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Biomedical subjects

A Laich

Publications and source records attributed to A Laich.

6 recordsLinked to original sources
PubMed2000

The gastric H,K-ATPase blocker lansoprazole is an inhibitor of chloride channels.

1. It was postulated that swelling dependent chloride channels are involved in the proton secretion of parietal cells. Since omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 are structurally related to phenol derivatives known to block swelling dependent chloride channels, we set out to test, whether these substances--which are known to block the H,K-ATPase--could also lead to an inhibition of swelling-dependent chloride channels. Swelling-dependent chloride channels--characterized in many different cell types--show highly conserved biophysical and pharmacological features, therefore we investigated the effect of omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 on swelling-dependent chloride channels elicited in fibroblasts, after the reduction of the extracellular osmolarity. 2. Omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 are able to block swelling-dependent chloride channels (IClswell). 3. Lansoprazole and its protonated metabolite AG2000 act on at least two different sites of the IClswell protein: on an extracellular site which seems to be in a functional proximity to the nucleotide binding site, and on an intracellular site which allows the formation of disulfide-bridges. 4. The inhibition of the proton pump and the simultaneous blocking of chloride channels by omeprazole, lansoprazole and its acid activated sulphenamide form AG2000, as described here could be an effective mode to restrict proton secretion in parietal cells.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Structure and expression of the human small cytokine B subfamily member 11 (SCYB11/formerly SCYB9B, alias I-TAC) gene cloned from IFN-gamma-treated human monocytes (THP-1).

Among CXC chemokines, monokine induced by interferon-gamma (IFN-gamma) (MIG) and IGN-gamma-inducible protein, 10 kDa (INP10), constitute a distinct group because of their sequence and function. We studied genomic structure and expression of a third, recently identified member of this group named small inducible cytokine B subfamily member 11 (SCYB11, formerly SCYB9B) or IFN-inducible T cell alpha chemoattractant (I-TAC). The cDNA (1445 bp) for this 94 amino acid protein (Mr 10,364) was cloned from IFN-gamma-treated human myelomonocytic cells (THP-1). The reading frame of SCYB11 is distributed to 4 exons spanning 1197 bp of the genomic sequence. In vitro transcription/translation yielded a single protein of about 10 kDa, indicating that the deduced reading frame is translated by eukaryotic ribosomes. The recombinant 73 amino acid mature protein overexpressed in Escherichia coli was chemotactic for interleukin-2 (IL-2)-selected T memory cells. Studying various cytokines and lipopolysaccharide in THP-1 cells identified IFN-gamma as the major stimulus for SCYB11 mRNA expression, followed by IFN-alpha and IFN-beta, which were about 25 times less effective. Of a panel of different human cells tested, SCYB11 mRNA was also induced in umbilical vein endothelial cells, dermal fibroblasts, and tumor cell lines from various organs, whereas it was not found in T lymphocytes activated via anti-CD3 antibodies or via IL-2.

Amino Acid Sequence↗
PubMed1996

ICln: a chloride channel paramount for cell volume regulation.

Cell volume regulation is a ubiquitous cell regulatory mechanism based on meticulously controlled ion transport mechanisms. Keeping the absolute volume constant seems to be of the highest priority for most cells and is achieved at the expense of altered intracellular ion concentrations. We have been able to demonstrate that ICln, a chloride channel cloned from epithelial cells, is paramount for the ability of swollen cells to regulate their volume back to that under resting conditions. A unique feature of ICln is the distinct sensitivity of these channels for nucleotides and nucleoside analogues added to the extracellular fluid. In addition, cromolyn sodium and nedocromil sodium, drugs used by patients with asthma, are able to impede the function of these channels.

Animals↗
PubMed1995

Antiviral drugs from the nucleoside analog family block volume-activated chloride channels.

BACKGROUND: The antiviral drugs AZT and acyclovir are generally used in the treatment of infections with human immunodeficiency virus (HIV) and herpes simplex virus (HSV). These substances are known to impede virus replication by premature nucleic acid chain termination. It is not yet clear, however, if this is the sole mechanism responsible for the antiviral and/or the numerous side effects observed in patients treated with these agents. We investigated the swelling-induced chloride current in fibroblasts, which we demonstrated is closely related or identical to a cloned epithelial chloride channel, ICln: This chloride channel can be blocked by nucleotides. MATERIALS AND METHODS: Electrophysiological, fluorescence optical, and volume measurements were made to determine the effect of nucleoside analogs on the swelling-dependent chloride current (ICl) in NIH 3T3 fibroblasts and in human T cell lymphoma (H9) cells and the cAMP-dependent chloride current in CaCo cells. RESULTS: AZT and acyclovir block the swelling-dependent chloride current and the chloride flux in fibroblasts, and the regulatory volume decrease (RVD) and ICl in H9 cells. This immediate effect can be substantially reduced by the simultaneous incubation of the cells with thymidine-5'-diphosphate (TDP) or uridine, both of which are by themselves unable to affect ICl. CONCLUSIONS: We show here a novel molecular mechanism by which antiviral drugs of the nucleoside analog family could lead to impairments of the kidney, bone marrow, gastrointestinal, and neuronal functions, and how these side effects could possibly be restricted by the presence of TDP or uridine.

3T3 Cells↗