Multiple phospholipase activation by OX(1) orexin/hypocretin receptors.

Full Abstract

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.

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Author information

Author/s: Johansson, L (L); Ekholm, M E (ME); Kukkonen, J P (JP);

Affiliation: Department of Neuroscience, Unit of Physiology, Uppsala University, Uppsala, Sweden.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci), published in Switzerland. (Language: eng)

Reference: 2008-Jun; vol 65 (issue 12) : pp 1948-56

Dates: Created 2008/06/19; Completed 2008/08/13;

PMID: 18488139, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
CHO Cells
Cricetinae
Cricetulus
Diglycerides - metabolism
Enzyme Activation
Humans

Intracellular Signaling Peptides and Proteins - pharmacology
Neuropeptides - pharmacology
Phosphatidylinositol 4,5-Diphosphate - metabolism
Phospholipase D - metabolism
Receptors, G-Protein-Coupled - metabolism
Receptors, Neuropeptide - metabolism
Type C Phospholipases - metabolism

Associated Chemicals: Diglycerides (0) ; Intracellular Signaling Peptides and Proteins (0) ; Neuropeptides (0) ; Phosphatidylinositol 4,5-Diphosphate (0) ; Receptors, G-Protein-Coupled (0) ; Receptors, Neuropeptide (0) ; orexin receptors (0) ; orexins (0) ; Type C Phospholipases (EC 3.1.4.-) ; Phospholipase D (EC 3.1.4.4)

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