Document Detail


L-amino acids regulate parathyroid hormone secretion.
MedLine Citation:
PMID:  15234970     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Parathyroid hormone (PTH) secretion is acutely regulated by the extracellular Ca(2+)-sensing receptor (CaR). Thus, Ca(2+) ions, and to a lesser extent Mg(2+) ions, have been viewed as the principal physiological regulators of PTH secretion. Herein we show that in physiological concentrations, l-amino acids acutely and reversibly activated the extracellular Ca(2+)-sensing receptor in normal human parathyroid cells and inhibited parathyroid hormone secretion. Individual l-amino acids, especially of the aromatic and aliphatic classes, as well as plasma-like amino acid mixtures, stereoselectively mobilized Ca(2+) ions in normal human parathyroid cells in the presence but not the absence of the CaR agonists, extracellular Ca(2+) (Ca(2+)(o)), or spermine. The order of potency was l-Trp = l-Phe > l-His > l-Ala > l-Glu > l-Arg = l-Leu. CaR-active amino acids also acutely and reversibly suppressed PTH secretion at physiological ionized Ca(2+) concentrations. At a Ca(2+)(o) of 1.1 mm and an amino acid concentration of 1 mm, CaR-active amino acids (l-Phe = l-Trp > l-His = l-Ala), but not CaR-inactive amino acids (l-Leu and l-Arg), stereoselectively suppressed PTH secretion by up to 40%, similar to the effect of raising Ca(2+)(o) to 1.2 mm. A physiologically relevant increase in the -fold concentration of the plasma-like amino acid mixture (from 1x to 2x) also reversibly suppressed PTH secretion in the Ca(2+)(o) concentration range 1.05-1.25 mm. In conclusion, l-amino acids acutely and reversibly activate endogenous CaRs and suppress PTH secretion at physiological concentrations. The results indicate that l-amino acids are physiological regulators of PTH secretion and thus whole body calcium metabolism.
Authors:
Arthur D Conigrave; Hee-Chang Mun; Leigh Delbridge; Stephen J Quinn; Margaret Wilkinson; Edward M Brown
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-07-02
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-06     Completed Date:  2004-10-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  38151-9     Citation Subset:  IM    
Affiliation:
School of Molecular and Microbial Biosciences, University of Sydney, New South Wales 2006, Australia. a.conigrave@mmb.usyd.edu
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / metabolism*
Calcium / metabolism
Cytoplasm / metabolism
Dose-Response Relationship, Drug
Humans
Ions
Magnesium / metabolism
Parathyroid Glands / cytology,  metabolism
Parathyroid Hormone / secretion*
Phenylalanine / chemistry
Receptors, Calcium-Sensing / metabolism
Sensitivity and Specificity
Spermine / metabolism
Time Factors
Tryptophan / chemistry
Grant Support
ID/Acronym/Agency:
DK41415/DK/NIDDK NIH HHS; DK48330/DK/NIDDK NIH HHS; DK52005/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Ions; 0/Parathyroid Hormone; 0/Receptors, Calcium-Sensing; 63-91-2/Phenylalanine; 71-44-3/Spermine; 73-22-3/Tryptophan; 7439-95-4/Magnesium; 7440-70-2/Calcium

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


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