Koschatzky S, Tschammer N, Gmeiner P (2011)
Publication Language: English
Publication Type: Journal article, Original article
Publication year: 2011
Original Authors: Koschatzky S., Tschammer N., Gmeiner P.
Publisher: American Chemical Society
Book Volume: 2
Pages Range: 308-316
Journal Issue: 6
DOI: 10.1021/cn200020y
Dopaminergic systems have been described to functionally interact with the neuromodulatory peptide neurotensin. Employing fluorescence detected coimmunoprecipitation and radioligand binding experiments, we herein demonstrate that coexpression of dopamine D receptor and the neurotensin receptor subtype NTS leads to physical interaction and the formation of heteromers in transfected human embryonic kidney 293 cells. In this in vitro system, a trans-inhibitory effect on the agonist binding affinity of D was observed in presence of neurotensin. To correlate between the functional properties of dopaminergic agents and the magnitude of neurotensin-induced modulation of D binding affinities in cells coexpressing D and NTS, a structurally diverse set of dopamine receptor agonists, partial agonists, and antagonists was tested. Ligand specific profiles indicating substantial bias between ligand efficacy and transmodulation were discovered, suggesting a heteromerization-based functional selectivity. In the presence of neurotensin, the novel D agonist FAUC 326 displayed a 34-fold decrease of binding affinity in cells coexpressing D and NTS. © 2011 American Chemical Society.
APA:
Koschatzky, S., Tschammer, N., & Gmeiner, P. (2011). Cross-receptor interactions between dopamine D2L and neurotensin NTS1 receptors modulate binding affinities of dopaminergics. ACS Chemical Neuroscience, 2(6), 308-316. https://doi.org/10.1021/cn200020y
MLA:
Koschatzky, Susanne, Nuska Tschammer, and Peter Gmeiner. "Cross-receptor interactions between dopamine D2L and neurotensin NTS1 receptors modulate binding affinities of dopaminergics." ACS Chemical Neuroscience 2.6 (2011): 308-316.
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