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Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy.
Open accessAbstract
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.
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Cited by
Purinoceptors: Are there families of P2X and P2Y purinoceptors?
Abbracchio, M. P., & Burnstock, G. (1994) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(94)00048-4 · Cited by 1,083
Extracellular ATP or ADP Induce Chemotaxis of Cultured Microglia through Gi/o-Coupled P2Y Receptors
Honda, S., Sasaki, Y., Ohsawa, K., Imai, Y., Nakamura, Y., Inoue, K., & Kohsaka, S. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-06-01975.2001 · Cited by 561
CFTR-independent ATP release from epithelial cells triggered by mechanical stimuli
Grygorczyk, R., & Hanrahan, J. W. (1997) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1997.272.3.c1058 · Cited by 258
Metadata
- Authors
- Parr, C. E., Sullivan, D. M., Paradiso, A. M., Lazarowski, E. R., Burch, L. H., Olsen, J. C., Erb, L., Weisman, G. A., Boucher, R. C., & Turner, J. T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1994-04-12
- Volume
- 91
- Issue
- 8
- Pages
- 3275-3279
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2123382745
- Cited by
- 410
- References
- 0
- FWCI
- 19.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Parr, C. E., Sullivan, D. M., Paradiso, A. M., Lazarowski, E. R., Burch, L. H., Olsen, J. C., Erb, L., Weisman, G. A., Boucher, R. C., & Turner, J. T. (1994). Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.91.8.3275
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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