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Orexin/hypocretin receptor chimaeras reveal structural features important for orexin peptide distinction
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology. (Kukkonen)
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2011 (English)In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 585, no 9, 1368-1374 p.Article in journal (Refereed) Published
Abstract [en]

We wanted to analyze the basis for the distinction between OX(1) and OX(2) orexin receptors by the known agonists, orexin-A, orexin-B and Ala(11), d-Leu(15)-orexin-B, of which the latter two show some selectivity for OX(2). For this, chimaeric OX(1)/OX(2) and OX(2)/OX(1) orexin receptors were generated. The receptors were transiently expressed in HEK-293 cells, and potencies of the agonists to elicit cytosolic Ca(2+) elevation were measured. The results show that the N-terminal regions of the receptor are most important, and the exchange of the area from the C-terminal part of the transmembrane helix 2 to the transmembrane helix 4 is enough to lead to an almost total change of the receptor's ligand profile.

Place, publisher, year, edition, pages
2011. Vol. 585, no 9, 1368-1374 p.
Keyword [en]
Orexin, Hypocretin, Calcium, Orexin-A, Orexin-B
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-152736DOI: 10.1016/j.febslet.2011.04.020ISI: 000290248300019PubMedID: 21510948OAI: oai:DiVA.org:uu-152736DiVA: diva2:413892
Available from: 2011-04-29 Created: 2011-04-29 Last updated: 2011-05-26Bibliographically approved

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