RT Journal Article
SR Electronic
T1 Cell-Type Specific Effects of Endocytosis Inhibitors on  5-Hydroxytryptamine<sub>2A</sub> Receptor Desensitization and Resensitization Reveal an Arrestin-, GRK2-, and  GRK5-Independent Mode of Regulation in Human  Embryonic Kidney 293 Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1020
OP 1030
DO 10.1124/mol.60.5.1020
VO 60
IS 5
A1 Gray, John A.
A1 Sheffler, Douglas J.
A1 Bhatnagar, Anushree
A1 Woods, Jason A.
A1 Hufeisen, Sandra J.
A1 Benovic, Jeffrey L.
A1 Roth, Bryan L.
YR 2001
UL http://molpharm.aspetjournals.org/content/60/5/1020.abstract
AB The effect of endocytosis inhibitors on 5-hydroxytryptamine2A (5-HT2A) receptor desensitization and resensitization was examined in transiently transfected human embryonic kidney (HEK) 293 cells and in C6 glioma cells that endogenously express 5-HT2A receptors. In HEK-293 cells, 5-HT2A receptor desensitization was unaffected by cotransfection with a dominant-negative mutant of dynamin (DynK44A), a truncation mutant of arrestin-2 [Arr2(319–418)], or by two well-characterized chemical inhibitors of endocytosis: concanavalin A (conA) and phenylarsine oxide (PAO). In contrast, β2-adrenergic receptor desensitization was significantly potentiated by each of these treatments in HEK-293 cells. In C6 glioma cells, however, DynK44A, Arr2(319–418), conA, and PAO each resulted in the potentiation of 5-HT2A and β-adrenergic receptor desensitization. The cell-type-specific effect of Arr2(319–418) on 5-HT2Areceptor desensitization was not related to the level of GRK2 or GRK5 expression. Interestingly, although β2-adrenergic receptor resensitization was potently blocked by cotransfection with DynK44A, 5-HT2A receptor resensitization was enhanced, suggesting the existence of a novel cell-surface mechanism for 5-HT2Areceptor resensitization in HEK-293 cells. In addition, Arr2(319–418) had no effect on 5-HT2A receptor resensitization in HEK-293 cells, although it attenuated the resensitization of the β2-adrenergic receptor. However, in C6 glioma cells, both DynK44A and Arr2(319–418) significantly reduced 5-HT2A receptor resensitization. Taken together, these results provide the first convincing evidence of cell-type-specific roles for endocytosis inhibitors in regulating GPCR activity. Additionally, these results imply that novel GRK and arrestin-independent mechanisms of 5-HT2A receptor desensitization and resensitization exist in HEK-293 cells.