Getting personal: Endogenous adenosine receptor signaling in lymphoblastoid cell lines.
Biochem Pharmacol
; 115: 114-22, 2016 09 01.
Article
em En
| MEDLINE
| ID: mdl-27297283
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.
Palavras-chave
Adenosine (PubChem CID: 60961); Adenosine A(2A) receptor; BAY60-6583 (PubChem CID: 11717831); CCPA (PubChem CID: 123807); CGS21680 (PubChem CID: 3086599); Cl-IB-MECA (PubChem CID: 3035850); G protein-coupled receptors; Istradefylline (PubChem CID: 5311037); LUF5448 (PubChem CID: 69538223); Label-free; Lymphoblastoid cell lines; NECA (PubChem CID: 448222); Precision medicine; Single Nucleotide Polymorphism; ZM241385 (PubChem CID: 176407)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Transdução de Sinais
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Receptor A2A de Adenosina
Limite:
Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Holanda