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61.
Boll M Foltz M Rubio-Aliaga I Kottra G Daniel H 《The Journal of biological chemistry》2002,277(25):22966-22973
We cloned two cDNAs encoding proton/amino acid cotransporters, designated as mPAT1 and mPAT2, from murine tissues. They were identified by sequence similarity to the amino acid/auxin permease family member of lower eukaryotes. We functionally characterized both transporters by flux studies and electrophysiology after expression in Xenopus laevis oocytes. Both mPAT1 and mPAT2 induced a pH-dependent electrogenic transport activity for small amino acids (glycine, alanine, and proline) that is altered by membrane potential. Direct evidence for amino acid/H(+)-symport was shown by intracellular acidification, and a flux coupling stoichiometry for proline/H(+)-symport of 1:1 was determined for both transporters. Besides small apolar L-amino acids, the transporters also recognize their D-enantiomers and selected amino acid derivatives such as gamma-aminobutyric acid. The mPAT1 transporter, the murine orthologue of the recently cloned rat LYAAT-1 transporter, can be considered as a low affinity system when compared with mPAT2. The mRNA of mPAT1 is highly expressed in small intestine, colon, kidney, and brain; the mPAT2-mRNA is mainly found in heart and lung. Phenotypically, the PAT1 transporter possesses the same functional characteristics as the previously described proton-dependent amino acid transport process in apical membranes of intestinal and renal epithelial cells. 相似文献
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Vermes C Jacobs JJ Zhang J Firneisz G Roebuck KA Glant TT 《The Journal of biological chemistry》2002,277(19):16879-16887
Human osteoblasts produce interleukin-6 (IL-6) and respond to IL-6 in the presence of soluble IL-6 receptor (sIL-6R), but the cell surface expression of IL-6R and the mechanism of sIL-6R production are largely unknown. Three different human osteoblast-like cell lines (MG-63, HOS, and SaOS-2) and bone marrow-derived primary human osteoblasts expressed both IL-6R and gp130 as determined by flow cytometry and immunoprecipitation. However, the membrane-bound IL-6R was nonfunctional, as significant tyrosine phosphorylation of gp130 did not occur in the presence of IL-6. Phorbol myristate acetate induced a dramatic increase of both IL-6R shedding (i.e. the production of sIL-6R) and IL-6 release in osteoblast cultures, but the cell surface expression of gp130 remained unchanged. IL-6 complexed with sIL-6R, either exogenously introduced or derived from the nonfunctional cell surface form by shedding, induced rapid tyrosine phosphorylation of gp130. This effect was inhibited by neutralizing antibodies to either sIL-6R or gp130, indicating that the gp130 activation was induced by IL-6/sIL-6R/gp130 interaction. Protein kinase C inhibitors blocked phorbol myristate acetate-induced and spontaneous shedding of IL-6R resulting in the absence of sIL-6R in the culture medium, which in turn also prevented the activation of gp130. In conclusion, human osteoblasts express cell surface IL-6R, which is unable to transmit IL-6-induced signals until it is shed into its soluble form. This unique mechanism provides the flexibility for osteoblasts to control their own responsiveness to IL-6 via the activation of an IL-6R sheddase, resulting in an immediate production of functionally active osteoblast-derived sIL-6R. 相似文献
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Background
Short tandem repeat polymorphisms (STRPs) are powerful tools for gene mapping and other applications. A STRP genome scan of 10 cM is usually adequate for mapping single gene disorders. However mapping studies involving genetically complex disorders and especially association (linkage disequilibrium) often require higher STRP density. 相似文献66.
Dendritic spines receive excitatory synapses and serve as calcium compartments, which appear to be necessary for input-specific synaptic plasticity. Dendrites of GABAergic interneurons have few or no spines and thus do not possess a clear morphological basis for synapse-specific compartmentalization. We demonstrate using two-photon calcium imaging that activation of single synapses on aspiny dendrites of neocortical fast spiking (FS) interneurons creates highly localized calcium microdomains, often restricted to less than 1 microm of dendritic space. We confirm using ultrastructural reconstruction of imaged dendrites the absence of any morphological basis for this compartmentalization and show that it is dependent on the fast kinetics of calcium-permeable (CP) AMPA receptors and fast local extrusion via the Na+/Ca2+ exchanger. Because aspiny dendrites throughout the CNS express CP-AMPA receptors, we propose that CP-AMPA receptors mediate a spine-free mechanism of input-specific calcium compartmentalization. 相似文献
67.
Inhibition of TASK-1 potassium channel by phospholipase C 总被引:11,自引:0,他引:11
Czirjak Gabor; Petheo Gabor L.; Spat Andras; Enyedi Peter 《American journal of physiology. Cell physiology》2001,281(2):C700
Thetwo-pore-domain K+ channel, TASK-1, was recently shown tobe a target of receptor-mediated regulation in neurons and in adrenalglomerulosa cells. Here, we demonstrate that TASK-1 expressed inXenopus laevis oocytes is inhibited by differentCa2+-mobilizing agonists. Lysophosphatidic acid, via itsendogenous receptor, and ANG II and carbachol, via their heterologouslyexpressed ANG II type 1a and M1 muscarinic receptors,respectively, inhibit TASK-1. This effect can be mimicked by guanosine5'-O-(3-thiotriphosphate), indicating the involvementof GTP-binding protein(s). The phospholipase C inhibitor U-73122reduced the receptor-mediated inhibition of TASK-1. Downstream signalsof phospholipase C action (inositol 1,4,5-trisphosphate, cytoplasmicCa2+ concentration, and diacylglycerol) do not mediate theinhibition. Unlike the Gq-coupled receptors, stimulation ofthe Gi-activating M2 muscarinic receptorcoexpressed with TASK-1 results in an only minimal decrease of theTASK-1 current. However, additional coexpression of phospholipaseC-2 (which is responsive also to Gi-subunits) renders M2 receptor activation effective.This indicates the significance of phospholipase C activity in thereceptor-mediated inhibition of TASK-1. 相似文献
68.
Nantermet PG Barrow JC Selnick HG Homnick CF Freidinger RM Chang RS O'Malley SS Reiss DR Broten TP Ransom RW Pettibone DJ Olah T Forray C 《Bioorganic & medicinal chemistry letters》2000,10(15):1625-1628
A series of alpha1a receptor antagonists derived from a 4-aryl-3,4-dihydropyridine-2-one heterocycle is disclosed. Potency in the low nanomolar to picomolar range along with high selectivity was obtained. In vivo efficacy in a prostate contraction model in rats was observed with a few derivatives. 相似文献
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