Abstract
The P2Y4 receptor is responsive to UTP in human and to ATP and UTP in rodents. With the aim of identifying its pharmacotherapeutic interest, we generated P2Y4-null mice by a classic gene targeting method. The proportion of genotypes was consistent with X-linked Mendelian transmission. Gene inactivation was checked by the complete disappearance of P2Y4 receptor mRNA from liver, stomach, and intestine. The P2Y4-null mice had a grossly normal behavior, growth, and reproduction. Chloride secretion by the jejunal epithelium was assessed in Ussing chambers by the measurement of the short circuit current in the presence of phlorizin. We show here that the UTP- and ATP-induced chloride secretory responses observed in wild-type mice are abolished in P2Y4-null mice. This is the first clearcut demonstration of a biological role of the P2Y4 receptor.
Footnotes
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This work was supported by the Fonds Forton, an Action de Recherche Concertée of the Communauté Française de Belgique, the Belgian Program on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Federal Service for Science, Technology and Culture, grants of the Fonds de la Recherche Scientifique Médicale, and the Fonds Emile DEFAY.
- Abbreviations:
- bp
- base pair(s)
- PCR
- polymerase chain reaction
- RT
- reverse transcription
- HPRT
- hypoxanthine phosphoribosyltransferase
- SSC
- short-circuit current
- 8-p-SPT
- 8-(para-sulfophenyl)theophylline
- ES
- embryonic stem
- CFTR
- cystic fibrosis transmembrane conductance regulator
- Received October 11, 2002.
- Accepted November 22, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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