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Nicotinic acetylcholine receptor α[sub 7] regulates cAMP signal within lipid rafts.
- Source :
-
American Journal of Physiology: Cell Physiology . Sep2003, Vol. 285 Issue 3, pC567-C574. 8p. 20 Black and White Photographs, 7 Graphs. - Publication Year :
- 2003
-
Abstract
- Neuronal nicotinic acetylcholine receptors (nAChRs) are made of multiple subunits with diversified functions. The nAChR α[sub 7]-subunit has a property of high Ca[sup 2+] permeability and may have specific functions and localization within the plasma membrane as a signal transduction molecule. In PC-12 cells, fractionation by sucrose gradient centrifugation revealed that nAChRα[sub 7] existed in low-density, cholesterol-enriched plasma membrane microdomains known as lipid rafts where fiotillin also exists. In contrast, nAChR α[sub 5]- and β[sub 2]-subunits were located in high-density fractions, out of the lipid rafts. Type 6 adenylyl cyclase (AC6), a calcium-inhibitable isoform, was also found in lipid rafts and was coimmunoprecipitated with nAChRα[sub 7]. Cholesterol depletion from plasma membranes with methylβ-cyclodextrin redistributed nAChRα[sub 7] and AC6 diffusely within plasma membranes. Nicotine stimulation reduced forskolin-stimulated AC activity by 35%, and this inhibition was negated by either treatment with α-bungarotoxin, a specific antagonist of nAChRα[sub 7], or cholesterol depletion from plasma membranes. The effect of cholesterol depletion was negated by the addition of cholesterol. These data suggest that nAChRα[sub 7] has a specific membrane localization relative to other nAChR subunits and that lipid rafts are necessary to localize nAChRα[sub 7] with AC within plasma membranes. In addition, nAChRα[sub 7] may regulate the AC activity via Ca[sup 2+] within lipid rafts. [ABSTRACT FROM AUTHOR]
- Subjects :
- *NICOTINIC receptors
*CYCLIC adenylic acid
*LIPIDS
Subjects
Details
- Language :
- English
- ISSN :
- 03636143
- Volume :
- 285
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Cell Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 10775632
- Full Text :
- https://doi.org/10.1152/ajpcell.00422.2002