AJP - Renal Physiology, Vol 253, Issue 6 1120-F1128, Copyright © 1987 by American Physiological Society
Degradation and transport of AVP by proximal tubule
F. A. Carone, E. I. Christensen and G. Flouret
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611.
High-performance liquid chromatography (HPLC) analysis revealed that
[3,4,5-3H-Phe3,Arg8]vasopressin ([3H]AVP) was not degraded by isolated
renal brush-border membranes or by a cortical lysosomal fraction in vitro;
however, in the presence of 1 mM reduced glutathione, [3H]AVP was degraded
by both preparations. Renal cortical homogenates in vitro and luminal
peptidases of proximal tubule in vivo degraded [3H]AVP and in both
instances yielded phenylalanine, hexapeptide AVP 1-6, heptapeptide AVP 1-7,
octapeptide AVP 1-8, and two uncharacterized products X and Y. These data
suggest that filtered AVP is reduced in the proximal tubule by a reduced
glutathione-dependent transhydrogenase and subsequently cleaved to [3H]Phe
by tubular aminopeptidases. Following microinfusion of [3H]AVP into
proximal tubules, 15.7% of the label was absorbed. Five and fifteen minutes
after infusion of [3H]AVP, sequestration of total label in proximal tubules
was 4.5 and 2.1%, respectively, and quantitative electron microscope
autoradiography revealed accumulation of grains over apical endocytic
vacuoles and lysosomes consistent with endocytic uptake and rapid lysosomal
degradation of AVP and/or a large metabolite. Thus, enzymatic cleavage of
AVP by luminal and lysosomal peptidases in proximal tubules could involve
disulfide bond, C-terminal, and N-terminal loci.
