Degradation and transport of AVP by proximal tubule

Journal Article · Tue Dec 01 04:00:00 EST 1987 · American Journal of Physiology; (USA)

OSTI ID:7191855

Carone, F A; Christensen, E I; Flouret, G ^[1]

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1. Northwestern Univ. Medical School, Chicago, IL (USA) Univ. of Aarhus (Denmark)

High-performance liquid chromatography (HPLC) analysis revealed that (3,4,5-{sup 3}H-Phe{sup 3},Arg{sup 8})vasopressin (({sup 3}H)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, ({sup 3}H)AVP was degraded by both preparations. Renal cortical homogenates in vitro and luminal peptidases of proximal tubule in vivo degraded ({sup 3}H)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 ({sup 3}H)Phe by tubular aminopeptidases. Following microinfusion of ({sup 3}H)AVP into proximal tubules, 15.7% of the label was absorbed. Five and fifteen minutes after infusion of ({sup 3}H)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.

• OSTI ID: 7191855
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 253:6; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AUTORADIOGRAPHY
BIODEGRADATION
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BIOSYNTHESIS
BODY
BODY FLUIDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
CHROMATOGRAPHY
DECOMPOSITION
DRUGS
ELECTRON MICROSCOPY
ENZYMATIC HYDROLYSIS
GLUTATHIONE
HORMONES
HYDROGEN COMPOUNDS
HYDROLYSIS
KIDNEYS
LIQUID COLUMN CHROMATOGRAPHY
LYSIS
LYSOSOMES
MAMMALS
MATERIALS
MEMBRANE TRANSPORT
MICROSCOPY
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PEPTIDE HORMONES
PEPTIDES
PITUITARY HORMONES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SEPARATION PROCESSES
SOLVOLYSIS
SYNTHESIS
TRANSMISSION ELECTRON MICROSCOPY
TRITIUM COMPOUNDS
TUBULES
URINE
VASOPRESSIN
VERTEBRATES
WASTES