Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B

Yoko Irukayama-Tomobe, Hirokazu Tanaka, Takehiko Yokomizo, Tomomi Hashidate-Yoshida, Masashi Yanagisawa, Takeshi Sakurai

Research output: Contribution to journalArticle

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Abstract

GPR109B (HM74) is a putative G protein-coupled receptor (GPCR) whose cognate ligands have yet to be characterized. GPR109B shows a high degree of sequence similarity to GPR109A, another GPCR that was identified as a high-affinity nicotinic acid (niacin) receptor. However, the affinity of nicotinic acid to GPR109B is very low. In this study, we found that certain aromatic D-amino acids, including D-phenylalanine, D-tryptophan, and the metabolite of the latter, D-kynurenine, decreased the activity of adenylate cyclase in cells transfected with GPR109B cDNA through activation of pertussis toxin (PTX)-sensitive G proteins. These D-amino acids also elicited a transient rise of intracellular Ca2+ level in cells expressing GPR109B in a PTX-sensitive manner. In contrast, these D-amino acids did not show any effects on cells expressing GPR109A. We found that the GPR109B mRNA is abundantly expressed in human neutrophils. D-phenylalanine and D-tryptophan induced a transient increase of intracellular Ca2+ level and a reduction of cAMP levels in human neutrophils. Furthermore, knockdown of GPR109B by RNA interference inhibited the D-amino acids-induced decrease of cellular cAMP levels in human neutrophils. These D-amino acids induced chemotactic activity of freshly prepared human neutrophils. We also found that D-phenylalanine and D-tryptophan induced chemotactic responses in Jurkat cells transfected with the GPR109B cDNA but not in mock-transfected Jurkat cells. These results suggest that these aromatic D-amino acids elicit a chemotactic response in human neutrophils via activation of GPR109B.

Original languageEnglish (US)
Pages (from-to)3930-3934
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number10
DOIs
StatePublished - Mar 10 2009

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Keywords

  • D-kynurenine
  • D-phenylalanine
  • D-tryptophan
  • Nicotinic acid (niacin)
  • Orphan receptor

ASJC Scopus subject areas

  • General

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