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Characterization of the effects of four HTR3B polymorphisms an human 5-HT3AB receptor expression and signalling

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Characterization of the effects of four HTR3B polymorphisms an human 5-HT3AB receptor expression and signalling. / Krzywkowski, Karen; Davies, Paul A.; Irving, Andrew J.; Brauner-Osborne, Hans; Jensen, Anders A.

In: Pharmacogenetics and Genomics, Vol. 18, No. 12, 12.2008, p. 1027-1040.

Research output: Contribution to journalArticle

Harvard

Krzywkowski, K, Davies, PA, Irving, AJ, Brauner-Osborne, H & Jensen, AA 2008, 'Characterization of the effects of four HTR3B polymorphisms an human 5-HT3AB receptor expression and signalling' Pharmacogenetics and Genomics, vol 18, no. 12, pp. 1027-1040., 10.1097/FPC.0b013e328310f950

APA

Krzywkowski, K., Davies, P. A., Irving, A. J., Brauner-Osborne, H., & Jensen, A. A. (2008). Characterization of the effects of four HTR3B polymorphisms an human 5-HT3AB receptor expression and signalling. Pharmacogenetics and Genomics, 18(12), 1027-1040. 10.1097/FPC.0b013e328310f950

Vancouver

Krzywkowski K, Davies PA, Irving AJ, Brauner-Osborne H, Jensen AA. Characterization of the effects of four HTR3B polymorphisms an human 5-HT3AB receptor expression and signalling. Pharmacogenetics and Genomics. 2008 Dec;18(12):1027-1040. Available from: 10.1097/FPC.0b013e328310f950

Author

Krzywkowski, Karen; Davies, Paul A.; Irving, Andrew J.; Brauner-Osborne, Hans; Jensen, Anders A. / Characterization of the effects of four HTR3B polymorphisms an human 5-HT3AB receptor expression and signalling.

In: Pharmacogenetics and Genomics, Vol. 18, No. 12, 12.2008, p. 1027-1040.

Research output: Contribution to journalArticle

Bibtex - Download

@article{32ab8cc0769745768f38bb57145d6e48,
title = "Characterization of the effects of four HTR3B polymorphisms an human 5-HT3AB receptor expression and signalling",
keywords = "5-HT3A, 5-HT3AB, 5-HT3B, expression, function, ligand-gated ion channel, polymorphism, serotonin, single-nucleotide polymorphism, variant, NICOTINIC ACETYLCHOLINE-RECEPTORS, SEROTONIN-RECEPTOR, MAJOR DEPRESSION, HUMAN GENOME, SUBUNIT, GENE, 5-HYDROXYTRYPTAMINE, CHANNEL, HETEROGENEITY, MUTATIONS",
author = "Karen Krzywkowski and Davies, {Paul A.} and Irving, {Andrew J.} and Hans Brauner-Osborne and Jensen, {Anders A.}",
year = "2008",
doi = "10.1097/FPC.0b013e328310f950",
volume = "18",
number = "12",
pages = "1027--1040",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Characterization of the effects of four HTR3B polymorphisms an human 5-HT3AB receptor expression and signalling

A1 - Krzywkowski,Karen

A1 - Davies,Paul A.

A1 - Irving,Andrew J.

A1 - Brauner-Osborne,Hans

A1 - Jensen,Anders A.

AU - Krzywkowski,Karen

AU - Davies,Paul A.

AU - Irving,Andrew J.

AU - Brauner-Osborne,Hans

AU - Jensen,Anders A.

PY - 2008/12

Y1 - 2008/12

N2 - <p>Background 5-Hydroxytryptamine 3 (5-HT3) receptors mediate the fast excitatory neurotransmission of serotonin. In this study, we have characterized the effects of four naturally occurring, nonsynonymous variants of the human 5-HT3B subunit on expression and signalling properties of heteromeric 5-HT3AB receptors.</p><p>Methods and results 5-HT3AB receptor signalling was studied in a fluorescence-based cell membrane potential assay and by electrophysiology. Expression levels of cotransfected epitope-tagged 5-HT3A and 5-HT3B subunits were determined using enzyme-linked immunosorbent assay and immunocytochemistry. In cells coexpressing 5-HT3A and 5-HT3B(I143T) subunits, cell surface expression levels of 5-HT3B in particular, and also 5-HT3A were markedly reduced compared with those of wild-type (WT) 5-HT3AB receptor-expressing cells. Electrophysiological recordings on cells coexpressing 5-HT3A and 5-HT3B(I143T) indicated cell surface expression of 5-HT3AB(1143T) receptors with macroscopic current kinetics similar to those of WT 5-HT3AB receptors but with 3-fold lower current densities. In the membrane potential assay, 5-HT3AB(I143T)-transfected cells exhibited signalling properties intermediate to those of WT 5-HT3AB and 5-HT3A receptors. Cotransfection of 5-HT3A, 5-HT3AB(I143T) and WT 5-HT3AB subunit cDNAs did not increase cell surface expression of the variant subunit nor did it restore WT 5-HT3AB receptor signalling completely in the membrane potential assay. In contrast to 5-HT3B(I143T), the 5-HT3B variants S1 56R, V183I and A223T did not give rise to significant changes in 5-HT3AB receptor expression or signalling properties.</p><p>Conclusion 5-HT3B(I143T)-containing 5-HT3AB receptors display significantly reduced cell surface expression and different signalling properties compared with WT 5-HT3AB receptors. In contrast, three other 5-HT3B variants, S156R, V183I and A223T, do not appear to alter 5-HT3AB receptor expression or signalling. Pharmacogenetics and Genomics 18:1027-1040 (C) 2008 Wolters Kluwer Health | Lippincott Williams &amp; Wilkins.</p>

AB - <p>Background 5-Hydroxytryptamine 3 (5-HT3) receptors mediate the fast excitatory neurotransmission of serotonin. In this study, we have characterized the effects of four naturally occurring, nonsynonymous variants of the human 5-HT3B subunit on expression and signalling properties of heteromeric 5-HT3AB receptors.</p><p>Methods and results 5-HT3AB receptor signalling was studied in a fluorescence-based cell membrane potential assay and by electrophysiology. Expression levels of cotransfected epitope-tagged 5-HT3A and 5-HT3B subunits were determined using enzyme-linked immunosorbent assay and immunocytochemistry. In cells coexpressing 5-HT3A and 5-HT3B(I143T) subunits, cell surface expression levels of 5-HT3B in particular, and also 5-HT3A were markedly reduced compared with those of wild-type (WT) 5-HT3AB receptor-expressing cells. Electrophysiological recordings on cells coexpressing 5-HT3A and 5-HT3B(I143T) indicated cell surface expression of 5-HT3AB(1143T) receptors with macroscopic current kinetics similar to those of WT 5-HT3AB receptors but with 3-fold lower current densities. In the membrane potential assay, 5-HT3AB(I143T)-transfected cells exhibited signalling properties intermediate to those of WT 5-HT3AB and 5-HT3A receptors. Cotransfection of 5-HT3A, 5-HT3AB(I143T) and WT 5-HT3AB subunit cDNAs did not increase cell surface expression of the variant subunit nor did it restore WT 5-HT3AB receptor signalling completely in the membrane potential assay. In contrast to 5-HT3B(I143T), the 5-HT3B variants S1 56R, V183I and A223T did not give rise to significant changes in 5-HT3AB receptor expression or signalling properties.</p><p>Conclusion 5-HT3B(I143T)-containing 5-HT3AB receptors display significantly reduced cell surface expression and different signalling properties compared with WT 5-HT3AB receptors. In contrast, three other 5-HT3B variants, S156R, V183I and A223T, do not appear to alter 5-HT3AB receptor expression or signalling. Pharmacogenetics and Genomics 18:1027-1040 (C) 2008 Wolters Kluwer Health | Lippincott Williams &amp; Wilkins.</p>

KW - 5-HT3A

KW - 5-HT3AB

KW - 5-HT3B

KW - expression

KW - function

KW - ligand-gated ion channel

KW - polymorphism

KW - serotonin

KW - single-nucleotide polymorphism

KW - variant

KW - NICOTINIC ACETYLCHOLINE-RECEPTORS

KW - SEROTONIN-RECEPTOR

KW - MAJOR DEPRESSION

KW - HUMAN GENOME

KW - SUBUNIT

KW - GENE

KW - 5-HYDROXYTRYPTAMINE

KW - CHANNEL

KW - HETEROGENEITY

KW - MUTATIONS

U2 - 10.1097/FPC.0b013e328310f950

DO - 10.1097/FPC.0b013e328310f950

M1 - Article

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 12

VL - 18

SP - 1027

EP - 1040

ER -

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