Leptin decreases renal medullary Na(+), K(+)-ATPase activity through phosphatidylinositol 3-kinase dependent mechanism

• Published in: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2004-06, Vol.55 (2), p.391-407
• Main Authors: Bełtowski, J, Marciniak, A, Wójcicka, G
• Format: Article
• Language: English
• Subjects: Animals; Cyclic GMP - metabolism; Diuresis - drug effects; Enzyme Inhibitors - pharmacology; Infusions, Intra-Arterial; Kidney Function Tests; Kidney Medulla - drug effects; Kidney Medulla - enzymology; Leptin - administration & dosage; Leptin - pharmacology; Male; Natriuretic Peptides - metabolism; Nitric Oxide - metabolism; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase - metabolism
• ISSN: 0867-5910

We examined the effect of leptin on renal function and renal Na(+),K(+)-ATPase and ouabain-sensitive H(+),K(+)-ATPase activities in the rat. Leptin was infused under general anaesthesia into the abdominal aorta proximally to the renal arteries. Leptin infused at doses of 1 and 10 microg/kg/min increased urine output by 40% and 140%, respectively. Urinary Na(+) excretion increased in rats receiving leptin at doses of 0.1, 1, and 10 microg/kg/min by 57.6%, 124.2% and 163.6%, respectively. Leptin had no effect on creatinine clearance, potassium excretion and phosphate excretion. Na(+),K(+)-ATPase activity in the renal medulla of rats treated with 1 and 10 microg/kg/min leptin was lower than in control animals by 25.5% and 33.2%, respectively. In contrast, cortical Na(+),K(+)-ATPase as well as either cortical or medullary ouabain-sensitive H(+),K(+)-ATPase activities did not differ between leptin-treated and control animals. The effect of leptin on Na(+),K(+)-ATPase activity was abolished by actin depolymerizing agents, cytochalazin D and latrunculin B, and by phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002. These results indicate that: 1). natriuretic effect of leptin is mediated, at least in part, by decrease in renal medullary Na(+),K(+)-ATPase activity, 2). inhibition of medullary Na(+),K(+)-ATPase by leptin is mediated by PI3K and requires integrity of actin cytoskeleton.