The Cl- secretory pathway that is defective in cystic fibrosis (CF) can be bypassed by an alternative pathway for Cl- transport that is activated by extracellular nucleotides. Accordingly, the P2 receptor that mediates this effect is a therapeutic target for improving Cl- secretion in CF patients. In this paper, we report the sequence and functional expression of a cDNA cloned from human airway epithelial (CF/T43) cells that encodes a protein with properties of a P2U nucleotide receptor. With a retrovirus system, the human airway clone was stably expressed in 1321N1 astrocytoma cells, a human cell line unresponsive to extracellular nucleotides. Studies of inositol phosphate accumulation and intracellular Ca2+ mobilization induced by extracellular nucleotides in 1321N1 cells expressing the receptor identified this clone as the target receptor in human airway epithelia. In addition, we independently isolated an identical cDNA from human colonic epithelial (HT-29) cells, indicating that this is the same P2U receptor that has been functionally identified in other human tissues. Expression of the human P2U receptor (HP2U) in 1321N1 cells revealed evidence for autocrine ATP release and stimulation of transduced receptors. Thus, HP2U expression in the 1321N1 cell line will be useful for studying autocrine regulatory mechanisms and in screening of potential therapeutic drugs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC43559 | PMC |
| http://dx.doi.org/10.1073/pnas.91.8.3275 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Diverse plant RNAs coat leaves and are distinct from apoplastic RNAs.
Proc Natl Acad Sci U S A
January 2025
Department of Biology, Indiana University, Bloomington, IN 47405.
Transgenic expression of a double-stranded RNA in plants can induce silencing of homologous mRNAs in fungal pathogens. Although such host-induced gene silencing is well documented, the molecular mechanisms by which RNAs can move from the cytoplasm of plant cells across the plasma membrane of both the host cell and fungal cell are poorly understood. Indirect evidence suggests that this RNA transfer may occur at a very early stage of the infection process, prior to breach of the host cell wall, suggesting that silencing RNAs might be secreted onto leaf surfaces.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Stanford University, School of Medicine, Stanford, CA, USA.
Background: Several lines of evidence now suggest that ABCA1 plays a role in Alzheimer's disease (AD). Rare variants on ABCA1 increased AD risk in a large genetic study, and mouse models suggest that increasing ABCA1 activity can reverse signs of AD pathology. While there is growing consensus that ABCA1 and ApoE directly interact, it is unclear how APOE genotype affects this interaction in the context of neurodegeneration.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
The University of Tokyo, Tokyo, Japan.
Background: Recent genome-wide association analysis has identified Bridging Integrator 1 (BIN1) as one of the genetic risk factors for late-onset AD. In AD patients, single nucleotide polymorphisms in BIN1 correlate well with tau pathology, suggesting the involvement of BIN1 in the formation and propagation of tau accumulation pathology, but the molecular mechanism and point of action remain unclear.
Method: To comprehensively clarify the effects of BIN1 on two pathological events, tau aggregation and propagation, we analyzed BIN1 knockout mice.
Eribulin Induction of Immunogenic Cell Death (ICD): Comparison With Other Cytotoxic Agents and Temporal Relationship of ICD Biomarkers.
Anticancer Res
January 2025
Eisai Inc., Cambridge, MA, U.S.A.
Background/aim: Preclinical studies were undertaken to investigate whether eribulin's known cytotoxic antimitotic effects are characterized by immunogenic cell death (ICD) as assessed by three established ICD biomarkers: extracellular released ATP, released HMGB1 and cell surface calreticulin.
Materials And Methods: Using BT-549, Hs578T and MCF-7 breast cancer cell lines, antiproliferative IC's of eribulin, five other microtubule targeting agents (MTAs; ER-076349, vinblastine, vinorelbine, paclitaxel, docetaxel) and three DNA damaging agents (DDAs; doxorubicin, cisplatin, oxaliplatin) were determined.
Results: Treatment of cells with 10×IC concentrations of all drugs in serum-free media resulted in time-dependent induction of cytotoxicity over DMSO controls.
ClC-5 knockout mitigates angiotensin II-induced hypertension and endothelial dysfunction.
Life Sci
December 2024
Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address:
Aims: Impairment of nitric oxide (NO) production is a major cause of endothelial dysfunction and hypertension. ClC-5 Cl channel is abundantly expressed in the vascular endothelium. However, it remains unclear how it regulates endothelial function.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!