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General information

Name (center, department, group or other)
Wellendorph lab, Section for Experimental Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen
Contact name
Petrine Wellendorph
Contact email
pw#at#sund#dot#ku#dot#dk
Contact title
Associate Professor
Date
10. December 2015
(Last edited: 10. December 2015)

Brief description of research activities

Dr. Wellendorph’s laboratory is part of the Experimental Pharmacology Section at the Department of Drug Design and Pharmacology at the University of Copenhagen. The focus of the laboratory is the molecular characterization of transporters and receptors for the main inhibitory neurotransmitter GABA in the mammalian central nervous system, aimed at understanding the role of these membrane proteins as novel drug targets. One major project concerns t he chemical works of g-hydroxybutyric acid (GHB) in the brain, currently funded through a Lundbeck Foundation Fellowship (2013). Using selective GHB analogues the project aims to identify and characterize the molecular targets for GHB by different biochemical and pharmacological methods, and the novel finding that GHB activates subclasses of ionotropic GABA-A receptors. Another major project concerns the molecular characterization of GABA transporters using selective tool compounds. The line of research combines expertises in pharmacology, medicinal chemistry and neurobiology and includes facilities for conducting state-of-the-art molecular biology, cell culturing, pharmacological assaying, two-electode voltage clamp and patch-clamp electrophysiology, radioligand binding/autoradiography studies and expression studies (immunochemistry and qPCR studies).

Keywords

Drug targets GABA receptors and transporters
GABA GHB/Fantasy Inhibitory neurotransmission
Molecular pharmacology
Structure-acttivity relationships
photoaffinity labelling
proteomics
Genetically modified mice

Research tools and techniques

cell-based pharmacological assays
electrophysiology
radioligand binding techniques
label-free assays
molecular biology and cloning

Scientific Personnel

No of Associate Professors/Postdocs: 3
No of PhD students: 3
Other: 3

Key references from within the last 5 years

Damgaard M, Al-Khawaja A, Vogensen SB, Jurik A, Sijm M, Lie ME, Bæk MI, Rosenthal E, Jensen AA, Ecker GF, Frølund B, Wellendorph P, Clausen RP (2015). Identification of the first highly subtype-selective inhibitor of human GABA transporter GAT3. ACS Chem Neurosci. 6:1591-9.
Thiesen L, Kehler J, Clausen RP, Frølund B, Bundgaard C, Wellendorph P. In vitro and in vivo evidence for active brain uptake of the GHB analog HOCPCA by the monocarboxylate transporter subtype 1 (2015). J. Pharmacol. Exp. Ther. 354: 166-74.

Al-Khawaja A, Petersen, JG, Damgaard M, Jensen, MH, Vogensen SB, Lie MEK, Kragholm B, Bräuner-Osborne H, Clausen RP, Frølund B, Wellendorph P* (2014). Pharmacological identification of a guanidine-containing β-alanine analogue with low micromolar potency and selectivity for the betaine/GABA transporter 1 (BGT1). Neurchem. Res. 39: 1988-96.

Bay T, Eghorn LF, Klein AB & Wellendorph P* (2014). GHB receptor targets in the CNS: Focus on high-affinity binding sites. Biochem Pharmacol; 87: 220-8.

Eghorn LF, Hoestgaard-Jensen K, Kongstad KT, Bay T, Higgins D, Frølund B, Wellendorph P (2014). Positive allosteric modulation of the GHB high-affinity binding site by the GABAA receptor modulator monastrol and the flavonoid catechin. Eur. J. Pharmacol; 740: 570-7.

Karim N, Wellendorph P, Absalom N, Johnston GA, Hanrahan JR, Chebib M (2013). Potency of GABA at human recombinant GABA(A) receptors expressed in Xenopus oocytes: a mini review. Amino Acids. 44:1139-49.

Absalom N, Eghorn LF, Villumsen IS, Karim N, Bay T, Olsen JV, Knudsen GM, Bräuner-Osborne H, Frølund B, Clausen RP, Chebib M & Wellendorph P* (2012). Alpha4beta1delta GABAA receptors are high-affinity targets for gamma-hydroxybutyric acid (GHB). Proc Natl Acad Sci USA; 109: 13404-9.

Wellendorph P, Høg S, Sabbatini P, Pedersen MHF, Martiny L, Knudsen GM, Frølund B, Clausen RP & Bräuner-Osborne H (2010). Novel radioiodinated GHB analogues for radiolabeling and photolinking of high-affinity GHB binding sites. J Pharmacol Exp Ther; 335: 456-64.
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