Document Detail

Effects of D-amino acid substituents on degradation of LHRH analogues by proximal tubule.
MedLine Citation:
PMID:  3548429     Owner:  NLM     Status:  MEDLINE    
Less than Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, the luteinizing hormone-releasing hormone, LHRH, is degraded in renal proximal tubules (PT) in vivo (rat) and in vitro (rabbit) to less than Glu-His (2), less than Glu-His-Trp (3), and less than Glu-His-Trp-Ser (4). LHRH may be cleaved by endopeptidases simultaneously at multiple bonds, or initially at Ser4-Tyr5 followed by carboxypeptidase hydrolysis of 4 to 3 and then 2. To distinguish between these mechanisms, [3H]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-Ser4]LHRH was not cleaved at D Ser4-Tyr5 but yielded less than Glu-His-Trp-D-Ser-Tyr-Gly as the major metabolite plus 2 and 3. [D-Trp6]LHRH was cleaved by BBM and PT to 2 and 3, but not to 4. [D-Ser4, D-Trp6]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. [3H]LHRH was cleaved by BBM or by endopeptidase-24.11 from porcine PT to metabolites 2, 4, small amounts of 3, and less than Glu-His-Trp-Ser-Tyr-Gly, but cleavage was strongly inhibited by the specific inhibitor phosphoramidon. 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 known cleavage site.
G Flouret; T Majewski; D R Peterson; A J Kenny; F A Carone
Related Documents :
11553759 - Hormonal changes in the grains of rice subjected to water stress during grain filling.
6318849 - Inhibition of lipogenesis by vasopressin and angiotensin ii in glycogen-depleted hepato...
11288979 - Reassessment of the location of the thyrotropin receptor 50 amino acid "insertion" prov...
5356549 - Proteins and insulin release: a dual role of amino-acids and intestinal hormones.
125309 - The production of cardiac hypertrophy by tri-iodothyroacetic acid.
12093449 - Use of amino acids as growth hormone-releasing agents by athletes.
7171539 - Effect of diet and infusion of volatile fatty acids into the rumen on the concentration...
8605979 - Inversion of configuration during hydrolysis of alpha-1,4-galacturonidic linkage by thr...
1938199 - Proximal gastric vagotomy. a comparative study between the standard technique and the e...
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  252     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1987 Mar 
Date Detail:
Created Date:  1987-04-16     Completed Date:  1987-04-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  E320-6     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amino Acid Sequence
Amino Acids / metabolism
Endopeptidases / metabolism
Gonadotropin-Releasing Hormone / metabolism*
Hormones / metabolism
Kidney Tubules, Proximal / metabolism*
Microvilli / metabolism
Structure-Activity Relationship
Substrate Specificity
Grant Support
Reg. No./Substance:
0/Amino Acids; 0/Hormones; 33515-09-2/Gonadotropin-Releasing Hormone; EC 3.4.-/Endopeptidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Role of acidosis in regulating hepatic nitrogen metabolism during fasting in conscious dog.
Next Document:  Membrane currents of identified isolated rat corticotropes and gonadotropes.