JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on March 28, 2003; DOI: 10.1124/jpet.103.051227

0022-3565/03/3061-147-156$20.00
JPET 306:147-156, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.103.051227v1
306/1/147    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Berglund, M. M.
Right arrow Articles by Gehlert, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Berglund, M. M.
Right arrow Articles by Gehlert, D. R.

CELLULAR AND MOLECULAR

The Use of Bioluminescence Resonance Energy Transfer 2 to Study Neuropeptide Y Receptor Agonist-Induced {beta}-Arrestin 2 Interaction

Magnus M. Berglund, Douglas A. Schober, Michael A. Statnick, Patricia H. McDonald, and Donald R. Gehlert

Eli Lilly & Co., Lilly Research Laboratories, LCC, Indianapolis, Indiana (M.M.B., D.A.S., M.A.S., D.R.G.); and Eli Lilly & Co., Sphinx Laboratories, Durham, North Carolina (P.H.D.)

The neuropeptide Y (NPY) family peptides NPY, peptide YY (PYY), and pancreatic polypeptide (PP) bind to four G protein-coupled receptors (GPCRs): Y1, Y2, Y4, and Y5. A key step in the desensitization and internalization of GPCRs is the association of the receptor with {beta}-arrestins. In the present study, these receptors were analyzed with respect to their ability to interact with GFP2-tagged {beta}-arrestin 2 using the new bioluminescence resonance energy transfer 2 method. Agonists induced a concentration-dependent association of {beta}-arrestin 2 with all four receptors. Whereas the Y1 receptor exhibited the highest maximum response and rapid association (t1/2 = 3.4 min), the maximal signals for the association of Y2 and Y4 receptors were less than half of that of Y1, and the association rates were much slower. Interestingly, when evaluated at the Y4 receptor, the Y4 agonist 1229U91 [(Ile,Glu,Pro,Dpr,Tyr,Arg, Leu,Arg,Try-NH2)-2-cyclic(2,4'),(2',4)-diamide] was unable to provoke the same maximal response as human PP, suggesting that 1229U91 is a partial agonist. When stimulated by PYY, the Y5 receptor responded with a t1/2 of 4.6 min and a maximal response approximately 60% of what was observed with Y1. Because {beta}-arrestins are key components in GPCR internalization, it is interesting to note that the receptor that is known to internalize rapidly (Y1) exhibits the most rapid association with {beta}-arrestin 2, whereas the receptor that is known to internalize slowly, or not at all (Y2) associates slowly with {beta}-arrestin 2.

Received for publication March 4, 2003
Accepted March 26, 2003.

Address correspondence to: Dr. Donald R. Gehlert, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285. E-mail: gehlert_donald_r{at}lilly.com




This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
I. R. Tough, N. D. Holliday, and H. M. Cox
Y4 Receptors Mediate the Inhibitory Responses of Pancreatic Polypeptide in Human and Mouse Colon Mucosa
J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 20 - 30.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Marion, R. H. Oakley, K.-M. Kim, M. G. Caron, and L. S. Barak
A beta-Arrestin Binding Determinant Common to the Second Intracellular Loops of Rhodopsin Family G Protein-coupled Receptors
J. Biol. Chem., February 3, 2006; 281(5): 2932 - 2938.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. A. Carter and S. J. Hill
Characterization of Isoprenaline- and Salmeterol-Stimulated Interactions between {beta}2-Adrenoceptors and {beta}-Arrestin 2 Using {beta}-Galactosidase Complementation in C2C12 Cells
J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 839 - 848.
[Abstract] [Full Text] [PDF]

Home page
 J Biomol ScreenHome page
F. F. Hamdan, M. Audet, P. Garneau, J. Pelletier, and M. Bouvier
High-Throughput Screening of G Protein-Coupled Receptor Antagonists Using a Bioluminescence Resonance Energy Transfer 1-Based {beta}-Arrestin2 Recruitment Assay
J Biomol Screen, August 1, 2005; 10(5): 463 - 475.
[Abstract] [PDF]

Home page
 EndocrinologyHome page
K. Bugarith, T. T. Dinh, A.-J. Li, R. C. Speth, and S. Ritter
Basomedial Hypothalamic Injections of Neuropeptide Y Conjugated to Saporin Selectively Disrupt Hypothalamic Controls of Food Intake
Endocrinology, March 1, 2005; 146(3): 1179 - 1191.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
N. D. Holliday, C.-W. Lam, I. R. Tough, and H. M. Cox
Role of the C Terminus in Neuropeptide Y Y Receptor Desensitization and Internalization
Mol. Pharmacol., March 1, 2005; 67(3): 655 - 664.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. M. Berglund, D. A. Schober, M. A. Esterman, and D. R. Gehlert
Neuropeptide Y Y4 Receptor Homodimers Dissociate upon Agonist Stimulation
J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 1120 - 1126.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2003 by the American Society for Pharmacology and Experimental Therapeutics.