studies with subtype-specific antagonists revealed an exclusive population of beta 2-adrenergic receptors. Incubation of intact macrophages with the beta-adrenergic agonist isoproterenol caused a 6-fold increase in intracellular cyclic AMP (cAMP). Prostaglandin E1 and forskolin, which activate adenylate cyclase via different mechanisms, afforded typical marked increases in macrophage cAMP. Saturation binding, competition binding, and cAMP accumulation studies may all be performed from a single sample of about 2 x 10(7) cells, which can be obtained by bronchoalveolar lavage. This should facilitate studies of in vivo regulation of human alveolar macrophage beta-adrenergic receptors with regard to immune function and mediator release, and as a possible reflection of lung parenchymal receptors.
 ...
PMID:Identification and characterization of a homogeneous population of beta 2-adrenergic receptors on human alveolar macrophages. 256 22

The influence of exercise intensity on the accumulation of inosine monophosphate (IMP) in human skeletal muscle has been investigated. Ten men cycled at workloads corresponding to 40%, 75% and 100% of their maximal oxygen uptake (VO2 max). Muscle IMP was below the detection limit (less than 0.01 mmol kg-1 dry wt) at rest and after exercise at 40% of VO2 max, but increased to 0.26 +/- 0.06 (mean +/- SEM) and 3.50 +/- 0.51 mmol kg-1 dry wt after exercise at 75% and 100% of VO2 max respectively. Accumulation of IMP corresponded to a similar decrease in the total adenine nucleotide content. The muscle content of IMP was positively related to lactate and negatively related to phosphocreatine (PCr). IMP was formed in both fibre types, but the IMP content at fatigue was about twice as high in type II fibres as in type I fibres. It was concluded that the IMP content of human skeletal muscle is very low at rest and after low-intensity exercise, but increases after moderate and high-intensity exercise. In contrast to rat muscle, where deamination of AMP predominantly occurs in the fast-twitch muscle fibres, IMP is formed during exercise in both fibre types in human muscle. Accumulation of IMP appears to reflect an imbalance between the rate of utilization and the rate of regeneration of ATP.
 ...
PMID:Formation of inosine monophosphate (IMP) in human skeletal muscle during incremental dynamic exercise. 278 92

Experiments were designed to investigate whether platelet activation is modulated by endothelium-derived relaxant factor (EDRF) which has been shown to induce vascular smooth muscle relaxation by direct stimulation of soluble guanylate cyclase. EDRF was released from cultured bovine endothelial cells, grown on microcarrier beads, by stimulation with thimerosal in the presence of indomethacin. EDRF had no effect on the intracellular free calcium concentration (Cai2+, measured with the fluorescent indicator indo-1) of resting washed human platelets but significantly attenuated the thrombin-induced rise of Cai2+ from 896 +/- 99 (SEM) to 509 +/- 48 nmol/l. EDRF significantly increased platelet cyclic GMP levels from 0.25 +/- 0.04 to 2.5 +/- 0.4 pmol/10(8) platelets and reduced the thrombin-induced aggregation to 23 +/- 3% of control. EDRF had no effect on Cai2+, cyclic GMP or aggregation after a 3 min storage interval, but superoxide dismutase (shown to increase stability of the labile factor) significantly augmented the EDRF effects on Cai2+. The antiaggregatory potency of EDRF was completely abolished in the presence of hemoglobin. The results characterize EDRF as a potent cyclic GMP-dependent antiaggregatory factor which may act synergistically in vivo with the cyclic AMP-dependent inhibitory effect of prostacyclin.
 ...
PMID:Endothelium-derived relaxant factor inhibits platelet activation. 283 May 46

The purpose of this study was to investigate the effects of the intracellular messenger cyclic GMP (cGMP) on sequestration of cytosolic calcium (Ca2+) into the intracellular Ca2+ store (the sarcoplasmic reticulum) of vascular smooth muscle. Using saponin-skinned primary cultures of rat aortic smooth muscle, we investigated the effect of cGMP on 45Ca uptake in monolayers of cells. The intracellular store was loaded with Ca2+ by exposing the skinned cells to a 45Ca-labeled 1-microM free Ca2+-containing solution for varying durations (0-20 minutes). Addition of 10 microM cGMP to six monolayers increased both the initial Ca2+ uptake at 2 minutes (control, 240 +/- 8 pmol Ca2+/10(6) cells; + cGMP 295 +/- 7; mean +/- SEM; n = 6, p less than 0.01) and the final steady-state uptake reached at 20 minutes (control, 0.96 +/- 0.03 nmol Ca2+/10(6) cells; + cGMP 1.12 +/- 0.03, p less than 0.02). This stimulation of uptake was quantitatively similar to that caused by 10 microM cyclic AMP. It occurred at varying ambient cytosolic Ca2+ concentrations (0.1-1.0 microM Ca2+) and was not further enhanced by addition of 10 microM cGMP-dependent protein kinase. The dose-response of stimulation of Ca2+ uptake with cGMP indicated an ED50 of 5 nM cGMP. The release of Ca2+ from the sarcoplasmic reticulum in response to inositol 1,4,5-trisphosphate or caffeine was unaffected by cGMP. We conclude that the relaxation of vascular smooth muscle with cGMP-producing vasodilators is mediated in part by sequestration of cytosolic Ca2+ by the sarcoplasmic reticulum.
 ...
PMID:Cyclic guanosine monophosphate-enhanced sequestration of Ca2+ by sarcoplasmic reticulum in vascular smooth muscle. 283 13

To test the hypothesis that beta-receptors 'up-regulate' during chronic beta-blockade, myocardial beta-receptor density, affinity and functional sensitivity were examined in dogs before and after chronic beta-blockade. Membrane preparations from the left ventricle and right atrium were assayed for beta-receptors in 8 control dogs, and 8 dogs given oral nadolol (4 mg/kg) twice a day for 3 weeks. Beta-receptor density and affinity of membrane fractions were determined using 3H-dihydroalprenolol (0.5-20 nM), and Scatchard analysis. Beta-receptor densities after chronic beta-blockade were 419 +/- 28 (mean +/- SEM) and 436 +/- 47 fmol/mg protein in membranes from the left ventricle and right atrium respectively. These values were not significantly different from the left ventricle (412 +/- 25) or the right atrium (413 +/- 25) in control dogs. Beta-receptor affinities were 5.6 +/- 0.5 nM (left ventricle) and 8.5 +/- 1.1 nM (right atrium) after chronic beta-blockade, and not significantly different from control (6.9 +/- 0.7 nM, ventricle; 11.3 +/- 0.9 nM, atrium). Beta-receptor sensitivity was determined in membrane fractions from the left ventricle by analysis of the dose-response relationship between isoproterenol and the formation of c-AMP (pmol/min/mg protein). The concentration of isoproterenol that resulted in 50% of the maximal response was not significantly altered by chronic beta-blockade. Maximally stimulated adenylate cyclase with Gpp(NH)p or NaF was also unchanged by beta-blockade. These results suggest that in the canine heart, chronic beta-blockade does not lead to 'up-regulation' of beta-receptors nor catecholamine supersensitivity.
 ...
PMID:Effects of chronic beta-blockade on beta-receptors and adenylate cyclase activity in the canine heart. 283 83


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