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1.
Using [3H] diazepam as ligand, it is possible to distinguish neuronal binding sites from those present on glial elements and in peripheral tissues (non-neuronal). The function of the "non-neuronal" binding sites is still obscure. Preliminary data showed a distribution of [3H] diazepam binding sites in kidney that could suggest a localization along the renal tubules. This is the site at which a renal peptide, arginine-vasopressin (AVP) is supposed to act. In an attempt to examine the function of these "non-neuronal" sites, we studied the [3H] diazepam binding in kidney of Brattleboro rats which lack AVP and present the symptoms of diabetes insipidus. The homozygous Brattleboro rats showed an increase in the apparent number of benzodiazepine binding sites (Bmax) compared to Long-Evans control rats. Replacement of AVP in these animals results in a reversal of the electrolyte alterations of diabetes insipidus and in an increase of the affinity of the [3H] diazepam binding. These findings may indicate a possible relationship between benzodiazepine binding sites and vasopressin action in kidney and may support receptor function of these "non-neuronal" binding sites. 相似文献
2.
Jingru Che Thomas J. DePalma Hemamylammal Sivakumar Louisa S. Mezache Miranda M. Tallman Monica Venere Katelyn Swindle-Reilly Rengasayee Veeraraghavan Aleksander Skardal 《Biotechnology and bioengineering》2023,120(4):1108-1119
Glioblastoma (GBM) is the most common form of brain cancer. Even with aggressive treatment, tumor recurrence is almost universal and patient prognosis is poor because many GBM cell subpopulations, especially the mesenchymal and glioma stem cell populations, are resistant to temozolomide (TMZ), the most commonly used chemotherapeutic in GBM. For this reason, there is an urgent need for the development of new therapies that can more effectively treat GBM. Several recent studies have indicated that high expression of connexin 43 (Cx43) in GBM is associated with poor patient outcomes. It has been hypothesized that inhibition of the Cx43 hemichannels could prevent TMZ efflux and sensitize otherwise resistance cells to the treatment. In this study, we use a three-dimensional organoid model of GBM to demonstrate that combinatorial treatment with TMZ and αCT1, a Cx43 mimetic peptide, significantly improves treatment efficacy in certain populations of GBM. Confocal imaging was used to visualize changes in Cx43 expression in response to combinatorial treatment. These results indicate that Cx43 inhibition should be pursued further as an improved treatment for GBM. 相似文献
3.
4.
G Tallman J E Akers B T Burlingham G R Reeck 《Biochemical and biophysical research communications》1977,79(3):815-822
Histone synthesis decreases approximately in parallel with the decrease in cellular DNA synthesis when KB cell monolayers are productively infected with adenovirus type 2 and does not occur in coordination with the later surge of viral DNA synthesis. The synthesis of histones is not, therefore, required for all replicative DNA synthesis in the nuclei of mammalian cells. 相似文献
5.
Alpha-adrenergic receptors on human platelets. 总被引:4,自引:0,他引:4
[3H] dihydroergocyrptine, an α-adrenergic antagonist, binds specifically to sites on human platelet membranes. Prostaglandin E1 (PGE1) stimulates the production of cyclic AMP (cAMP) in human platelets. Alpha-adrenergic agonists, 1-epinephrine and 1-norepinephrine, and antagonists, phentolamine, phenoxybenzamine, and dihydroergocyrptine inhibit the binding of [3H] dihydroergocryptine. The α-adrenergic agonists inhibit PGE1-stimulated cAMP production and the α-adrenergic antagonists phentolamine and dihydroergocryptine reverse this inhibition. The β-adrenergic agonist 1-isoproterenol and the β-adrenergic antagonists d1-propranolol and 1-alprenolol do not significantly alter binding or PGE1-stimulated cAMP production. Clonidine, dopamine, and serotonin inhibit binding, but clonidine and dopamine are weak inhibitors of PGE1-stimulated cAMP production, and serotonin is without effect. Tyramine, an amine without direct adrenergic activity fails to inhibit binding. Alpha-adrenergic agonists decrease the apparent affinity of a PGE1-receptor activating cAMP production. The inhibition of PGE1-stimulated cAMP production is a physiological measure of α-adrenergic agonist binding to the α-receptor. 相似文献
6.
Radioactive gangliosides, N-[14C]-acetylneuraminylgalactosylglucosylceramide ([14C]GM3) and N- [14C]-acetylneuraminylgalactosyl-N-acetylgalactosaminyl- [N-acetylneuraminyl]-galactosylglucosylceramide ([14C]GD1a), were synthesized from CMP-[14C]sialic acid and the appropriate precursor glycolipid using specific sialyltransferase activities. These compounds were isolated and used as substrates to assay sialidase activity in HeLa cells. Although sodium butyrate added to the culture medium increased GM3 biosynthesis in HeLa cells, sialidase activity, as well as that of other glycohydrolases, was the same in control and butyrate-treated HeLa cells. The same sialidase activity appeared to hydrolyze both [14C]GM3 and [14C]GD1a, but not fetuin; the enzyme had a pH optimum of 5.0 and a Km of 75 μm for the ganglioside substrates. Although the cells contained a high sialidase activity (4–7 nmol/mg of protein/h) and could bind exogenously added [14C]GM3, no “ecto”-sialidase activity would be detected in intact cells under conditions where a close to physiological pH is maintained. The results indicate that ganglioside sialidase is not involved directly in the morphological and biochemical differentiation induced in HeLa cells by exposure to sodium butyrate. 相似文献
7.
Synopsis Pearl dace, Semotilus margarita, are common in slow-moving channels and pools of the headwaters of the Brokenhead River. From May to September age groups 0, 1 and 2+ were partially segregated in space based on water depth with age 0 occupying shallow pools and shallow channels. Age 1 were abundant in shallow pools and deep channels while age 2+ occurred in deep channels and deep pools. In November all age groups coexisted in deep pools. Pearl dace are omnivorous consuming invertebrates, plant material, and detritus. From May to September age groups 0 and 1 consumed mainly terrestrial invertebrates (Diptera, Hymenoptera, Thysanoptera) but age 1 consumed more detritus than age 0. Age 2+ consumed mainly aquatic Diptera larvae. Although all ages consumed aquatic insects almost exclusively in November differences in diet between age groups still existed. Younger fish fed higher in the water column than older fish. Intraspecific resource partitioning of food and space occurs between age groups and this combined with the omnivorous diet is highly adaptive to the headwaters of streams. 相似文献
8.
Sarah A. Scott Yun Xiang Thomas P. Mathews Hyekyung P. Cho David S. Myers Michelle D. Armstrong Keri A. Tallman Matthew C. O'Reilly Craig W. Lindsley H. Alex Brown 《The Journal of biological chemistry》2013,288(28):20477-20487
Phosphatidic acid (PA) is a lipid second messenger located at the intersection of several lipid metabolism and cell signaling events including membrane trafficking, survival, and proliferation. Generation of signaling PA has long been primarily attributed to the activation of phospholipase D (PLD). PLD catalyzes the hydrolysis of phosphatidylcholine into PA. A variety of both receptor-tyrosine kinase and G-protein-coupled receptor stimulations have been shown to lead to PLD activation and PA generation. This study focuses on profiling the PA pool upon P2Y6 receptor signaling manipulation to determine the major PA producing enzymes. Here we show that PLD, although highly active, is not responsible for the majority of stable PA being produced upon UDP stimulation of the P2Y6 receptor and that PA levels are tightly regulated. By following PA flux in the cell we show that PLD is involved in an initial increase in PA upon receptor stimulation; however, when PLD is blocked, the cell compensates by increasing PA production from other sources. We further delineate the P2Y6 signaling pathway showing that phospholipase Cβ3 (PLCβ3), PLCδ1, DGKζ and PLD are all downstream of receptor activation. We also show that DGKζ is a novel negative regulator of PLD activity in this system that occurs through an inhibitory mechanism with PKCα. These results further define the downstream events resulting in PA production in the P2Y6 receptor signaling pathway. 相似文献
9.
K M Garrett R S Duman N Saito A J Blume M P Vitek J F Tallman 《Biochemical and biophysical research communications》1988,156(2):1039-1045
A cDNA clone of an alpha subunit of the human GABA-A receptor has been isolated. The human clone (pCLL800) contains 1055 nucleotides in an open reading frame and 260 nucleotides in the 5' non-coding region. The 351 amino acid sequence of this human alpha subunit shows 97% homology with its bovine counterpart. Hybridization of pCLL800 to Northern blots shows a 3.9/4.3 Kb RNA doublet in human cortex, rat whole brain, cortex, hippocampus, midbrain, olfactory bulb and cerebellum. Developmental studies show that the levels of the rat alpha mRNA increase between one and three weeks of age in a manner similar to the development of the benzodiazepine binding sites. 相似文献
10.
Using leaf epidermis from Vicia faba, we tested whether auxin-induced stomatal opening was initiated by auxin-induced ethylene synthesis. Epidermis was dark-incubated in buffered KNO3 containing 0.1 mM alpha-napthalene acetic acid or 1 mM indole-3-acetic acid. Maximum net opening was ca. 4 micron after 6 h. Opening was reversed by 20 microM ABA, 0.1 mM CaCl2. 1-Aminocyclopropane carboxylic acid (ACC) synthase catalyzes synthesis of ACC, the immediate precursor to ethylene. Auxin-induced stomatal opening was fully inhibited by 10 microM 1-aminoethoxyvinylglycine (AVG), an ACC synthase inhibitor. In solutions containing AVG, auxin-induced opening was restored in a concentration-dependent manner by exogenous ACC, but not in control solutions lacking an auxin. ACC-mediated reversal of AVG-inhibition of stomatal opening was inhibited by alpha-aminoisobutyric acid (AIB), an inhibitor of ACC oxidase, the last enzyme in the ethylene biosynthetic pathway, by 10 microM silver thiosulfate (STS), an inhibitor of ethylene action, and by 20 microM ABA, 0.1 mM CaCl2. CoCl2, an inhibitor of ethylene synthesis, also inhibited auxin-induced opening. Both STS and CoCl2 inhibited opening induced by light or by fusicoccin, but neither light- nor fusicoccin-induced opening was inhibited by AVG. These results support the hypothesis that auxin-induced stomatal opening is mediated through auxin-induced ethylene production by guard cells. 相似文献