Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors

Biochem Biophys Res Commun. 2011 Jan 7;404(1):345-8. doi: 10.1016/j.bbrc.2010.11.121. Epub 2010 Dec 4.


Limonene is a major aromatic compound in essential oils extracted from citrus rind. The application of limonene, especially in aromatherapy, has expanded significantly, but its potential effects on cellular metabolism have been elusive. We found that limonene directly binds to the adenosine A(2A) receptor, which may induce sedative effects. Results from an in vitro radioligand binding assay showed that limonene exhibits selective affinity to A(2A) receptors. In addition, limonene increased cytosolic cAMP concentration and induced activation of protein kinase A and phosphorylation of cAMP-response element-binding protein in Chinese hamster ovary cells transfected with the human adenosine A(2A) receptor gene. Limonene also increased cytosolic calcium concentration, which can be achieved by the activation of adenosine A(2A) receptors. These findings suggest that limonene can act as a ligand and an agonist for adenosine A(2A) receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A2 Receptor Agonists / chemistry*
  • Adenosine A2 Receptor Agonists / metabolism
  • Adenosine A2 Receptor Agonists / pharmacology*
  • Animals
  • Brain / metabolism
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Cyclohexenes / chemistry*
  • Cyclohexenes / metabolism
  • Cyclohexenes / pharmacology*
  • Humans
  • Ligands
  • Limonene
  • Radioligand Assay
  • Rats
  • Receptor, Adenosine A2A / chemistry*
  • Receptor, Adenosine A2A / metabolism
  • Terpenes / chemistry*
  • Terpenes / metabolism
  • Terpenes / pharmacology*


  • Adenosine A2 Receptor Agonists
  • Cyclohexenes
  • Ligands
  • Receptor, Adenosine A2A
  • Terpenes
  • Limonene