IP3-independent signalling of OX1 orexin/hypocretin receptors to Ca2+ influx and ERK
2007 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 353, no 2, 475-480 p.Article in journal (Refereed) Published
OX1 orexin receptors (OX1R) have been shown to activate receptor-operated Ca2+ influx pathways as their primary signalling pathway; however, investigations are hampered by the fact that orexin receptors also couple to phospholipase C, and therewith inositol-1,4,5-trisphosphate (IP3)-dependent Ca2+ release. We have here devised a method to block the latter signalling in order to focus on the mechanism of Ca2+ influx activation by OX1R in recombinant systems. Transient expression of the IP3-metabolising enzymes IP3-3-kinase-A (inositol-1,4,5-trisphosphate → inositol-1,3,4,5-tetrakisphosphate) and type I IP3-5-phosphatase (inositol-1,4,5-trisphosphate → inositol-1,4-bisphosphate) almost completely attenuated the OX1R-stimulated IP3 elevation and Ca2+ release from intracellular stores. Upon attenuation of the IP3-dependent signalling, the receptor-operated Ca2+ influx pathway became the only source for Ca2+ elevation, enabling mechanistic studies on the receptor-channel coupling. Attenuation of the IP3 elevation did not affect the OX1R-mediated ERK (extracellular signal-regulated kinase) activation in CHO cells, which supports our previous finding of the major importance of receptor-operated Ca2+ influx for this response.
Place, publisher, year, edition, pages
2007. Vol. 353, no 2, 475-480 p.
Orexin, Hypocretin, G-protein-coupled receptor, Receptor-operated Ca2+ channel, Phospholipase C, Phosphoinositide, Extracellular signal-regulated kinase
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-96995DOI: 10.1016/j.bbrc.2006.12.045ISI: 000243543100041PubMedID: 17188243OAI: oai:DiVA.org:uu-96995DiVA: diva2:171754