| Effects of D-amino acid substituents on degradation of LHRH analogues by proximal tubule. | |
| | |
MedLine Citation:
|
PMID: 3548429 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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 | |
Descriptor/Qualifier:
|
Amino Acid Sequence Amino Acids / metabolism Animals Endopeptidases / metabolism Gonadotropin-Releasing Hormone / metabolism* Hormones / metabolism Kidney Tubules, Proximal / metabolism* Microvilli / metabolism Rabbits Rats Structure-Activity Relationship Substrate Specificity |
| Grant Support | |
ID/Acronym/Agency:
|
AM-14610/AM/NIADDK NIH HHS; AM-27646/AM/NIADDK NIH HHS; HD-08669/HD/NICHD NIH HHS |
| Chemical | |
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.