Indomethacin and piroxicam inhibit Na+-adenosine transport in rat renal brush-border membranes.
The effects of the cyclooxygenase inhibitors, indomethacin and piroxicam, were evaluated on Na+-dependent [3H]adenosine transport in rat renal brush-border membranes of the outer renal cortex of the rat. Adenosine co-transport (1-10 microM) was estimated in the presence of 0.001-10 microM indomethacin and piroxicam. Both drugs inhibited the Na+-dependent transport in a dose-dependent manner with IC50 of 3.5 microM and 0.1 microM, respectively. The Na+-independent transport was not modified. Preincubations carried out on the vesicles with 10-50 microM arachidonic acid increased transport in a dose-dependent manner up to 1.7 times. Whereas 50 pM to 5 microM prostaglandin E2 in the presence of indomethacin did not change carrier activity, 5 microM prostaglandin E2 increased the Na+-dependent transport 1.5 times. Other prostanoid synthesis pathways were investigated with 10 microM nordihydroguaiaretic acid (lipoxygenase inhibitor), and 17-octadecynoic acid and clotrimazole (leukotriene and cytochrome P450 inhibitors). Our results demonstrated that the Na+-dependent adenosine transport in brush-border membranes was inhibited by indomethacin and piroxicam, suggesting that cyclooxygenase activity might modulate this co-transport.
González-Castillo
C
C
Department of Pharmacology, Facultad de Medicina de la Universidad Autónoma de San Luis Potosí, SLP, Mexico.
Franco
M
M
Quintana
A
A
Escalante
B
B
Martínez
F
F
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D010894:Piroxicam / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D010894:Piroxicam; D016718:Arachidonic Acid; D012964:Sodium; D000241:Adenosine; D015232:Dinoprostone; D007213:Indomethacin