Metabolomics: The systematic identification and quantitation of all the metabolic products of a cell, tissue, organ, or organism under varying conditions. The METABOLOME of a cell or organism is a dynamic collection of metabolites which represent its net response to current conditions.ArchivesBiological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Directories as Topic: Lists of persons or organizations, systematically arranged, usually in alphabetic or classed order, giving address, affiliations, etc., for individuals, and giving address, officers, functions, and similar data for organizations. (ALA Glossary of Library and Information Science, 1983)PPAR gamma: A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR ALPHA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES. It is a target of THIAZOLIDINEDIONES for control of DIABETES MELLITUS.Peroxisome Proliferator-Activated Receptors: TRANSCRIPTION FACTORS that are activated by ligands and heterodimerize with RETINOID X RECEPTORS and bind to peroxisome proliferator response elements in the promoter regions of target genes.Lysophosphatidylcholines: Derivatives of PHOSPHATIDYLCHOLINES obtained by their partial hydrolysis which removes one of the fatty acid moieties.PPAR alpha: A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Genome: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.Calcium Channels, L-Type: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Databases, Genetic: Databases devoted to knowledge about specific genes and gene products.Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Calcium Channels, N-Type: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.Calcium Channels, T-Type: A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.Large-Conductance Calcium-Activated Potassium Channel alpha Subunits: The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.Mibefradil: A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.Mesenchymal Stromal Cells: Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Mesenchymal Stem Cell Transplantation: Transfer of MESENCHYMAL STEM CELLS between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS).Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Immunomodulation: Alteration of the immune system or of an immune response by agents that activate or suppress its function. This can include IMMUNIZATION or administration of immunomodulatory drugs. Immunomodulation can also encompass non-therapeutic alteration of the immune system effected by endogenous or exogenous substances.Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.Osteoblasts: Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Cell Culture Techniques: Methods for maintaining or growing CELLS in vitro.Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs.Myocytes, Smooth Muscle: Non-striated, elongated, spindle-shaped cells found lining the digestive tract, uterus, and blood vessels. They are derived from specialized myoblasts (MYOBLASTS, SMOOTH MUSCLE).Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.3',5'-Cyclic-AMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.Hypertension, Pulmonary: Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.Cyclic Nucleotide Phosphodiesterases, Type 4: A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.Milrinone: A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Cyclic Nucleotide Phosphodiesterases, Type 3: A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. In addition multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing.LatviaNeuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Bromus: A plant genus of the family POACEAE. The name is similar to Broom or Scotch Broom (CYTISUS) or Butcher's Broom (RUSCUS) or Desert Broom (BACCHARIS) or Spanish Broom (SPARTIUM).Congresses as Topic: Conferences, conventions or formal meetings usually attended by delegates representing a special field of interest.Riluzole: A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.Pharmacopoeias as Topic: Authoritative treatises on drugs and preparations, their description, formulation, analytic composition, physical constants, main chemical properties used in identification, standards for strength, purity, and dosage, chemical tests for determining identity and purity, etc. They are usually published under governmental jurisdiction (e.g., USP, the United States Pharmacopoeia; BP, British Pharmacopoeia; P. Helv., the Swiss Pharmacopoeia). They differ from FORMULARIES in that they are far more complete: formularies tend to be mere listings of formulas and prescriptions.International Cooperation: The interaction of persons or groups of persons representing various nations in the pursuit of a common goal or interest.Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.United States Food and Drug Administration: An agency of the PUBLIC HEALTH SERVICE concerned with the overall planning, promoting, and administering of programs pertaining to maintaining standards of quality of foods, drugs, therapeutic devices, etc.Drug Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug.Fenoterol: An adrenergic beta-2 agonist that is used as a bronchodilator and tocolytic.Kinetics: The rate dynamics in chemical or physical systems.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Biological Transport, Active: The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Mevalonic AcidPolyisoprenyl Phosphates: Phosphoric or pyrophosphoric acid esters of polyisoprenoids.Protein Prenylation: A post-translational modification of proteins by the attachment of an isoprenoid to the C-terminal cysteine residue. The isoprenoids used, farnesyl diphosphate or geranylgeranyl diphosphate, are derived from the same biochemical pathway that produces cholesterol.Adipocytes: Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.Terpenes: A class of compounds composed of repeating 5-carbon units of HEMITERPENES.Alkyl and Aryl Transferases: A somewhat heterogeneous class of enzymes that catalyze the transfer of alkyl or related groups (excluding methyl groups). EC 2.5.Farnesyltranstransferase: An enzyme that catalyzes the synthesis of geranylgeranyl diphosphate from trans, trans-farnesyl diphosphate and isopentenyl diphosphate.Adipogenesis: The differentiation of pre-adipocytes into mature ADIPOCYTES.Dimethylallyltranstransferase: An enzyme that, in the pathway of cholesterol biosynthesis, catalyzes the condensation of isopentenyl pyrophosphate and dimethylallylpyrophosphate to yield pyrophosphate and geranylpyrophosphate. The enzyme then catalyzes the condensation of the latter compound with another molecule of isopentenyl pyrophosphate to yield pyrophosphate and farnesylpyrophosphate. EC
(1/1387) Luteinizing hormone inhibits conversion of pregnenolone to progesterone in luteal cells from rats on day 19 of pregnancy.

We have previously reported that intrabursal ovarian administration of LH at the end of pregnancy in rats induces a decrease in luteal progesterone (P4) synthesis and an increase in P4 metabolism. However, whether this local luteolytic effect of LH is exerted directly on luteal cells or on other structures, such as follicular or stromal cells, to modify luteal function is unknown. The aim of the present study was to determine the effect of LH on isolated luteal cells obtained on Day 19 of pregnancy. Incubation of luteal cells with 1, 10, 100, or 1000 ng/ml of ovine LH (oLH) for 6 h did not modify basal P4 production. The addition to the culture medium of 22(R)-hydroxycholesterol (22R-HC, 10 microgram/ml), a membrane-permeable P4 precursor, or pregnenolone (10(-2) microM) induced a significant increase in P4 accumulation in the medium in relation to the control value. When luteal cells were preincubated for 2 h with oLH, a significant (p < 0.01) reduction in the 22R-HC- or pregnenolone-stimulated P4 accumulation was observed. Incubation of luteal cells with dibutyryl cAMP (1 mM, a cAMP analogue) plus isobutylmethylxanthine (1 mM, a phosphodiesterase inhibitor) also inhibited pregnenolone-stimulated P4 accumulation. Incubation with an inositol triphosphate synthesis inhibitor, neomycin (1 mM), or an inhibitor of intracellular Ca2+ mobilization, (8,9-N, N-diethylamino)octyl-3,4,5-trimethoxybenzoate (1 mM), did not prevent the decrease in pregnenolone-stimulated P4 secretion induced by oLH. It was concluded that the luteolytic action of LH in late pregnancy is due, at least in part, to a direct action on the luteal cells and that an increase in intracellular cAMP level might mediate this effect.  (+info)

(2/1387) Phosphorylation of the small heat shock-related protein, HSP20, in vascular smooth muscles is associated with changes in the macromolecular associations of HSP20.

Cyclic nucleotide-dependent vasorelaxation is associated with increases in the phosphorylation of a small heat shock-related protein, HSP20. We hypothesized that phosphorylation of HSP20 in vascular smooth muscles is associated with alterations in the macromolecular associations of HSP20. Treatment of bovine carotid artery smooth muscles with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and the adenylate cyclase activator, forskolin, led to increases in the phosphorylation of HSP20 and dissociation of macromolecular aggregates of HSP20. However, 3-isobutyl-1-methylxanthine and forskolin treatment of a muscle that is uniquely refractory to cyclic nucleotide-dependent vasorelaxation, human umbilical artery smooth muscle, did not result in increases in the phosphorylation of HSP20 or to dissociation of macromolecular aggregates. HSP20 can be phosphorylated in vitro by the catalytic subunit of cAMP-dependent protein kinase (PKA) in both carotid and umbilical arteries and this phosphorylation of HSP20 is associated with dissociation of macromolecular aggregates of HSP20. Activation of cyclic nucleotide-dependent signaling pathways does not lead to changes in the macromolecular associations of another small heat shock protein, HSP27. Interestingly, the myosin light chains (MLC20) are in similar fractions as the HSP20, and phosphorylation of HSP20 is associated with changes in the macromolecular associations of MLC20. These data suggest that increases in the phosphorylation of HSP20 are associated with changes in the macromolecular associations of HSP20. HSP20 may regulate vasorelaxation through a direct interaction with specific contractile regulatory proteins.  (+info)

(3/1387) Identification of a region of the C-terminal domain involved in short-term desensitization of the prostaglandin EP4 receptor.

1. The prostaglandin EP4 receptor, which couples to stimulation of adenylyl cyclase, undergoes rapid agonist-induced desensitization when expressed in CHO-K1 cells. 2. Truncation of the 488-amino acid receptor at residue 350 removes the carboxy-terminal domain and abolishes desensitization. 3. To further delineate residues involved in desensitization, the receptor was truncated at position 408, 383 or 369. Receptors truncated at position 408 or 383 underwent PGE2-induced desensitization, whereas the receptor truncated at position 369 displayed sustained activity, indicating that the essential residues for desensitization lie between 370 and 383. 4. The six serines in the 14-amino acid segment between residues 370 and 383 were mutated to alanine, retaining the entire C-terminal domain. Desensitization was absent in cells expressing this mutant. 5. The results indicate involvement of serines located between 370 and 382 in rapid desensitization of the EP4 receptor.  (+info)

(4/1387) Melatonin inhibits release of luteinizing hormone (LH) via decrease of [Ca2+]i and cyclic AMP.

The role of [Ca2+]i and cAMP in transduction of the melatonin inhibitory effect on GnRH-induced LH release from neonatal rat gonadotrophs has been studied, because melatonin inhibits the increase of both intracellular messengers. Treatments increasing Ca2+ influx (S(-) Bay K8644 or KCI) or cAMP concentration (8-bromo-cAMP or 3-isobutyl-1-methylxanthine) potentiated the GnRH-induced LH release and partially diminished the inhibitory effect of melatonin. Combination of the treatments increasing cAMP and calcium concentrations blocked completely the melatonin inhibition of LH release. The combined treatment with 8-bromo-cAMP and S(-) Bay K8644 also blocked the melatonin inhibition of GnRH-induced [Ca2+]i increase in 89 % of the gonadotrophs, while any of the treatments alone blocked the melatonin effect in about 25 % of these cells. These observations suggest that a cAMP-dependent pathway is involved in regulation of Ca2+ influx by melatonin and melatonin inhibition of LH release may be mediated by the decrease of both messengers.  (+info)

(5/1387) Modulation of human airway smooth muscle proliferation by type 3 phosphodiesterase inhibition.

Elevation in cell cAMP content can inhibit mitogenic signaling in cultured human airway smooth muscle (HASM) cells. We studied the effects of the type 3-selective phosphodiesterase inhibitor siguazodan, the type 4-selective phosphodiesterase inhibitor rolipram, and the nonselective inhibitor 3-isobutyl-1-methylxanthine (IBMX) on proliferation of cultured HASM cells. At concentrations selective for the type 3 phosphodiesterase isoform, siguazodan inhibited both [3H]thymidine incorporation (IC50 2 microM) and the increase in cell number (10 microM; 64% reduction) induced by platelet-derived growth factor-BB (20 ng/ml). These effects were mimicked by IBMX. At concentrations selective for type 4 phosphodiesterase inhibition, rolipram was without effect. A 20-min exposure to siguazodan and rolipram did not increase whole cell cAMP levels. However, in HASM cells transfected with a cAMP-responsive luciferase reporter (p6CRE/Luc), increases in cAMP-driven luciferase expression were seen with siguazodan (3.9-fold) and IBMX (16.5-fold). These data suggest that inhibition of the type 3 phosphodiesterase isoform present in airway smooth muscle results in inhibition of mitogenic signaling, possibly through an increase in cAMP-driven gene expression.  (+info)

(6/1387) Isoforms of the Na-K-2Cl cotransporter in murine TAL II. Functional characterization and activation by cAMP.

The functional properties of alternatively spliced isoforms of the mouse apical Na+-K+-2Cl- cotransporter (mBSC1) were examined, using expression in Xenopus oocytes and measurement of 22Na+ or 86Rb+ uptake. A total of six isoforms, generated by the combinatorial association of three 5' exon cassettes (A, B, and F) with two alternative 3' ends, are expressed in mouse thick ascending limb (TAL) [see companion article, D. B. Mount, A. Baekgaard, A. E. Hall, C. Plata, J. Xu, D. R. Beier, G. Gamba, and S. C. Hebert. Am. J. Physiol. 276 (Renal Physiol. 45): F347-F358, 1999]. The two 3' ends predict COOH-terminal cytoplasmic domains of 129 amino acids (the C4 COOH terminus) and 457 amino acids (the C9 terminus). The three C9 isoforms (mBSC1-A9/F9/B9) all express Na+-K+-2Cl- cotransport activity, whereas C4 isoforms are nonfunctional in Xenopus oocytes. Activation or inhibition of protein kinase A (PKA) does not affect the activity of the C9 isoforms. The coinjection of mBSC1-A4 with mBSC1-F9 reduces tracer uptake, compared with mBSC1-F9 alone, an effect of C4 isoforms that is partially reversed by the addition of cAMP-IBMX to the uptake medium. The inhibitory effect of C4 isoforms is a dose-dependent function of the alternatively spliced COOH terminus. Isoforms with a C4 COOH terminus thus exert a dominant negative effect on Na+-K+-2Cl- cotransport, a property that is reversed by the activation of PKA. This interaction between coexpressed COOH-terminal isoforms of mBSC1 may account for the regulation of Na+-K+-2Cl- cotransport in the mouse TAL by hormones that generate cAMP.  (+info)

(7/1387) Insulin-secreting activity of the traditional antidiabetic plant Viscum album (mistletoe).

Viscum album (mistletoe) has been documented as a traditional treatment of diabetes. In acute 20-min tests, 1-10 mg/ml aqueous extract of mistletoe evoked a stepwise 1.1- to 12.2-fold stimulation of insulin secretion from clonal pancreatic B-cells. This effect was abolished by 0.5 mM diazoxide and prior exposure to extract did not alter subsequent stimulation of insulin secretion induced by 10 mM L-alanine, thereby negating a detrimental effect on cell viability. The insulin-releasing effect of mistletoe extract was unaltered by 16.7 mM glucose, l-alanine (10 mM), 3-isobutyl-1-methylxanthine (IBMX) (1 mM), or a depolarising concentration of KCl (25 mM). The ability of extract to enhance insulin secretion did not depend upon the use of heat during extract preparation and was not mediated by lectins. These results demonstrate the presence of insulin-releasing natural product(s) in Viscum album which may contribute to the reported antidiabetic property of the plant.  (+info)

(8/1387) Aldosterone, not estradiol, is the physiological agonist for rapid increases in cAMP in vascular smooth muscle cells.

BACKGROUND: Steroid-induced gene regulation in the endocrine tissues and vascular wall is achieved through the interaction of specific receptor proteins and promoters of target genes. In addition to these delayed steroid actions, rapid effects of steroids have been reported in various tissues that were clearly incompatible with the classic theory of genomic steroid action. METHODS AND RESULTS: Because high doses of 17beta-estradiol have been shown to modulate intracellular cAMP levels in vascular smooth muscle cells, steroid-induced stimulation of adenylate cyclase stimulation and phosphorylation of cAMP response element binding protein was investigated in porcine coronary artery vascular smooth muscle cells. Aldosterone induces a approximately 1.5- to 2.5-fold increase in intracellular cAMP levels (EC50 approximately 0.01 to 0.1 nmol/L) within 1 minute, whereas 17beta-estradiol and hydrocortisone act only at supraphysiological concentrations (10 micromol/L). Aldosterone-induced changes in intracellular cAMP are calcium dependent; they are not blocked by inhibitors of mineralocorticoid receptors, transcription, or protein synthesis. In addition, aldosterone induces a time-dependent phosphorylation of cAMP response element binding protein with potential transcriptional importance. CONCLUSIONS: A nongenomic modulation of vascular smooth muscle cells by aldosterone is consistent with the data that aldosterone, not estrogen, is the physiological stimulus for cAMP.  (+info)

*  Muse cell
34 (1): 160-73. doi:10.1002/stem.2206. PMID 26388204. Fisch, S.C., Gimeno, M.L., Phan, J.D. et al. (2017). Pluripotent ... 34 (1): 160-73. doi:10.1002/stem.2206. PMID 26388204. Kinoshita, K.; Kuno, S.; Ishimine, H.; Aoi, N.; Mineda, K.; Kato, H.; Doi ... Needless to inform that the positive SSEA-3 cells or Muse cells are fresh for maximum one day after sorting and if you sort the ... Cell isolation by SSEA-3 cell sorting can be done using SSEA-3 antibody. Their size is 13~15 μm in diameter. Muse cells do not ...
*  List of MeSH codes (D03)
... methyl ester MeSH D03.383.725.547.950 --- xanthinol niacinate MeSH D03.383.725.565 --- nicotinyl alcohol MeSH D03.383.725.592 ... 4-dichloro-n-methyl-n-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-isomer MeSH D03.383.773.342 --- glycopyrrolate ... methyl ester MeSH D03.383.725.210 --- dimethindene MeSH D03.383.725.220 --- 2,2'-dipyridyl MeSH D03.383.725.227 --- ... 4-methyl-1-homopiperazinylthiocarbonyl)disulfide MeSH D03.383.129.308.100 --- 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone ...
Development of a Cyclic Peptide Inhibitor of the p6/UEV Protein-Protein Interaction.  Development of a Cyclic Peptide Inhibitor of the p6/UEV Protein-Protein Interaction.
Inosine cyclic 3',5'-(hydrogen phosphate). An inosine nucleotide which acts as a mild inhibitor of the hydrolysis of cyclic AMP ... 1-methyl-3-isobutylxanthine. A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases ...
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A micro-radioimmunoassay for the measurement of intracellular cAMP.  A micro-radioimmunoassay for the measurement of intracellular cAMP.
1-Methyl-3-isobutylxanthine / pharmacology. Cholera Toxin / pharmacology. Cyclic AMP / analysis*. Humans. Lymphoma, B-Cell / ... Previous Document: Selective in vitro expansion of HLA class I-restricted HIV-1 Gag-specific CD8+ T cells: cytotoxic T-.... ...
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Lipidomics of cellular and secreted phospholipids from differentiated human fetal type II alveolar epithelial cells.  Lipidomics of cellular and secreted phospholipids from differentiated human fetal type II alveolar epithelial cells.
1-Methyl-3-isobutylxanthine / pharmacology. 8-Bromo Cyclic Adenosine Monophosphate / metabolism. Cell Differentiation. Cells, ... 9613677 - Interleukin-8 and monocyte chemotactic protein-1 production by a human glioblastoma cel.... ... 1). Mixtures of these PC molecular species, phosphatidylglycerol, and SP-B and SP-C were functionally active and rapidly ... 28822-58-4/1-Methyl-3-isobutylxanthine; 50-02-2/Dexamethasone From MEDLINE®/PubMed®, a database of the U.S. National Library of ...
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Neuromodulator-mediated phosphorylation of specific proteins in a neurotumor hybrid cell line (NCB-20). | CureHunter  Neuromodulator-mediated phosphorylation of specific proteins in a neurotumor hybrid cell line (NCB-20). | CureHunter
Neuromodulator-mediated phosphorylation of specific proteins in a neurotumor hybrid cell line (NCB-20). - E Berry-Kravis, B I Kazmierczak, V Derechin, G Dawson
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Two-electrode recordings allow pharmacological manipula | Open-i  Two-electrode recordings allow pharmacological manipula | Open-i
Two-electrode recordings allow pharmacological manipulation of cone phototransductiona. Phototransduction cascade. Light-activated Opsin activates transducin (G
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Metabolomics reveal 1-palmitoyl lysophosphatidylcholine production by peroxisome proliferator-activated receptor α  Metabolomics reveal 1-palmitoyl lysophosphatidylcholine production by peroxisome proliferator-activated receptor α
3. Kahn B. B., Flier J. S. 2000. Obesity and insulin resistance. J. Clin. Invest. 106: 473-481. [PMC free article] [PubMed] ... 1. Reilly M. P., Rader D. J. 2003. The metabolic syndrome: more than the sum of its parts? Circulation. 108: 1546-1551. [PubMed ... 1.. High plasma LPC(16:0) levels in mice activated with PPARα. A: Metabolome analysis of mice plasma treated with bezafibrate ... 3.. High LPC(16:0) levels in murine primary hepatocytes and culture medium treated with PPARα activator, and the secretion of ...
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Muse cell - Wikipedia  Muse cell - Wikipedia
34 (1): 160-73. doi:10.1002/stem.2206. PMID 26388204. Fisch, S.C., Gimeno, M.L., Phan, J.D. et al. (2017). Pluripotent ... 34 (1): 160-73. doi:10.1002/stem.2206. PMID 26388204. Kinoshita, K.; Kuno, S.; Ishimine, H.; Aoi, N.; Mineda, K.; Kato, H.; Doi ... Needless to inform that the positive SSEA-3 cells or Muse cells are fresh for maximum one day after sorting and if you sort the ... Cell isolation by SSEA-3 cell sorting can be done using SSEA-3 antibody. Their size is 13~15 μm in diameter. Muse cells do not ...
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Human immunodeficiency virus replication: Modulation by cellular levels of cAMP<...  Human immunodeficiency virus replication: Modulation by cellular levels of cAMP<...
Forskolin (FK, an activator of adenylate cyclase 1-100 μM), Isobutylmethylxanthene (IBMX, a phosphodiesterase inhibitor, which ... Forskolin (FK, an activator of adenylate cyclase 1-100 μM), Isobutylmethylxanthene (IBMX, a phosphodiesterase inhibitor, which ... Forskolin (FK, an activator of adenylate cyclase 1-100 μM), Isobutylmethylxanthene (IBMX, a phosphodiesterase inhibitor, which ... Forskolin (FK, an activator of adenylate cyclase 1-100 μM), Isobutylmethylxanthene (IBMX, a phosphodiesterase inhibitor, which ...
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Cacna1i (calcium channel, voltage-dependent, alpha 1I subunit) - Rat Genome Database  Cacna1i (calcium channel, voltage-dependent, alpha 1I subunit) - Rat Genome Database
pain 1 (mouse). Not determined. 15. 75448997. 90928982. Mouse. 1301860. Gct3_m. granulosa cell tumorigenesis 3 (mouse). Not ... hepatic fibrogenesis 1 (mouse). Not determined. 15. 47434485. 81434630. Mouse. 1357756. Alaa4_m. alopecia areata 4 (mouse). Not ... Orthologs 1. Homo sapiens (human):. CACNA1I (calcium voltage-gated channel subunit alpha1 I). HGNC. EggNOG, Ensembl, HGNC, ... weight 3 weeks QTL 6 (mouse). Not determined. 78716903. 102993272. Mouse. 10755515. Amzn3_m. anatomical modifier of Zfp423 3 ( ...
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CACNA1I (calcium voltage-gated channel subunit alpha1 I) - Rat Genome Database  CACNA1I (calcium voltage-gated channel subunit alpha1 I) - Rat Genome Database
3.. Pipeline to import KEGG annotations from KEGG into RGD. 4.. RGD automated import pipeline for ClinVar variants, variant-to- ... Orthologs 1. Mus musculus (house mouse):. Cacna1i (calcium channel, voltage-dependent, alpha 1I subunit). HGNC. EggNOG, Ensembl ... 3-isobutyl-1-methyl-7H-xanthine multiple interactions. ISO. RGD:68944. 6480464. Mibefradil inhibits the reaction [[Colforsin co ... 1.. Catterall WA Cold Spring Harb Perspect Biol. 2011 Aug 1;3(8):a003947. doi: 10.1101/cshperspect.a003947.. ...
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Human versus porcine mesenchymal stromal cells: phenotype, differentiation potential, immunomodulation and cardiac improvement...  Human versus porcine mesenchymal stromal cells: phenotype, differentiation potential, immunomodulation and cardiac improvement...
3. J. S. McDaniel, B. Antebi, M. Pilia, B. J. Hurtgen, S. Belenkiy, C. Necsoiu, L. C. Cancio, C. R. Rathbone, A. I. Batchinsky ... 1. Segers VF, Lee RT. Stem-cell therapy for cardiac disease. Nature. 2008; 451: 937-42.. *CrossRef , ... 3. Chen SL, Fang WW, Ye F, et al . Effect on left ventricular function of intracoronary transplantation of autologous bone ... 1 χ 106 per BM sample and 1 χ 104 cells per MSC culture were measured within a 'live cell' gate based on light scatter ...
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Catecholamine-induced release of the folic acid analogue, Methotrexate, from rat hepatocytes in suspension. An alpha-adrenergic...  Catecholamine-induced release of the folic acid analogue, Methotrexate, from rat hepatocytes in suspension. An alpha-adrenergic...
This net efflux of methotrexate induced by epinephrine is markedly potentiated by 3-isobutyl-1-methylxanthine at concentrations ... This net efflux of methotrexate induced by epinephrine is markedly potentiated by 3-isobutyl-1-methylxanthine at concentrations ... This net efflux of methotrexate induced by epinephrine is markedly potentiated by 3-isobutyl-1-methylxanthine at concentrations ... This net efflux of methotrexate induced by epinephrine is markedly potentiated by 3-isobutyl-1-methylxanthine at concentrations ...
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Original Research: Role of phosphodiesterases in modulation of BK
                       ...  Original Research: Role of phosphodiesterases in modulation of BK <sub>Ca</sub> ...
Y1 - 2008/1/1. N2 - BK Ca channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BK Ca channels, ... 3, 01.01.2008, p. 119-127.. Research output: Contribution to journal › Article ... Therapeutic Advances in Respiratory Disease, 2(3), 119-127. ...
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Publikācijas - Latvijas Organiskās sintēzes institūts  Publikācijas - Latvijas Organiskās sintēzes institūts
Toxicol.: Vol.80, Supp.1, 1997; 31. 52. Kluša V.; Ģērmane S.; Duburs G. Taurine and tauropyrone: anti-neurodeficit activity in ... Toxicol.: Vol.80, Supp.1, 1997; 29. 53. Ģērmane S.; Dirnēns V.; Pokrovska N.; Lukevics E. Novel antiamnestic compounds in the ... Toxicol.: Vol.80, Supp.1, 1997; 23. 54. Duburs G.; Kluša V.; Bisenieks E.; Poikāns J. Amino acid-containing derivatives as ... Toxicol.: Vol.80, Supp.1, 1997; 17. 56. Polevaya L.; Matsoukas J.; Vlahakos D.; Mutule I.; Mutule I. Angiotensin-like fragments ...
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DI-fusion Monocyte chemoattractant protein-1 is expressed in pancreatic...  DI-fusion Monocyte chemoattractant protein-1 is expressed in pancreatic...
Monocyte chemoattractant protein-1 is expressed in pancreatic islets from prediabetic NOD mice and in interleukin-1 beta- ... Monocyte chemoattractant protein-1 is expressed in pancreatic islets from prediabetic NOD mice and in interleukin-1 beta- ...
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AJOU Open Repository: Browsing DSpace  AJOU Open Repository: Browsing DSpace
1 2',5'-Oligoadenylate Synthetase/blood * 1 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/analogs & derivatives/* ... 1 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ...
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Icariin Intervenes in Cardiac Inflammaging through Upregulation of SIRT6 Enzyme Activity and Inhibition of the NF-Kappa B...  Icariin Intervenes in Cardiac Inflammaging through Upregulation of SIRT6 Enzyme Activity and Inhibition of the NF-Kappa B...
Yang Chen,1 Tao Sun,2 Junzhen Wu,2 Bill Kalionis,3 Changcheng Zhang,4 Ding Yuan,4 Jianhua Huang,5 Waijiao Cai,5 Hong Fang,6 and ... 3.4.1. The Effect of ICA on SIRT6 and NF-κB (p65) Protein Expression in Each Group of Aortic ECs. Figure 5(a) shows that after ... In Figure 6(b) after addition of TNF-α, mRNA levels of NF-κB (p65) downstream inflammatory cytokines (TNF-α, ICAM-1, IL-2, and ... 3.4.3. Qualitative Assessment of the Effect of ICA on NF-κB (p65) Nuclear Translocation. NF-κB (p65) is normally present in the ...
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Fibroblast Growth Factor 1 | Diabetes  Fibroblast Growth Factor 1 | Diabetes
Fibroblast Growth Factor 1. Louise Hutley, Wenda Shurety, Felicity Newell, Ross McGeary, Nicole Pelton, Jennifer Grant, Adrian ... Fibroblast Growth Factor 1. Louise Hutley, Wenda Shurety, Felicity Newell, Ross McGeary, Nicole Pelton, Jennifer Grant, Adrian ... 1C; triacylglycerol, Fig. 1D) and omental (G3PDH, Fig. 1E; triacylglycerol, Fig. 1F) adipose tissue depots. While the rise in ... FGF-1). This FGF-1-induced growth is attenuated in the presence of the FGF inhibitors peptide 1 (Pep 1) (10 μg/ml) (n = 6, *P ...
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Academic Dissertations;Academic Dissertations--South Carolina;1-Methyl-3-isobutylxanthine--pharmacology;Receptor, Adenosine A2B ... pharmacology and toxicology of 3-isobutyl 1-methylxanthine (IBMX) in the 661w retina-derived cell line ...
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3-Isobutyl-1-Methyl Xanthine  3-Isobutyl-1-Methyl Xanthine
... non-specific inhibitor of adenosine 3',5'-cyclic monophosphate phosphodiesterase (cAMP PDE)4, significantly more effective than ... resulting in accumulation of cyclic AMP and guanosine 3',5'-cyclic monophosphate. ... 3-Isobutyl-1-Methyl Xanthine. Synonyms IBMX; MIX; MeiBu-Xan; IBX; 1-Methyl-3-isobutylxanthine, 3,7-Dihydro-1-methyl-3-(2- ... Soluble in Krebs-Henseleit bicarbonate buffer, ethanol (10 mg/mL or 25 mg/mL with sonication), DMSO (1 M with warming), or ...
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  • FPP induced the in vitro binding of a co-activator, SRC-1 (steroid receptor co-activator-1), to GST (glutathione transferase)-PPARγ. (
  • Residues in the 17-amino acid disulfide ring of BNP were substituted to modulate receptor-binding affinity ( Fig. 1 ). (
  • Forskolin (FK, an activator of adenylate cyclase 1-100 μM), Isobutylmethylxanthene (IBMX, a phosphodiesterase inhibitor, which indirectly increases intracellular levels of cAMP, 30-100 μM) and dibuteryl (db) cAMP (0.1-10 μM) enhanced HIV replication, in a dose-dependent manner. (
  • IBMX has been shown to be a potent, non-specific inhibitor of adenosine 3',5'-cyclic monophosphate phosphodiesterase (cAMP PDE)4, significantly more effective than theophylline. (
  • 6. IBMX, Org 9935, siguazodan and rolipram (1 - 50 microM), but not zaprinast, each augmented glucose-induced insulin secretion in the presence of 16.7 mM but not 1 mM glucose. (
  • Treatment of differentiated epithelial cells with secretagogues stimulated the secretion of functional surfactant-containing surfactant proteins B and C (SP-B and SP-C). Secreted material was further enriched in this same set of phospholipid species but was characterized by increased contents of short-chain monounsaturated and disaturated species other than dipalmitoyl PC (PC16:0/16:0), principally palmitoylmyristoyl PC (PC16:0/14:0) and palmitoylpalmitoleoyl PC (PC16:0/16:1). (
  • Can be isolated as cells positive for SSEA-3, a well known human embryonic stem cell marker. (
  • Flow cytometric analysis revealed that pMSC expressed surface antigens also found on hMSC, including CD90, MSCA-1 (TNAP/W8B2 antigen), CD44, CD29 and SLA class I. Clonogenic outgrowth was significantly enriched following selection of CD271+ cells from BM of human and pig (129 ± 29 and 1961 ± 485 fold, respectively). (
  • This net efflux of methotrexate induced by epinephrine is markedly potentiated by 3-isobutyl-1-methylxanthine at concentrations which do not, alone, result in net loss of methotrexate from the cells. (
  • We also show that 3T3-L1 cells, a highly efficient murine model of adipogenesis, express FGF-1 and, unlike human preadipocytes, display no increased differentiation potential in response to exogenous FGF-1. (
  • Conversely, FGF-1-treated human preadipocytes proliferate rapidly and differentiate with high efficiency in a manner characteristic of 3T3-L1 cells. (
  • Monocyte chemoattractant protein-1 is expressed in pancreatic islets from prediabetic NOD mice and in interleukin-1 beta-exposed human and rat islet cells. (
  • In vitro anti-inflammatory and anti-adipogenic assays were evaluated against the RAW 264.7 macrophage cells and 3 T3-L1 cells respectively. (
  • During PPARα activation, transcription of PPARα-regulated genes [e.g., carnitine- O -palmitoyltransferase 1 ( CPT1 ) and acyl-CoA oxidase ( ACO )] is stimulated and β-oxidation is activated ( 12 - 14 ). (
  • ICA upregulated the expression of SIRT6 and had an inhibitory effect on NF- κ B inflammatory signaling pathways as shown by decreasing mRNA levels of the NF- κ B downstream target genes TNF- α , ICAM-1, IL-2, and IL-6. (
  • Zhu, S, White, RE & Barman, SA 2008, ' Original Research: Role of phosphodiesterases in modulation of BK Ca channels in hypertensive pulmonary arterial smooth muscle ', Therapeutic Advances in Respiratory Disease , vol. 2, no. 3, pp. 119-127. (
  • 1. The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT - PCR. (
  • 1 Mechanism of Action of Gonadoptropins and the Regulation of Gene Expression. (
  • Intrinsic to the process is the development of the potential to store energy in the form of triglyceride, development of the capacity for insulin-stimulated glucose uptake, and production of characteristic proteins such as glycerol-3-phosphate dehydrogenase (G3PDH) ( 7 ) and leptin ( 8 , 9 ). (
  • DI-fusion Monocyte chemoattractant protein-1 is expressed in pancreatic. (
  • Primary mouse chondrocytes treated with interleukin 1 beta (IL-1β) were used as an in vitro model to evaluate the effects of the conditioned medium with or without exosomes and titrated doses of isolated exosomes for 48 hours, prior to immunocytochemistry or western blot analysis. (
  • 2. Calmodulin activated cyclic AMP or cyclic GMP PDE activity in pellet and was 3 fold (P=0.002) more potent in activating cyclic nucleotide hydrolysis in pellet compared with supernatant fractions. (
  • Expression of FGF-1 was demonstrated in MVECs but not in preadipocytes, while preadipocytes were shown to express FGF receptors 1-4. (
  • SIRT6-deficient mice are small and at 2-3 weeks of age develop abnormalities that include profound lymphopenia, loss of subcutaneous fat, lordokyphosis, and severe metabolic defects. (
  • The pathophysiology of obesity and obesity-associated metabolic disorders including Type 2 diabetes mellitus, hypertension, hyperlipidaemia and cardiovascular disease is associated with abnormalities in endocrine signalling in WAT (white adipose tissue) [ 1 , 2 ]. (
  • We now demonstrate that coculture of human preadipocytes with MVECs significantly increases preadipocyte differentiation, evidenced by dramatically increased triacylglycerol accumulation and glycerol-3-phosphate dehydrogenase activity compared with controls. (
  • 3. The PDE1/PDE5 inhibitor zaprinast inhibited both cyclic AMP and cyclic GMP PDE activity in both pellet and supernatant fractions of cell homogenates by a maximum of around 25% (IC(50) 1 - 5 microM), while rolipram (PDE4 selective) inhibited only cyclic AMP hydrolysis. (
  • IGF-1 (2 - 7.5 ng ml(-1)) potently augmented this PDE activity. (
  • Obesity is recognized to have major adverse health effects and is a risk factor for serious chronic disorders ( 1 - 4 ), including diabetes and cardiovascular diseases. (
  • In the presence of lovastatin, an HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitor, both intracellular FPP levels and PPARγ-target gene expressions were decreased. (
  • We therefore suggest that FGF-1 is a key human adipogenic factor, and these data expand our understanding of human fat tissue growth and have significant potential for development of novel therapeutic strategies in the prevention and management of human obesity. (
  • 3 Structural and lmmunochemical Properties of Human Choriogonadotropin. (
  • Eleven of the 17 residues are identical between human ANP, BNP, and CNP, which leaves only two unique triad sequences as potential regulators of binding specificity ( Fig. 1 ). (
  • Studies in fetal adipose tissue suggest both spatial and temporal relationships between adipogenesis and angiogenesis ( 3 ). (
  • Subsequent analysis identified fibroblast growth factor (FGF)-1 as an adipogenic factor produced by MVECs. (
  • This well-known Chinese herbal medicine has proven efficacy in treating cardiovascular diseases and osteoporosis and in improving sexual and neurological function and is widely used to treat particular age-related diseases in oriental countries [ 1 , 2 ]. (
  • Expansion of adipose tissue in obesity is preceded by the development of new capillaries ( 1 ). (
  • In particular, 1-palmitoyl lysophosphatidylcholine [LPC(16:0)] is increased by bezaf-ibrate treatment in both plasma and liver. (