![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 60, Issue 5, 1020-1030, November 2001
Departments of Biochemistry (J.A.G., D.J.S, A.B., J.A.W., S.J.H.,
B.L.R.), Psychiatry (B.L.R.), and Neurosciences (B.L.R.), Case Western
Reserve University School of Medicine, Cleveland, Ohio and the Kimmel
Cancer Center (J.L.B.), Thomas Jefferson University Medical School,
Philadelphia, Pennsylvania
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, 
2-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 -adrenergic receptor desensitization. The
cell-type-specific effect of Arr2(319-418) on 5-HT2A
receptor desensitization was not related to the level of GRK2 or GRK5
expression. Interestingly, although 2-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-HT2A
receptor 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
2-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.
This article has been cited by other articles:
|
|
 |
|
  A. Abbas and B. L. Roth Arresting serotonin PNAS, January 22, 2008; 105(3): 831 - 832. [Full Text] [PDF]
|
|
|
|
|
|
C. L. Schmid, K. M. Raehal, and L. M. Bohn From the Cover: Agonist-directed signaling of the serotonin 2A receptor depends on {beta}-arrestin-2 interactions in vivo PNAS, January 22, 2008; 105(3): 1079 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Randhawa, N. A. Farasati, and Y. Huang BK Virus Replication In Vitro: Limited Effect of Drugs Interfering with Viral Uptake and Intracellular Transport Antimicrob. Agents Chemother., December 1, 2007; 51(12): 4492 - 4494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Quan, A. B. McGeachie, D. J. Keating, E. M. van Dam, J. Rusak, N. Chau, C. S. Malladi, C. Chen, A. McCluskey, M. A. Cousin, et al. Myristyl Trimethyl Ammonium Bromide and Octadecyl Trimethyl Ammonium Bromide Are Surface-Active Small Molecule Dynamin Inhibitors that Block Endocytosis Mediated by Dynamin I or Dynamin II Mol. Pharmacol., December 1, 2007; 72(6): 1425 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Harris, H. I. Cohn, S. Pesant, R.-H. Zhou, and A. D. Eckhart Vascular smooth muscle Gq signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3072 - H3079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shi, B. Zemaitaitis, and N. A. Muma Phosphorylation of G{alpha}11 Protein Contributes to Agonist-Induced Desensitization of 5-HT2A Receptor Signaling Mol. Pharmacol., January 1, 2007; 71(1): 303 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cogolludo, L. Moreno, F. Lodi, G. Frazziano, L. Cobeno, J. Tamargo, and F. Perez-Vizcaino Serotonin Inhibits Voltage-Gated K+ Currents in Pulmonary Artery Smooth Muscle Cells: Role of 5-HT2A Receptors, Caveolin-1, and KV1.5 Channel Internalization Circ. Res., April 14, 2006; 98(7): 931 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Barthet, F. Gaven, B. Framery, K. Shinjo, T. Nakamura, S. Claeysen, J. Bockaert, and A. Dumuis Uncoupling and Endocytosis of 5-Hydroxytryptamine 4 Receptors: DISTINCT MOLECULAR EVENTS WITH DIFFERENT GRK2 REQUIREMENTS J. Biol. Chem., July 29, 2005; 280(30): 27924 - 27934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Brackmann, S. Schuchmann, R. Anand, and K.-H. Braunewell Neuronal Ca2+ sensor protein VILIP-1 affects cGMP signalling of guanylyl cyclase B by regulating clathrin-dependent receptor recycling in hippocampal neurons J. Cell Sci., June 1, 2005; 118(11): 2495 - 2505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. J. Bennett, S. A. Perrine, and M. A. Simmons Neurokinin-1 Receptor Resensitization Precedes Receptor Recycling J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1347 - 1354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Clark and J. R. Traynor Endogenous Regulator of G Protein Signaling Proteins Reduce {micro}-Opioid Receptor Desensitization and Down-Regulation and Adenylyl Cyclase Tolerance in C6 Cells J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 809 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Elphick, W. Querbes, J. A. Jordan, G. V. Gee, S. Eash, K. Manley, A. Dugan, M. Stanifer, A. Bhatnagar, W. K. Kroeze, et al. The Human Polyomavirus, JCV, Uses Serotonin Receptors to Infect Cells Science, November 19, 2004; 306(5700): 1380 - 1383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bhatnagar, D. J. Sheffler, W. K. Kroeze, B. Compton-Toth, and B. L. Roth Caveolin-1 Interacts with 5-HT2A Serotonin Receptors and Profoundly Modulates the Signaling of Selected G{alpha}q-coupled Protein Receptors J. Biol. Chem., August 13, 2004; 279(33): 34614 - 34623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Damjanoska, L. D. Van de Kar, G. H. Kindel, Y. Zhang, D. N. D'Souza, F. Garcia, G. Battaglia, and N. A. Muma Chronic Fluoxetine Differentially Affects 5-Hydroxytryptamine2A Receptor Signaling in Frontal Cortex, Oxytocin- and Corticotropin-Releasing Factor-Containing Neurons in Rat Paraventricular Nucleus J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 563 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Xia, J. A. Gray, B. A. Compton-Toth, and B. L. Roth A Direct Interaction of PSD-95 with 5-HT2A Serotonin Receptors Regulates Receptor Trafficking and Signal Transduction J. Biol. Chem., June 6, 2003; 278(24): 21901 - 21908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Gray, A. Bhatnagar, V. V. Gurevich, and B. L. Roth The Interaction of a Constitutively Active Arrestin with the Arrestin-Insensitive 5-HT2A Receptor Induces Agonist-Independent Internalization Mol. Pharmacol., May 1, 2003; 63(5): 961 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. J. Bennett, S. A. Perrine, and M. A. Simmons A Novel Mechanism of Neurokinin-1 Receptor Resensitization J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 1155 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Roth, K. Baner, R. Westkaemper, D. Siebert, K. C. Rice, S. Steinberg, P. Ernsberger, and R. B. Rothman Salvinorin A: A potent naturally occurring nonnitrogenous kappa opioid selective agonist PNAS, September 3, 2002; 99(18): 11934 - 11939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Lowe, J. P. Celver, V. V. Gurevich, and C. Chavkin {micro}-Opioid Receptors Desensitize Less Rapidly than delta -Opioid Receptors Due to Less Efficient Activation of Arrestin J. Biol. Chem., May 3, 2002; 277(18): 15729 - 15735. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
