Effect of loss of P2Y2 receptor gene expression on nucleotide regulation of murine epithelial Cl- transport

Victoria L. Cressman, Eduardo Lazarowski, L. Homolya, Richard C. Boucher, Beverly H. Koller, Barbara R. Grubb

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Extracellular nucleotides are believed to be important regulators of ion transport in epithelial tissues as a result of their ability to activate cell surface receptors. Although numerous receptors that bind nucleotides have been identified, the complexity of this receptor family, combined with the lack of pharmacological agents specific for these receptors, has made the assignment of particular receptors and ligands to physiological responses difficult. Because ATP and UTP appear equipotent and equieffective in regulating ion transport in many epithelia, we tested the hypothesis that the P2Y2 receptor (P2Y2-R) subtype mediates these responses in mouse epithelia, with gene targeting techniques. Mice with the P2Y2-R locus targeted and inactivated (P2Y2-R(-/-)) were generated, airways (trachea), gallbladder, and intestines (jejunum) excised, and Cl- secretory responses to luminal nucleotide additions measured in Ussing chambers. Comparison of P2Y2R(+/+) with P2Y2-R(-/-) mice revealed that P2Y2-R mediated most (>85-95%) nucleotide-stimulated Cl- secretion in trachea, about 50% of nucleotide responses in the gallbladder, and none of the responses in the jejunum. Dose- effect relationships for nucleotides in tissues from P2Y2-R(-/-) mice suggest that the P2Y6-R regulates ion transport in gallbladder and to a lesser extent trachea, whereas P2Y4 and/or unidentified receptor(s) regulate ion transport in jejunum. We conclude that the P2Y2 receptor is the dominant P2Y purinoceptor that regulates airway epithelial ion transport, whereas other P2Y receptor subtypes are relatively more important in other nonrespiratory epithelia.

Original languageEnglish
Pages (from-to)26461-26468
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number37
DOIs
Publication statusPublished - Sep 10 1999

Fingerprint

Purinergic P2Y2 Receptors
Gene expression
Ion Transport
Nucleotides
Gene Expression
Ions
Jejunum
Epithelium
Trachea
Gallbladder
Purinergic P2Y Receptors
Tissue
Uridine Triphosphate
Gene Targeting
Cell Surface Receptors
Intestines
Genes
Adenosine Triphosphate
Pharmacology
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Effect of loss of P2Y2 receptor gene expression on nucleotide regulation of murine epithelial Cl- transport. / Cressman, Victoria L.; Lazarowski, Eduardo; Homolya, L.; Boucher, Richard C.; Koller, Beverly H.; Grubb, Barbara R.

In: Journal of Biological Chemistry, Vol. 274, No. 37, 10.09.1999, p. 26461-26468.

Research output: Contribution to journalArticle

Cressman, Victoria L. ; Lazarowski, Eduardo ; Homolya, L. ; Boucher, Richard C. ; Koller, Beverly H. ; Grubb, Barbara R. / Effect of loss of P2Y2 receptor gene expression on nucleotide regulation of murine epithelial Cl- transport. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 37. pp. 26461-26468.
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