Novel radioiodinated γ-hydroxybutyric acid analogues for radiolabeling and photolinking of high-affinity γ-hydroxybutyric acid binding sites

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Novel radioiodinated γ-hydroxybutyric acid analogues for radiolabeling and photolinking of high-affinity γ-hydroxybutyric acid binding sites. / Wellendorph, Petrine; Høg, Signe; Sabbatini, Paola; Pedersen, Martin Holst Friborg; Martiny, Lars; Knudsen, Gitte Moos; Frølund, Bente Flensborg; Clausen, Rasmus Prætorius; Bräuner-Osborne, Hans.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 335, No. 2, 2010, p. 458-464.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Wellendorph, P, Høg, S, Sabbatini, P, Pedersen, MHF, Martiny, L, Knudsen, GM, Frølund, BF, Clausen, RP & Bräuner-Osborne, H 2010, 'Novel radioiodinated γ-hydroxybutyric acid analogues for radiolabeling and photolinking of high-affinity γ-hydroxybutyric acid binding sites', Journal of Pharmacology and Experimental Therapeutics, vol. 335, no. 2, pp. 458-464. https://doi.org/10.1124/jpet.110.170670

APA

Wellendorph, P., Høg, S., Sabbatini, P., Pedersen, M. H. F., Martiny, L., Knudsen, G. M., ... Bräuner-Osborne, H. (2010). Novel radioiodinated γ-hydroxybutyric acid analogues for radiolabeling and photolinking of high-affinity γ-hydroxybutyric acid binding sites. Journal of Pharmacology and Experimental Therapeutics, 335(2), 458-464. https://doi.org/10.1124/jpet.110.170670

Vancouver

Wellendorph P, Høg S, Sabbatini P, Pedersen MHF, Martiny L, Knudsen GM et al. Novel radioiodinated γ-hydroxybutyric acid analogues for radiolabeling and photolinking of high-affinity γ-hydroxybutyric acid binding sites. Journal of Pharmacology and Experimental Therapeutics. 2010;335(2):458-464. https://doi.org/10.1124/jpet.110.170670

Author

Wellendorph, Petrine ; Høg, Signe ; Sabbatini, Paola ; Pedersen, Martin Holst Friborg ; Martiny, Lars ; Knudsen, Gitte Moos ; Frølund, Bente Flensborg ; Clausen, Rasmus Prætorius ; Bräuner-Osborne, Hans. / Novel radioiodinated γ-hydroxybutyric acid analogues for radiolabeling and photolinking of high-affinity γ-hydroxybutyric acid binding sites. In: Journal of Pharmacology and Experimental Therapeutics. 2010 ; Vol. 335, No. 2. pp. 458-464.

Bibtex

@article{28b78860b74411df825b000ea68e967b,
title = "Novel radioiodinated γ-hydroxybutyric acid analogues for radiolabeling and photolinking of high-affinity γ-hydroxybutyric acid binding sites",
abstract = "gamma-Hydroxybutyric acid (GHB) is a therapeutic drug, a drug of abuse and an endogenous substance that binds to low and high-affinity sites in the mammalian brain. To target the specific GHB binding sites, we have developed a (125)I-labeled GHB analogue and characterized its binding in rat brain homogenate and slices. Our data show that [(125)I]BnOPh-GHB binds to one site in rat brain cortical membranes with low nanomolar affinity (K(d) 7 nM, B(max) 61 pmol/mg protein). The binding is inhibited by GHB and selected analogues, but not by GABA. Autoradiography using horizontal slices from rat brain demonstrates the highest density of binding in hippocampus and cortical regions and the lowest density in the cerebellum. Altogether the findings correlate with the labeling and brain regional distribution of high-affinity GHB sites or [(3)H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([(3)H]NCS-382) binding sites. Using a (125)I-labeled photoaffinity derivative of the new GHB ligand, we have performed denaturing protein electrophoresis and detected one major protein band with an apparent weight of 50 kDa from cortical and hippocampal membranes. [(125)I]BnOPh-GHB is the first reported (125)I-labeled GHB radioligand and is a useful tool for in vitro studies of the specific high-affinity GHB binding sites. The related photoaffinity linker [(125)I]azido-BnOPh-GHB can be used as a probe for isolation of the elusive GHB binding protein.",
keywords = "Faculty of Health and Medical Sciences",
author = "Petrine Wellendorph and Signe H{\o}g and Paola Sabbatini and Pedersen, {Martin Holst Friborg} and Lars Martiny and Knudsen, {Gitte Moos} and Fr{\o}lund, {Bente Flensborg} and Clausen, {Rasmus Pr{\ae}torius} and Hans Br{\"a}uner-Osborne",
year = "2010",
doi = "10.1124/jpet.110.170670",
language = "English",
volume = "335",
pages = "458--464",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

RIS

TY - JOUR

T1 - Novel radioiodinated γ-hydroxybutyric acid analogues for radiolabeling and photolinking of high-affinity γ-hydroxybutyric acid binding sites

AU - Wellendorph, Petrine

AU - Høg, Signe

AU - Sabbatini, Paola

AU - Pedersen, Martin Holst Friborg

AU - Martiny, Lars

AU - Knudsen, Gitte Moos

AU - Frølund, Bente Flensborg

AU - Clausen, Rasmus Prætorius

AU - Bräuner-Osborne, Hans

PY - 2010

Y1 - 2010

N2 - gamma-Hydroxybutyric acid (GHB) is a therapeutic drug, a drug of abuse and an endogenous substance that binds to low and high-affinity sites in the mammalian brain. To target the specific GHB binding sites, we have developed a (125)I-labeled GHB analogue and characterized its binding in rat brain homogenate and slices. Our data show that [(125)I]BnOPh-GHB binds to one site in rat brain cortical membranes with low nanomolar affinity (K(d) 7 nM, B(max) 61 pmol/mg protein). The binding is inhibited by GHB and selected analogues, but not by GABA. Autoradiography using horizontal slices from rat brain demonstrates the highest density of binding in hippocampus and cortical regions and the lowest density in the cerebellum. Altogether the findings correlate with the labeling and brain regional distribution of high-affinity GHB sites or [(3)H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([(3)H]NCS-382) binding sites. Using a (125)I-labeled photoaffinity derivative of the new GHB ligand, we have performed denaturing protein electrophoresis and detected one major protein band with an apparent weight of 50 kDa from cortical and hippocampal membranes. [(125)I]BnOPh-GHB is the first reported (125)I-labeled GHB radioligand and is a useful tool for in vitro studies of the specific high-affinity GHB binding sites. The related photoaffinity linker [(125)I]azido-BnOPh-GHB can be used as a probe for isolation of the elusive GHB binding protein.

AB - gamma-Hydroxybutyric acid (GHB) is a therapeutic drug, a drug of abuse and an endogenous substance that binds to low and high-affinity sites in the mammalian brain. To target the specific GHB binding sites, we have developed a (125)I-labeled GHB analogue and characterized its binding in rat brain homogenate and slices. Our data show that [(125)I]BnOPh-GHB binds to one site in rat brain cortical membranes with low nanomolar affinity (K(d) 7 nM, B(max) 61 pmol/mg protein). The binding is inhibited by GHB and selected analogues, but not by GABA. Autoradiography using horizontal slices from rat brain demonstrates the highest density of binding in hippocampus and cortical regions and the lowest density in the cerebellum. Altogether the findings correlate with the labeling and brain regional distribution of high-affinity GHB sites or [(3)H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([(3)H]NCS-382) binding sites. Using a (125)I-labeled photoaffinity derivative of the new GHB ligand, we have performed denaturing protein electrophoresis and detected one major protein band with an apparent weight of 50 kDa from cortical and hippocampal membranes. [(125)I]BnOPh-GHB is the first reported (125)I-labeled GHB radioligand and is a useful tool for in vitro studies of the specific high-affinity GHB binding sites. The related photoaffinity linker [(125)I]azido-BnOPh-GHB can be used as a probe for isolation of the elusive GHB binding protein.

KW - Faculty of Health and Medical Sciences

U2 - 10.1124/jpet.110.170670

DO - 10.1124/jpet.110.170670

M3 - Journal article

C2 - 20696866

VL - 335

SP - 458

EP - 464

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -

ID: 21772160