Authors
Agnes Leffler, Ingela Ahlstedt, Susanna Engberg, Arne Svensson, Martin Billger, Lisa Öberg, Magnus K Bjursell, Erik Lindström, Bengt von Mentzer
Publication date
2009/5/1
Journal
Biochemical pharmacology
Volume
77
Issue
9
Pages
1522-1530
Publisher
Elsevier
Description
Tachykinin NK receptors (NKRs) differ to a large degree among species with respect to their affinities for small molecule antagonists. The aims of the present study were to clone NKRs from gerbil (NK2R and NK3R) and dog (NK1R, NK2R and NK3R) in which the sequence was previously unknown and to investigate the potency of several NKR antagonists at all known human, dog, gerbil and rat NKRs. The NKR protein coding sequences were cloned and expressed in CHO cells. The inhibitory concentrations of selective and non-selective NKR antagonists were determined by inhibition of agonist-induced mobilization of intracellular Ca2+. Receptor homology models were constructed based on the rhodopsin crystal structure to investigate and identify the antagonist binding sites and interaction points in the transmembrane (TM) regions of the NKRs. Data collected using the cloned dog NK1R confirmed that the dog …
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