L-amino acids regulate parathyroid hormone secretion.
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.
Conigrave
Arthur D
AD
School of Molecular and Microbial Biosciences, University of Sydney, New South Wales 2006, Australia. a.conigrave@mmb.usyd.edu
Mun
Hee-Chang
HC
Delbridge
Leigh
L
Quinn
Stephen J
SJ
Wilkinson
Margaret
M
Brown
Edward M
EM
D000596:Amino Acids / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007477:Ions; D008274:Magnesium / Q000378:metabolism; D010280:Parathyroid Glands / Q000166:cytology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism*; D010649:Phenylalanine / Q000737:chemistry; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D012680:Sensitivity and Specificity; D013096:Spermine / Q000378:metabolism; D013997:Time Factors; D014364:Tryptophan / Q000737:chemistry
D000596:Amino Acids; D007477:Ions; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D013096:Spermine; D010649:Phenylalanine; D014364:Tryptophan; D008274:Magnesium; D002118:Calcium