JPET

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


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on February 16, 2005; DOI: 10.1124/jpet.104.081919

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.104.081919v1
313/3/1003    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
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 Guthrie, C. R.
Right arrow Articles by Hamblin, M. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guthrie, C. R.
Right arrow Articles by Hamblin, M. W.


Received for publication December 16, 2004.
Revised February 10, 2005.
Accepted for publication February 10, 2005.

Differential Agonist-Mediated Internalization of the Human 5-HT7 Receptor Isoforms

Chris R. Guthrie 1*, Aaron T. Murray 1, Allyn A. Franklin 1, Mark W. Hamblin 1

1 Veterans Affairs Puget Sound Health Care System

* Address correspondence to: E-mail: cguthrie{at}u.washington.edu

Abstract

The human 5-HT7 serotonin receptor is a class A G-protein coupled receptor that has three isoforms, 5- HT7(a), 5-HT7(b) and 5-HT7(d) , which are produced by alternative splicing. The 5-HT7 receptors are expressed in discrete areas of the brain and in both vascular and gastrointestinal smooth muscle. Central nervous system 5-HT7 receptors may play a role in mood and sleep disorders. 5-HT7 receptors show high affinity for a number of antidepressants and typical and atypical antipsychotics. We report here that the human 5-HT7(d) isoform expressed in HEK 293 cells exhibits a pattern of receptor trafficking in response to agonist that differs from 5-HT7(a) or 5-HT7(b) isoforms. We employed a modification of a live cell labeling technique to demonstrate that surface 5-HT7(d) receptors are constitutively internalized in the absence of agonist. This is in contrast to 5-HT7(a) and 5-HT7(b) isoforms, which do not show this profound agonist-independent internalization. Indeed, the 5-HT7(d) isoform displays this internalization in the presence of a 5-HT7 - specific antagonist. In addition, the human 5-HT7(d) isoform shows a diminished efficacy in stimulation of cAMP-responsive reporter gene activity in transfected cells compared to 5-HT7(a) or 5-HT7(b) receptors expressed at comparable levels. Thus, the carboxy-terminal tail of 5-HT7(d) , which is the longest among known human 5-HT7 isoforms, may contain a motif that interacts with cellular transport mechanisms that is distinct from 5-HT7(a) and 5-HT7(b)


Key words: 5-HT7 receptors, G-protein coupled receptor, immunoflourescence, serotonin, serotonin receptors, trafficking


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
V. P. Pai and N. D. Horseman
Biphasic Regulation of Mammary Epithelial Resistance by Serotonin through Activation of Multiple Pathways
J. Biol. Chem., November 7, 2008; 283(45): 30901 - 30910.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. M. D. Santos, L. A. Gardner, S. W. White, and S. W. Bahouth
Characterization of the Residues in Helix 8 of the Human beta1-Adrenergic Receptor That Are Involved in Coupling the Receptor to G Proteins
J. Biol. Chem., May 5, 2006; 281(18): 12896 - 12907.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
K. W. Andressen, J. H. Norum, F. O. Levy, and K. A. Krobert
Activation of Adenylyl Cyclase by Endogenous Gs-Coupled Receptors in Human Embryonic Kidney 293 Cells Is Attenuated by 5-HT7 Receptor Expression
Mol. Pharmacol., January 1, 2006; 69(1): 207 - 215.
[Abstract] [Full Text] [PDF]


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

Copyright © 2005 by the American Society for Pharmacology and Experimental Therapeutics.