QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.081919v1 313/3/1003    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guthrie, C. R. Articles by Hamblin, M. W. Search for Related Content PubMed PubMed Citation Articles by Guthrie, C. R. Articles by Hamblin, M. W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

CELLULAR AND MOLECULAR

Differential Agonist-Mediated Internalization of the Human 5-Hydroxytryptamine 7 Receptor Isoforms

Veteran's Affairs Puget Sound Health Care System, Seattle, Washington (C.R.G., A.T.M., A.A.F., M.W.H.); and Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington (M.W.H.)

The human 5-hydroxytryptamine 7 (5-HT₇) serotonin receptor is a class A G-protein coupled receptor that has three isoforms, 5-HT_7(a), 5-HT_7(b), and 5-HT_7(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-HT_7(d) isoform expressed in human embryonic kidney (HEK) 293 cells exhibits a pattern of receptor trafficking in response to agonist that differ from 5-HT_7(a) or 5-HT_7(b) isoforms. We employed a modification of a live cell-labeling technique to demonstrate that surface 5-HT_7(d) receptors are constitutively internalized in the absence of agonist. This is in contrast to 5-HT_7(a) and 5-HT_7(b) isoforms, which do not show this profound agonist-independent internalization. Indeed, the 5-HT_7(d) isoform displays this internalization in the presence of a 5-HT₇ -specific antagonist. In addition, the human 5-HT₇ isoform shows a diminished efficacy in stimulation of cAMP-responsive reporter gene activity in transfected cells compared with 5-HT_7(a) or 5-HT_7(b) receptors expressed at comparable levels. Thus, the carboxy-terminal tail of 5-HT_7(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-HT_7(a) and 5-HT_7(b).

Address correspondence to: Chris R. Guthrie, Veterans Affairs Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108. E-mail: cguthrie{at}u.washington.edu

This article has been cited by other articles:

				R. Lu, Y. Li, Y. Zhang, Y. Chen, A. D. Shields, D. G. Winder, T. Angelotti, K. Jiao, L. E. Limbird, Y. Zhou, et al. Epitope-tagged Receptor Knock-in Mice Reveal That Differential Desensitization of {alpha}2-Adrenergic Responses Is because of Ligand-selective Internalization J. Biol. Chem., May 8, 2009; 284(19): 13233 - 13243. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]