Back to Search
Start Over
Modulation of D1-like dopamine receptor function by aldehydic products of lipid peroxidation.
- Source :
-
Brain research [Brain Res] 2003 Apr 04; Vol. 968 (1), pp. 102-13. - Publication Year :
- 2003
-
Abstract
- Growing evidence indicates that aldehydic products of lipid peroxidation play an important role in the pathophysiology of neurodegenerative disorders such as Parkinson's disease. In the present study, modulation of D1-like receptor binding and function by saturated alkanals and unsaturated alkenals, 4-hydroxynonenal (4-HNE) and trans-2-nonenal (nonenal), was examined in rat striatal membranes. The 4-HNE and nonenal were most effective in modulating both the specific D1-like receptor binding and function as measured by adenylate cyclase activation. Inactivation of receptor binding and the depression of adenylate cyclase activity were partially prevented by protection of the D1/D5-receptor with the agonist (R)-SKF 38393 or the specific antagonist SCH 23390. 4-HNE inhibited adenylate cyclase activation by Gpp (NH)p and forskolin, indicating the modulation of Gsalpha and the catalytic subunit of adenylate cyclase, respectively. Our data suggests that aldehydic products of lipid peroxidation can directly modulate the binding and functional properties of D1/D5 receptors, as well as effector proteins within their signaling pathway.
- Subjects :
- 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine pharmacokinetics
Adenylyl Cyclases metabolism
Animals
Benzazepines pharmacokinetics
Cell Line
Cell Membrane metabolism
Colforsin pharmacology
Corpus Striatum metabolism
Cyclic AMP metabolism
Cysteine Proteinase Inhibitors pharmacology
Dopamine pharmacology
Dopamine Antagonists pharmacokinetics
Dose-Response Relationship, Drug
Guanylyl Imidodiphosphate pharmacology
Humans
Hydrogen Peroxide pharmacology
Male
Radioligand Assay methods
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D1 drug effects
Receptors, Dopamine D5
Aldehydes pharmacology
Benzazepines analogs & derivatives
Corpus Striatum drug effects
Lipid Peroxidation physiology
Receptors, Dopamine D1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-8993
- Volume :
- 968
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 12644268
- Full Text :
- https://doi.org/10.1016/s0006-8993(02)04279-8