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- Title
Selective Reduction in A<sub>2</sub> Adenosine Receptor Desensitization Following Antisense-Induced Suppression of G Protein-Coupled Receptor Kinase 2 Expression.
- Authors
Willets, Jonathon M; Parent, Jean-Luc; Benovic, Jeffrey L; Kelly, Eamonn
- Abstract
Abstract: Phosphorylation of G protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) is considered to play a critical role in the desensitization of responses mediated by these receptors. To explore the role of GRK2 in A[sub 2] adenosine receptor desensitization, we attempted to reduce specifically GRK2 expression in NG108-15 cells by stable transfection with an antisense rat GRK2 cDNA sequence. This yielded up to a 69% loss of GRK2 when compared with plasmid-transfected control cells, which correlated with a reduction in kinase activity when measured by the ability of cell lysates to promote light-dependent phosphorylation of rhodopsin. Levels of GRK3 were the same in antisense and plasmid-transfected controls. On addition of the A[sub 2] adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine, cyclic AMP accumulation was greater in GRK2 antisense cells as compared with plasmid control cells. In contrast, cyclic AMP accumulation via agonist stimulation of either IP-prostanoid or secretin receptors or by addition of forskolin was not significantly different among all clones examined. The increase in A[sub 2] adenosine receptor response could not be explained by changes in A[sub 2A] adenosine receptor expression, as assessed by ligand binding experiments with the radioligand 2-[sup 3]H-labelled 4-[2-[7-amino -2-(2-fu ryl)[1,2,4]t riazolo[2,3-a][1,3,5]t riazin-5-ylamino]ethyl]phenol ([[sup 3]H]ZM241385). These data show for the first time a direct correlation between expression of GRK2 and desensitization of natively...
- Subjects
PHOSPHORYLATION; G proteins; PROTEIN kinases; RHODOPSIN
- Publication
Journal of Neurochemistry, 1999, Vol 73, Issue 5, p1781
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.1999.0731781.x