Getting personal: Endogenous adenosine receptor signaling in lymphoblastoid cell lines

J.M. Hillger, C. Diehl, E. van Spronsen, D.I. Boomsma, P.E. Slagboom, L.H. Heitman, A.P. IJzerman

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Genetic differences between individuals that affect drug action form a challenge in drug therapy. Many drugs target G protein-coupled receptors (GPCRs), and a number of receptor variants have been noted to impact drug efficacy. This, however, has never been addressed in a systematic way, and, hence, we studied real-life genetic variation of receptor function in personalized cell lines. As a showcase we studied adenosine A2A receptor (A2AR) signaling in lymphoblastoid cell lines (LCLs) derived from a family of four from the Netherlands Twin Register (NTR), using a non-invasive label-free cellular assay. The potency of a partial agonist differed significantly for one individual. Genotype comparison revealed differences in two intron SNPs including rs2236624, which has been associated with caffeine-induced sleep disorders. While further validation is needed to confirm genotype-specific effects, this set-up clearly demonstrated that LCLs are a suitable model system to study genetic influences on A2AR response in particular and GPCR responses in general.
Original languageEnglish
Pages (from-to)114-122
Number of pages9
JournalBiochemical Pharmacology
Volume115
DOIs
Publication statusPublished - 1 Sep 2016

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