K. Yayama et al., ROLE OF THE KIDNEY IN THE PLASMA-CLEARANCE OF ANGIOTENSINOGEN IN THE RAT - PLASMA-CLEARANCE AND TISSUE DISTRIBUTION OF I-125 ANGIOTENSINOGEN, Life sciences, 57(19), 1995, pp. 1791-1801
Citations number
21
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
We studied the tissue distribution and plasma clearance of angiotensin
ogen (AGN) in rats following an i.v. injection of I-125-labeled AGN. T
he plasma clearance rate of [I-125]AGN fits a two-compartment model wi
th half-lives of 10.2 +/- 1.5 min and 4.1 +/- 0.5 h in non-treated rat
s, and the half-life of slower phase significantly increased to 10.2 /- 1.1 h following bilateral nephrectomy. Radioactivity was predominan
tly distributed in the kidneys (4.9%), and to a lesser extent in the l
iver (1.8%), testis (1.2%), spleen (0.61%), heart (0.35%), lung (0.18%
), thymus (0.03%) and brain (0.03%). The subcellular distribution of r
adioactivity in the kidney was 64% in the soluble fraction and 33% in
the crude mitochondrial-lysosomal fraction. Sodium dodecylsulfate-poly
acrylamide gel electrophoresis revealed that the radioactivity in the
soluble fraction consisted of proteins corresponding to intact [I-125]
AGN, whereas the mitochondrial-lysosomal fraction contained additional
radioactive proteins with molecular weights between 18,000 and 29,000
. When isolated kidney cells were incubated with [I-125]AGN at 0 degre
es C, the radioactive binding was saturable and specific with a Kd val
ue of 4.8 X 10(-11)M, whereas incubation at 37 degrees C resulted in t
he appearance of degraded products of [I-125]AGN in the medium. These
results suggested that circulating AGN is cleared mainly by the kidney
s via receptor-mediated endocytosis, which may play an important role
in regulating plasma level of AGN.