Characterization and localization of leptin receptors in the rat kidney.
Characterization and localization of leptin binding sites were investigated in rat kidneys using [125I]leptin as a ligand. [125I]Leptin specific binding was found in high amounts in rat renomedullary membranes. This binding was specific, saturable, time-dependent (K(obs) = 0.055 +/- 0.008 min(-1)) and the dissociation of receptor-bound ligand was slowly reversible (K(-1) = 0.048 +/- 0.013 min(-1)). From saturation experiments, a single class of high-affinity binding sites for leptin was identified with an apparent K(d) of 0.57 +/- 0.14 nM and a B(max) of 45 +/- 10 fmol/mg protein. [125I]Leptin binding was inhibited in a dose-dependent manner by cold leptin and was highly selective since not displaceable by a number of other hormones or peptides. Autoradiographic experiments performed on adult rat kidney sections showed the intense presence of [125I]leptin receptors only in specific areas of the renal inner medulla and also consistent labeling associated with vascular structures in the corticomedullary region. The study of the postnatal developmental expression of leptin receptors in the kidney showed very low expression during the early postnatal period (8-21 days). Full expression of leptin sites was achieved at about 30 days and remained stable throughout adulthood (60 days and upwards). Moreover, in vivo administration of leptin (0.5 mg/kg i.p.) induced a significant and rapid diuretic effect in normally hydrated conscious rats. Thus, these data constitute the first characterization and mapping of [125I]leptin specific binding sites in the rat kidney and raise the possibility of a renal control by leptin.
Serradeil-Le Gal
C
C
Sanofi Recherche, Exploratory Research Department, Toulouse, France.
Raufaste
D
D
Brossard
G
G
Pouzet
B
B
Marty
E
E
Maffrand
J P
JP
Le Fur
G
G
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects*; D007457:Iodine Radioisotopes; D007668:Kidney / Q000254:growth & development / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism; D007700:Kinetics; D020738:Leptin; D008297:Male; D009765:Obesity; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000378:metabolism; D054411:Receptors, Leptin
D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D020738:Leptin; D011506:Proteins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D054411:Receptors, Leptin