Multiple phospholipase activation by OX(1) orexin/hypocretin receptors
2008 (English)In: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 65, no 12, 1948-1956 p.Article in journal (Refereed) Published
We investigated coupling of OX(1) receptors to phospholipase activation and diacylglycerol generation in Chinese hamster ovary (CHO) cells using both biochemical and fluorescence "real-time" methods. The results indicate that at lowest orexin-A concentrations (highest potency), diacylglycerol generated results from phospholipase D activity. At 10-100-fold higher orexin-A concentrations, phospholipase C is activated, likely hydrolyzing phosphatidylinositol (PI) or phosphatidylinositol monophosphate (PIP) but not phosphatidylinositol bisphosphate (PIP(2)). At further 7-fold higher orexin-A concentrations, PIP(2) is hydrolyzed, releasing both diacylglycerol and inositol-1,4,5-trisphosphate. Thus, OX(1) orexin receptors connect to multiple phospholipase activities, apparently composed of at least one phospholipase D and two different phospholipase C activities. At low agonist concentrations, diacylglycerol and phosphatidic acid are the preferred products, and interestingly, it seems that even the primarily activated phospholipase C mainly works to increase diacylglycerol and not inositol-1,4,5-trisphosphate.
Place, publisher, year, edition, pages
2008. Vol. 65, no 12, 1948-1956 p.
Orexin, hypocretin, phospholipase C, phospholipase D, phosphoinositides, phosphatidylcholine, diacylglycerol, live cell imaging
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-111131DOI: 10.1007/s00018-008-8206-zISI: 000256927400017PubMedID: 18488139OAI: oai:DiVA.org:uu-111131DiVA: diva2:279465