RT Journal Article
SR Electronic
T1 Loss of Nucleotide Regulation of Epithelial Chloride Transport in the Jejunum of P2Y<sub>4</sub>-Null Mice
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 777
OP 783
DO 10.1124/mol.63.4.777
VO 63
IS 4
A1 Bernard Robaye
A1 Esam Ghanem
A1 Françoise Wilkin
A1 Dominique Fokan
A1 Willy Van Driessche
A1 Stéphane Schurmans
A1 Jean-Marie Boeynaems
A1 Renaud Beauwens
YR 2003
UL http://molpharm.aspetjournals.org/content/63/4/777.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics