AT1 receptor up-regulation in intestine in chronic renal failure is segment specific.
The role of the AT1 receptor in stimulating colonic K+ secretion was investigated in rats with chronic renal failure (CRF) induced by 5/6 nephrectomy. Compared to control rats, CRF rats up-regulate mucosal AT1 receptors approximately two-fold in the proximal (PC) and distal (DC) colonic segments. In contrast, there was no alteration in AT1 receptor protein mass in jejunal or ileal mucosa. Using 86Rb+ as a tracer for transmural K+ fluxes, a significant stimulation of the basal K+ secretory flux across both PC and DC was observed in vitro and this alteration in K+ transport was temporally correlated with the increase in angiotensin II (ANG II) receptors. In both PC and DC the significant increases in the receptor protein were evident 48 h after partial nephrectomy and they were sustained through 6 weeks. These studies support the hypothesis that CRF-induced secretion of K+ is mediated by an up-regulation of AT1 receptors exclusively in the large intestinal segments.
Hatch
M
M
Department of Medicine, Division of Nephrology, University of California at Irvine, Medical Sciences 1, Rm C380, Irvine, CA 92697, USA. mhatch@uci.edu
Freel
R W
RW
Vaziri
N D
ND
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D003106:Colon / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D007082:Ileum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009392:Nephrectomy; D011188:Potassium / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D015854:Up-Regulation
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D003404:Creatinine; D011188:Potassium