PKC stimulated by glucagon decreases UT-A1 urea transporter expression in rat IMCD.
It is well-known that glucagon increases fractional excretion of urea in rats after a protein intravenous infusion. This effect was investigated by using: (a) in vitro microperfusion technique to measure [(14)C]-urea permeability (Pu x 10(-5)cm/s) in inner medullary collecting ducts (IMCD) from normal rats in the presence of 10(-7)M of glucagon and in the absence of vasopressin and (b) immunoblot techniques to determine urea transporter expression in tubule suspension incubated with the same glucagon concentration. Seven groups of IMCDs (n = 47) were studied. Our results revealed that: (a) glucagon decreased urea reabsorption dose-dependently; (b) the glucagon antagonist des-His(1)-[Glu(9)], blocked the glucagon action but not vasopressin action; (c) the phorbol myristate acetate, decreased urea reabsorption but (d) staurosporin, restored its effect; e) staurosporin decreased glucagon action, and finally, (f) glucagon decreased UT-A1 expression. We can conclude that glucagon reduces UT-A1 expression via a glucagon receptor by stimulating PKC.
Yano
Yuristella
Y
Laboratório de Pesquisa Básica-LIM 12, Hospital das Clínicas da Faculdade de Medicina-Nefrologia, Universidade de São Paulo, Av Dr Arnaldo, 455, São Paulo, SP, 01246-903, Brasil.
Rodrígues
Adilson C
AC
de Bragança
Ana C
AC
Andrade
Lucia C
LC
Magaldi
Antonio J
AJ
D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D015536:Down-Regulation / Q000187:drug effects; D004586:Electrophoresis; D005934:Glucagon / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D010477:Perfusion; D011493:Protein Kinase C / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D000096982:Urea Transporters
D005934:Glucagon; D026901:Membrane Transport Proteins; D011493:Protein Kinase C; D000096982:Urea Transporters