Loss of nucleotide regulation of epithelial chloride transport in the jejunum of P2Y4-null mice.
The P2Y(4) receptor is responsive to UTP in human and to ATP and UTP in rodents. With the aim of identifying its pharmacotherapeutic interest, we generated P2Y(4)-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 P2Y(4) receptor mRNA from liver, stomach, and intestine. The P2Y(4)-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 P2Y(4)-null mice. This is the first clearcut demonstration of a biological role of the P2Y(4) receptor.
Robaye
Bernard
B
Institute of Interdisciplinary Research, Institute of Biology and Molecular Medicine, Université Libre de Bruxelles, Gosselies, Belgium. brobaye@ulb.ac.be
Ghanem
Esam
E
Wilkin
Françoise
F
Fokan
Dominique
D
Van Driessche
Willy
W
Schurmans
Stéphane
S
Boeynaems
Jean-Marie
JM
Beauwens
Renaud
R
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D007583:Jejunum / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000494:pharmacology
D002712:Chlorides; D018048:Receptors, Purinergic P2; C104749:purinoceptor P2Y4; D000255:Adenosine Triphosphate; D014544:Uridine Triphosphate