Effects of D-amino acid substituents on degradation of LHRH analogues by proximal tubule

Journal Article · Sun Mar 01 00:00:00 EST 1987 · Am. J. Physiol.; (United States)

OSTI ID:5445418

Flouret, G; Majewski, T; Peterson, D R; Kenny, A J; Carone, F A

The luteinizing hormone-releasing hormone, LHRH, is degraded in renal proximal tubules (PT) in vivo (rat) and in vitro (rabbit) to < Glu-His (2), < Glu-His-Trp (3), and < Glu-His-Trp-Ser (4). LHRH may be cleaved by endopeptidases simultaneously at multiple bonds, or initially at Ser/sup 4/-Try/sup 5/ followed by carboxypeptidase hydrolysis of 4 to 3 and then 2. To distinguish between these mechanisms, (/sup 3/H)LHRH analogues were incubated with rabbit renal brush-border membranes (BBM), microinfused into PT in vivo or in vitro, and products were analyzed by HPLC. (D-Ser/sup 4/)LHRH was not cleaved at D-Ser/sup 4/-Try/sup 5/ but yielded < Glu-His-Trp-D-Ser-Tyr-Gly as the major metabolite plus 2 and 3. (D-Trp/sup 6/)LHRH was cleaved by BBM and PT to 2 and 3, but not to 4. (D-Ser/sup 4/, D-Trp/sup 6/)LHRH was not cleaved by BBM, but was degraded to 2 by PT in vivo. Thus, D-amino acid substituents altered the expected cleavage pattern of these analogues. Thus, normally LHRH may be cleaved in PT by endopeptidase-24.11 to 2 and 4, and by angiotensin I-converting enzyme to 3, its know cleavage site.

• Research Organization: Northwestern Univ. Medical School, Chicago, IL
• OSTI ID: 5445418
• Journal Information: Am. J. Physiol.; (United States), Vol. 252:3
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
LH-RH
BIODEGRADATION
TRITIUM COMPOUNDS
AMINO ACIDS
ANGIOTENSIN
IN VITRO
IN VIVO
KIDNEYS
LIQUID COLUMN CHROMATOGRAPHY
PEPTIDE HYDROLASES
RABBITS
RATS
TUBULES
ANIMALS
BODY
CARBOXYLIC ACIDS
CARDIOVASCULAR AGENTS
CHEMICAL REACTIONS
CHROMATOGRAPHY
DECOMPOSITION
DRUGS
ENZYMES
GLOBULINS
HORMONES
HYDROLASES
LABELLED COMPOUNDS
LIBERINS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
PROTEINS
RODENTS
SEPARATION PROCESSES
VASOCONSTRICTORS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques