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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes chloride and iodide effluxes across the basolateral membrane of porcine thyroid follicles reconstituted in culture. Basolateral chloride efflux is activated by thyrotropin (TSH). TSH (10 mU/ml) induces a twofold increase in the initial rate of chloride efflux. Forskolin (FSK, 5 microM) which increases intracellular cAMP also stimulates the initial rate of chloride efflux 3.5-fold, whereas an increase in the free cytosolic Ca2+ with the ionophore A23187 or thapsigargin, fails to mimic the TSH effect. The chloride channel blocker 5-nitro-2(3-phenylpropylamino)benzoic acid (NPPB) dose dependently inhibits chloride efflux rates with the maximal and half maximal effects observed for 100 microM and 30 microM, respectively. Basolateral chloride efflux rates are also inhibited in the presence of the organic anion transporter blocker probenecid (5 mM) or the Cl-/HCO3- exchanger blocker 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS, 250 microM), respectively, by 60% and 40%, whereas it is not affected by ClO4 (100 microM). The initial rate of iodide efflux is weakly activated (1.4-fold) by TSH (10 mU/ml). TSH effect could be reproduced by agents known to activate Ca(2+)-dependent processes as A23187, ionomycin (1 microM), phorbol 12-myristate 13-acetate (TPA, 0.1 microM) and epidermal growth factor (EGF, 0.1 microM) which increase the initial rate of iodide efflux from 1.2- to 1.8-fold, whereas FSK is without effect. The chloride channel blocker NPPB (500 microM) is required to significantly inhibit the initial rate of iodide efflux by 30%. The initial rate of iodide efflux is also reduced by 30% in the presence of SITS (250 microM) or probenecid (5 mM) whereas it is activated by ClO4 (100 microM). We conclude that basolateral chloride and iodide effluxes are both regulated by TSH, using two different transduction pathways. Chloride efflux regulation may involve a cAMP transduction signal, whereas the regulation of iodide efflux may involve a Ca2+ signal. Furthermore, as the sensitivities of chloride and iodide effluxes for the anion transporter blockers (especially NPPB) are different, it seems likely that chloride and iodide use two different transport pathways.
Mol Cell Endocrinol 1994 Dec
PMID:Thyrotropin regulation of basolateral Cl- and I- effluxes in thyroid follicles in culture. 789 8

The muscle chloride channel CIC-1 regulates the electric excitability of the skeletal muscle membrane. Mutations in the gene encoding this chloride channel (CLCN1) are responsible for both human purely myotonic disorders, autosomal recessive generalized myotonia (Becker's disease, GM) and autosomal dominant myotonia congenita (Thomsen's disease, MC). We now show that the protein-coding sequence of the CLCN1 gene is organized into 23 exons. The CIC-1 upstream region contains a canonical TATA box, several consensus binding sites for myogenic transcription factors and two other putative regulatory elements. SSCA analysis of a German GM family revealed that affected members are compound heterozygotes having two novel mutations. G979A affects a splice consensus site at the end of exon 8, and G1488T in exon 14 leads to a replacement of a positive charge in a highly conserved putative transmembrane domain (R496S). Functional expression of R496S cRNA in Xenopus oocytes did not yield detectable currents. It neither suppressed wild-type currents in a co-expression assay, confirming it as a recessive mutation.
Hum Mol Genet 1994 Jun
PMID:Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia. 795 Dec 42

Recessive myotonia congenita (Becker) is genetically linked to HUMCLC, the gene encoding the muscular chloride channel, localized on chromosome 7q35. Three point mutations have so far been reported in HUMCLC, one causing recessive Becker-type myotonia, the others causing the clinically similar Thomsen-type myotonia, which is inherited as a dominant trait. We report a homozygous patient having a 4 base pair deletion in HUMCLC that shifts the reading frame and causes early stop codons, thus destroying the gene's coding potential for several membrane-spanning domains. In addition, we report a patient homozygous for a novel point mutation located at the extracellular side of the first membrane-spanning domain that causes removal of a negative charge (aspartic acid-136-glycine). Both mutations lead to the recessive type of myotonia congenita. Since the patient having the deletion presents less severe clinical myotonia than the patient carrying the missense mutation, it seems that the absence or truncation of the channel protein may disturb muscle fibre function less than the substitution of a single amino acid.
Hum Mol Genet 1994 Jul
PMID:Proof of a non-functional muscle chloride channel in recessive myotonia congenita (Becker) by detection of a 4 base pair deletion. 798 81

Progesterone elicits a rapid, transient calcium influx in sperm that is a prerequisite for the progesterone-induced acrosome reaction. The possibility that the GABAA receptor/chloride channel was the receptor that mediated the progesterone-induced calcium influx in human sperm was examined. A-ring reduced 3 alpha-hydroxy pregnane steroids (e.g. alfaxalone, allopregnanolone, pregnanolone), which are active on the GABAA receptor/chloride channel, were found to be much weaker than progesterone at stimulating Ca2+ influx in sperm. The effects of a variety of progesterone metabolites and analogs and other steroids were compared for their ability to (i) stimulate GABA-induced 36Cl- uptake in synaptoneurosomes, (ii) stimulate GABA-induced Cl- currents in HEK-293 cells transfected with alpha 1, beta 2, and gamma 2 subunits of the GABAA receptor/chloride complex, and (iii) elicit a rapid Ca2+ influx in sperm. No correlation was observed between the ability of a given steroid to stimulate Ca2+ influx and efficacy in eliciting either 36Cl- uptake or chloride currents. Importantly, the action of progesterone to stimulate Ca2+ influx was not modified by GABA, diazepam, picrotoxin and pentobarbitol (known regulators of the GABAA receptor/chloride channel). It is concluded from these studies that the cell surface progesterone binding site on human sperm that mediates progesterone-induced changes in [Ca2+]i is unlike the steroid binding site on the GABAA receptor/chloride channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Sep
PMID:The cell surface progesterone receptor which stimulates calcium influx in human sperm is unlike the A ring reduced steroid site on the GABAA receptor/chloride channel. 798 50

Messenger RNA (mRNA) for several subunits of the GABAA receptor was measured in the cortex of mice chemically kindled with FG 7142. At 10 days after the final FG 7142 injection, beta 2 and gamma 2S subunit mRNA were significantly increased. At 31 days, alpha 1, alpha 3, beta 2, and gamma 2L mRNA were elevated. In contrast, levels of mRNA for four subunits of the glutamate receptor in the cortex of FG 7142-kindled mice killed at 31 days were not significantly increased. Previous investigations have shown a reduction in GABA-gated chloride channel function and density in mice kindled with FG 7142, and the increases in subunit mRNA found in the present studies may be a response to these decreases. These results indicate that chemical kindling produces long-lasting changes in expression of genes coding for specific neurotransmitter receptor subunits.
Brain Res Mol Brain Res 1994 Mar
PMID:GABAA and glutamate receptor subunit mRNAs in cortex of mice chemically kindled with FG 7142. 801 88

A polymerase chain reaction (PCR)-based homology probing strategy was employed to screen Drosophila melanogaster genomic DNA for sequences encoding a conserved amino acid 'signature motif' known to be present in vertebrate GABA receptor and glycine receptor subunit genes. This approach yielded three discrete amplified sequence elements (designated LCCH1, LCCH2, and LCCH3) that contained open reading frames and > 40% amino acid sequence identity to the corresponding regions of vertebrate ligand-gated chloride channel genes. Genomic DNA clones corresponding to each element were isolated and sequenced, and predicted amino acid sequences corresponding to the second (M2) and third (M3) transmembrane domains of vertebrate genes were analyzed for identity or similarity to known sequences. LCCH1 was identical to the Rdl gene, a known GABA receptor subunit gene from D. melanogaster, whereas LCCH2 and LCCH3 were novel D. melanogaster sequences that exhibited structural similarity to other members of the ligand-gated chloride channel gene family. LCCH2 was equally divergent in M2 and M3 (46-49% amino acid identity) from all other known members of this family and may therefore represent a new subunit or receptor class within this family. LCCH2 was localized by in situ hybridization to cytogenetic region 75A on the left arm of chromosome 3. LCCH3 was closely related to mammalian (79% amino acid identity) and snail (96% amino acid identity) GABA receptor beta subunits and may therefore be the homologue in D. melanogaster of this subunit class. LCCH3 was localized by in situ hybridization to cytogenetic region 13F on the X chromosome.(ABSTRACT TRUNCATED AT 250 WORDS)
Insect Biochem Mol Biol 1994 Apr
PMID:PCR-based homology probing reveals a family of GABA receptor-like genes in Drosophila melanogaster. 802 58

Many types of chloride current have been reported in the hearts of various species; however, the nature of chloride conductance in the human heart is still unclear. We investigated cyclic AMP-dependent chloride current and swelling-induced chloride current in isolated human atrial cells using the whole-cell voltage-clamp method. External application of 1 microM isoprenaline increased calcium current by 391.9 +/- 48.6% (mean +/- S.D., n = 8); however, there was no activation of cyclic AMP-dependent chloride current at steady-state membrane potentials between -80 and +50 mV. Neither external application of 10 microM forskolin nor internal application of 50 microM cyclic AMP activated a cyclic AMP-dependent chloride current. On the other hand, when the same cell was superfused with a 50% hypotonic solution, it exhibited osmotic swelling and an outward rectifying current (6.59 +/- 0.96 pA/pF at +30 mV, n = 10). This swelling-induced current reversed at -26.5 +/- 3.1 mV (n = 10), close to the calculated equilibrium potential for chloride, and it was sensitive to the stilbene-derivative chloride channel blocker. In conclusion, no activation of cyclic AMP-dependent chloride current was observed in human atrial cells. On the other hand, a swelling-induced chloride current was consistently demonstrated and its kinetic properties were similar to those reported in other cardiac myocytes.
J Mol Cell Cardiol 1995 Oct
PMID:Chloride conductance in human atrial cells. 857 55

A number of recent observations suggest a link between airway Cl-transport and asthma. We have previously described the properties of a voltage- and Ca2+ -dependent chloride channel present in airway epithelium. We now show that agents able to prevent indirectly induced bronchoconstriction (sodium cromoglycate, nedocromil sodium, and furosemide) reduce either the single-channel conductance or the open probability of this channel. The effects of these agents and the Ca2+ dependence of the channel are localized to the same surface, and we show that the channel possesses a specific divalent cation binding site, which responds to concentrations of Ca2+ found on the airway mucosal surface. No alteration of the single-channel properties of this channel were seen in cystic fibrosis epithelium. These data suggest a mechanism by which structurally diverse agents may influence asthma.
Am J Respir Cell Mol Biol 1996 Apr
PMID:Asthma prophylaxis agents alter the function of an airway epithelial chloride channel. 860 Sep 43

CIC-2 is a voltage- and volume-regulated chloride channel expressed in many tissues. We have shown that CIC-2 in rat lung airways is significantly down-regulated after birth [Murray,C.B. et al. (1995) Am. J. Respir. Cell Mol. Biol., 12, 597-604]. During PCR amplification from rat lung cDNA, a second transcript was identified which is 60 bp shorter than the full length sequence. The peptide translated from this 60 bp sequence contains many positively charged amino acid residues. Rat genomic DNA sequencing showed that the 60 bp sequence is an intact exon. A 71% pyrimidine content and an AAG 3'-end splice site in the intron immediately upstream from the 60 bp sequence were identified which may account for the alternative splicing of the following exon. Human genomic sequence analyses demonstrated similar intron-exon arrangement. A high CT content and an AAG 3' acceptor site were conserved in the intron corresponding to the rat upstream intron. The presence of the full length short form transcript was confirmed in rat kidney by RT-PCR, and the ratio of the long and the short form transcripts varied significantly according to the tissues examined, with the lowest long/short form ratio found in the lung among the tissues studied. Our data demonstrated that the alternatively spliced short form (CIC-2S) is transcribed in many rat tissues, the ratio of the long/short form transcripts is lower in the lung compared with the brain, and the genomic organization in this area is conserved in rat and human.
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PMID:A short CIC-2 mRNA transcript is produced by exon skipping. 881 Nov 2

P-glycoprotein (pgp) is a membrane transport protein that causes multidrug resistance (MDR) by actively extruding a wide variety of cytotoxic agents out of cells. It may also function as a peptide transporter, a volume-regulated chloride channel, and an ATP channel. Previously, it has been shown that hamster pgp 1 Pgp is expressed in more than one topological form and that the generation of these structures is modulated by charged amino acids flanking the predicted transmembrane (TM) segments 3 and 4 and by soluble cytoplasmic factors. Different topological structures of Pgp may be related to its different functions. In this study, we examined the effects of translation temperature on the membrane insertion process and the topologies of Pgp. Using the rabbit reticulocyte lysate expression system, we showed that translation at different temperatures affects the membrane insertion and orientation of the putative TM3 and TM4 of hamster pgp 1 Pgp in a co-translational manner. This observation suggests that the membrane insertion process of TM3 and TM4 of Pgp molecules may involve a protein conducting channel and/or the interaction between TM3 and TM4, which act in a temperature sensitive manner. We speculate that manipulating temperature may provide a way to understand the structure-function relationship of Pgp and help overcome Pgp-related multidrug resistance of cancer cells.
Mol Cell Biochem 1996 Jun 07
PMID:Co-translational effects of temperature on membrane insertion and orientation of P-glycoprotein sequences. 881 6


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