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71.
72.
Tonic GABAergic inhibition of taste-responsive neurons in the nucleus of the solitary tract 总被引:4,自引:1,他引:3
The effects of gamma-aminobutyric acid (GABA) and the GABAA receptor
antagonist bicuculline methiodide (BICM) on the activity of taste-
responsive neurons in the nucleus of the solitary tract (NST) were examined
electrophysiologically in urethane-anesthetized hamsters. Single neurons in
the NST were recorded extracellularly and drugs (21 nl) were microinjected
into the vicinity of the cell via a multibarrel pipette. The response of
each cell was recorded to lingual stimulation with 0.032 M NaCl, 0.032 M
sucrose, 0.0032 M citric acid and 0.032 M quinine hydrochloride (QHCl).
Forty-six neurons were tested for the effects of GABA; the activity of 29
cells (63%) was inhibited by 5 mM GABA. Whether activity was elicited in
these cells by repetitive anodal current stimulation (25 microA, 0.5 s, 0.1
Hz) of the tongue (n = 13 cells) or the cells were spontaneously active (n
= 13 cells), GABA produced a dose-dependent (1, 2 and 5 mM) decrement in
activity. Forty- seven NST neurons were tested for the effects of BICM on
their responses to chemical stimulation of the tongue; the responses of 28
cells (60%) were enhanced by 10 mM BICM. The gustatory responses of 26 of
these cells were tested with three concentrations (0.2, 2 and 10 mM) of
BICM, which produced a dose-dependent increase in both spontaneous activity
and taste-evoked responses. Nine of these neurons were sucrose- best, seven
were NaCl-best, eight were acid-best and two responded best to QHCl. The
responses to all four tastants were enhanced, with no difference among
neuron types. For 18 cells that were tested with two or more gustatory
stimuli, BICM increased their breadth of responsiveness to their two most
effective stimuli. These data show that approximately 60% of the
taste-responsive neurons in the rostral NST are inhibited by GABA and/or
subject to a tonic inhibitory influence, which is mediated by GABAA
receptors. The modulation of these cells by GABA provides a mechanism by
which the breadth of tuning of the cell can be sharpened. Modulation of
gustatory activity following a number of physiological changes could be
mediated by such a GABAergic circuit.
相似文献
73.
Molecular evolution of the Sex-Ratio inversion complex in Drosophila pseudoobscura: analysis of the Esterase-5 gene region 总被引:2,自引:0,他引:2
The Sex-Ratio chromosome in Drosophila pseudoobscura is subject to meiotic
drive. It is associated with a series of three nonoverlapping paracentric
inversions on the right arm of the X chromosome. The esterase-5 gene region
has been localized to section 23 within the subbasal inversion of the
Sex-Ratio inversion complex, making esterase- 5 a convenient locus for
molecular evolutionary analyses of the Sex- Ratio inversion complex and the
associated drive system. A 504-bp fragment of noncoding, intergenic DNA
from the esterase-5 gene region was amplified and sequenced from 14
Sex-Ratio and 14 Standard X chromosomes of D. pseudoobscura, and from 9 X
chromosomes of its two sibling species, Drosophila persimilis and
Drosophila miranda. There is extensive sequence differentiation between the
Sex-Ratio and Standard chromosomal types. The common Standard chromosome is
highly polymorphic, while, as expected from either the neutral mutation
theory or the selective sweep hypothesis, the rarer Sex-Ratio chromosome
has much less within-chromosome nucleotide polymorphism. We estimate that
the Standard and Sex-Ratio chromosomes in D. pseudoobscura diverged between
700,000 and 1.3 Mya, or at least 2 million generations ago. The clustering
of D. pseudoobscura Sex-Ratio chromosomes in a neighbor- joining phylogeny
indicates a fairly old, monophyletic origin in this species. It appears
from these data that Sex-Ratio genes were present prior to the divergence
of D. pseudoobscura and D. persimilis and that both the Standard and
Sex-Ratio chromosomes of D. persimilis were derived from the Standard
chromosome of D. pseudoobscura after the inversion events that isolated the
D. pseudoobscura Sex-Ratio chromosome.
相似文献
74.
K M Lounsbury P J Casey L F Brass D R Manning 《The Journal of biological chemistry》1991,266(32):22051-22056
We have demonstrated previously that the G protein alpha subunit Gz alpha (or Gx alpha) in human platelets is subject to phosphorylation by agents that activate protein kinase C, including phorbol 12-myristate 13-acetate, thrombin, and the thromboxane A2 analog U46619. We examine here the site and selectivity of phosphorylation both in vitro using recombinant G protein alpha subunits and in situ using permeabilized and intact platelets. Protein kinase C catalyzes the rapid and nearly stoichiometric phosphorylation of recombinant Gz alpha, with the modification occurring preferentially for the GDP-bound form of the subunit. Under the same conditions, phosphorylation of recombinant Gi alpha 1, Gi alpha 2, Gi alpha 3, Gs alpha-S, Gs alpha-L, and Go alpha 1 was minimal. Phosphorylation of both rGz alpha and platelet Gz alpha occurs at a serine residue near the amino terminus. This conclusion is supported by phosphoamino acid analysis and the incorporation of radiolabel from [gamma-32P]ATP into the amino-terminal CNBr peptide (residues 2-53 of the encoded protein). One of the antisera used in this study (6354, directed toward residues 24-33) recognizes only the nonphosphorylated form of Gz alpha, providing strong evidence that Ser25 or Ser27 is the site of phosphorylation. Results obtained with 6354 also suggest that phorbol ester-promoted phosphorylation of Gz alpha approaches 1 mol of phosphate per mol of subunit in permeabilized platelets. 相似文献
75.
Nicole Lounsbury Tess Eidem Jennifer Colquhoun George Mateo Magid Abou-Gharbia Paul M. Dunman Wayne E. Childers 《Bioorganic & medicinal chemistry letters》2018,28(6):1127-1131
We recently discovered RnpA as a promising new drug discovery target for methicillin-resistant S. aureus (MRSA). RnpA is an essential protein that is thought to perform two required cellular processes. As part of the RNA degrasome Rnpa mediates RNA degradation. In combination with rnpB it forms RNase P haloenzymes which are required for tRNA maturation. A high throughput screen identified RNPA2000 as an inhibitor of both RnpA-associated activities that displayed antibacterial activity against clinically relevant strains of S. aureus, including MRSA. Structure-activity studies aimed at improving potency and replacing the potentially metabotoxic furan moiety led to the identification of a number of more potent analogs. Many of these new analogs possessed overt cellular toxicity that precluded their use as antibiotics but two derivatives, including compound 5o, displayed an impressive synergy with mupirocin, an antibiotic used for decolonizing MSRA whose effectiveness has recently been jeopardized by bacterial resistance. Based on our results, compounds like 5o may ultimately find use in resensitizing mupirocin-resistant bacteria to mupirocin. 相似文献
76.
Although it is now apparent that the intracellular pH may rise considerably above neutrality under physiological conditions, information on the effect of alkaline pH on microtubule assembly and disassembly is still quite fragmentay. We have studied the assembly/disassembly of bovine brain microtubule protein at alkaline pH in vitro. When microtubules are assembled to a new steady state at pH less than 7 and pH is then made more alkaline, they undergo a rapid disassembly to a new steady state. This disassembly is reversed by acidification. The degree of disassembly is determined largely by the pH- dependence of the critical concentration, which increases five to eight times, from pH 7 to 8. A fraction of assembly-incompetent tubulin is identified that increases with pH, but its incompetency is largely reversed with acidification. Measurements of microtubule lengths are used to indicate that disassembly occurs by uniform shortening of microtubules. A comparison of shortening by alkalinization with dilution suggests that the intrinsic rate of disassembly is accelerated by increasing pH. The capacity for initiating assembly is progressively lost with incubation at alkaline pH (although some protection is afforded by sulfhydryl-reducing agents). However, direct assembly from depolymerized mixtures is possible at least up to pH 8.3, and the steady state achieved at these alkaline pH values is stable. Such preparations are readily disassembled by cold and podophyllotoxin (PLN). Disassembly induced by PLN is also markedly enhanced at alkaline pH, suggesting a corresponding enhancement of “treadmilling.” The implications of physiological events leading to alkaline shifts of pH for microtubule assembly/disassembly are discussed, particularly in the light of recent hypotheses regarding treadmilling and its role in controlling the distribution of microtubules in vivo. 相似文献
77.
Karina Ckless Niki L Reynaert Douglas J Taatjes Karen M Lounsbury Albert van der Vliet Yvonne Janssen-Heininger 《Nitric oxide》2004,11(3):216-227
The formation of S-nitrosylated proteins is a nitric oxide-dependent post-translational modification important in signal transduction, yet the in situ detection of S-nitrosylated proteins remains problematic. In this study, we adapted a recently developed biotin derivatization approach to visualize S-nitrosylated proteins in intact cells. This strategy circumvents the use of antibodies directed against S-nitrosocysteine, which may have problematic specificity, due to epitope instability. Endogenous protein S-nitrosylation could be observed in intact cells and in mouse lung sections using fluorophore-conjugated streptavidin and confocal microscopy, and was enhanced by S-nitrosothiols and reduced following treatment with the nitric oxide synthase inhibitor, L-N-monomethyl arginine. Intriguingly, protein S-nitrosylation was detected mainly in the nuclear compartment of cells under baseline conditions and was enhanced when nuclear export was blocked with leptomycin B. We also determined that the small GTPase Ran, a key regulator of nucleocytoplasmic transport, is a target for S-nitrosylation. These findings demonstrate that biotin derivatization is a useful approach to detect S-nitrosylated proteins in situ in cellular compartments or tissues, and will be useful in the assessment of altered S-nitrosylation in pathological conditions. 相似文献
78.
Intercontinental distribution of Plagiochila corrugata (Plagiochilaceae, Hepaticae) inferred from nrDNA ITS sequences and morphology 总被引:1,自引:0,他引:1
JOCHEN HEINRICHS HENK GROTH MELANIE LINDNER CARSTEN RENKER TAMÁS PÓCS THOMAS PRÖSCHOLD 《Botanical journal of the Linnean Society. Linnean Society of London》2004,146(4):469-481
Plagiochila sect. Vagae is a large pantropical clade that is characterized morphologically by frequent terminal branching, vegetative distribution by propagules on the ventral surface of the leaves and a capsule wall with thickenings in all layers. Plagiochila corrugata from Brazil is characterized by strongly undulate, toothed leaf margins and represents the only known neotropical species of sect. Vagae with unispiral elaters. Plagiochila cambuena from Madagascar is distinguished by the same features. Maximum likelihood and parsimony analyses of 38 nrDNA ITS sequences of Plagiochila reveal P. corrugata and P. cambuena in a weakly (ML) to well (MP) supported monophyletic lineage within P. sect. Vagae . As an outcome of the morphological and molecular investigation, P. cambuena is relegated to the synonymy of P. corrugata. Plagiochila corrugata is placed in a Vagae -subclade with 11 further American species. The range of P. corrugata can be ascribed to long-range dispersal from the Neotropics rather than a Gondwanan distribution. Species from tropical Asia and Africa are placed at the base of the Vagae clade. Branch length within P. sect. Vagae points to a sudden radiation. © 2004 The Linnean Society of London, Botanical Journal of the Linnean Society , 2004, 146 , 469–481. 相似文献
79.
Previously we described lectin-like molecules in the ciliate Tetrahymena pyriformis; by application of synthetic neoglycoconjugates it is now shown that T. pyriformis contains considerable amounts of both a β-d-glucose- and a lactose-specific lectin. No evidence for the presence of α-d-mannose-, α-d-galactose- or of α-l-fucose-specific lectins could be obtained. The two lectins, identified in T. pyriformis, are associated with the kinetids. During cell division the lectins disappear or become masked in the fission furrow. Therefore, we assume that these lectins are involved in the organization of the distribution pattern of the kinetids during cell division perhaps due to lectin—glycoprotein interactions. 相似文献
80.
Bin Jiang Jeffrey Mason Anahid Jewett William CS Cho Yan-gao Man 《International journal of biological sciences》2012,8(8):1206-1216
Background: A great number of in vitro and in vivo studies have suggested that many pathways or factors can stimulate angiogenesis and lymphangiogenesis, which facilitate tumor progression and metastasis. However, the morphological and immunohistochemical profile of newly formed vasculatures has not been elucidated, making it difficult to differentiate them from the pre-existing ones, and to identify their unique molecular profiles for diagnosis and therapeutic interventions.Experimental findings: As cytokeratin (CK)-19 is a well-recognized stem cell marker and CK-19-positive cells are frequently detected in the peripheral blood of patients with metastatic cancer, our recent studies have assessed the involvement of CK-19 in the formation of new vasculatures in primary colorectal cancer (CRC) tissues. Our studies showed that a subset of lymph node-positive cases harbored some isolated normal epithelial structures with distinct CK-19 immunostaining within an otherwise CK-19-negative background. These structures are exclusively located within or adjacent to lymphoid follicles and are often surrounded by tube-like structures expressing lymphatic endothelial marker D2-40. Similar structures are more frequently seen at the junctions between pre-invasive and invasive CRC with the following features: (1). they consist of a single layer of endothelial cells that express both D2-40 and CD34, (2). their endothelial walls are often incomplete with disseminated cells protruding into the adjacent stroma, and (3). they are exclusively associated with disseminated CK-19-positive cellsHypothesis: Based on these findings, we propose that these tube-like structures represent newly formed vasculatures, which are derived by the convergence of aberrant lymphocyte infiltration and tumor stem cells. Because of their close physical proximity, tumor stem cells within the epithelial and stromal components contribute equally and coordinately to the morphogenesis of new vasculatures, which constitutes the basis for the unique morphologic and immunohistochemical features of newly formed vasculatures. Our hypothesis appears to be applicable to all epithelium-derived cancers. 相似文献