uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Orexin signaling in recombinant neuron-like cells
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Physiology.
2002 In: FEBS Letters, ISSN 00145793, Vol. 526, no 1-3, 11-14 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2002. Vol. 526, no 1-3, 11-14 p.
Identifiers
URN: urn:nbn:se:uu:diva-92171OAI: oai:DiVA.org:uu-92171DiVA: diva2:165152
Available from: 2004-11-25 Created: 2004-11-25Bibliographically approved
In thesis
1. Signaling via Orexin Receptors: A Pharmacological Study
Open this publication in new window or tab >>Signaling via Orexin Receptors: A Pharmacological Study
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The orexin receptors are a pair of newly discovered G-protein coupled receptors which are activated by the neuropeptides orexins and play a role in sleep/vigilance, apetite/metabolism and neuroendocrine regulation. On a cellular level receptor activation results in, to name but a few effects, elevation of intracellular calcium and depolarisation. All cellular effects display an uncommon dependence of extracellular Ca2+, which has been shown to be due to influx of extracellular Ca2+ as a primary response.

Here we provide evidence for a high specificity of orexin receptors for orexin peptides over other neuropeptides, despite previous reports of the opposite. Other neuropeptides could neither displace orexin-A from orexin receptors, nor affect functional responses induced by orexin peptides via orexin receptors. In an effort to assess the determinants of orexin-A binding to orexin receptors orexin-A was truncated/mutated and tested for functional responses. It was found that alterations in the orexin-A sequence had more prominent effects on the activation of OX1 than on OX2 receptors.

When the signaling of orexin receptors was investigated in neuron-like cells it was found that they couple to Ca2+-metabolism and PLC activation in a manner similar to that in non-neuronal cells. Investigations of OX1 receptor regulation of adenylyl cyclases showed orexin receptors to have a dual effect on the production of cAMP. A high-affinity inhibitory coupling and a low-affinity stimulatory coupling. The stimulatory coupling was determined to consist of two components, a low potency GS-coupling and a high-potency PKC coupling.

In conclusion we have shown that orexin receptors are preferentially activated by orexin peptides and the receptors couple to Ca2+-metabolism in a similar way in different contexts. Orexin receptors couple to both the phospholipase C and the adenylyl cyclase pathway and to some extent these pathways converge in the production of cAMP.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 40 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1376
Keyword
Physiology, orexin, receptors, calcium, cAMP, adenylyl cyclases, Fysiologi
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-4570 (URN)91-554-6049-6 (ISBN)
Public defence
2004-12-18, B21, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2004-11-25 Created: 2004-11-25 Last updated: 2013-09-20Bibliographically approved

Open Access in DiVA

No full text

By organisation
Physiology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 330 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf