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- Title
Desensitization of Human Muscarinic Acetylcholine Receptor m2 Subtypes Is Caused by Their Sequestration/Internalization1.
- Authors
Tsuga, Hirofumi; Kameyama, Kimihiko; Haga, Tatsuya
- Abstract
Desensitization of human muscarinic acetylcholine receptor m2 subtypes (hm2 receptors) stably expressed in chinese hamster ovary cells was measured as decreases in the carbamylcholine-stimulated [35S]GTPγS binding activity in membrane preparations after pretreatment of cells with carbamylcholine. The extent of carbamylcholine-stimulated [35S]-GTPγS binding activity was found to decrease to 64% following pretreatment of cells with 10 μM carbamylcholine for 30 min, and under the same conditions 51–59% of hm2 receptors were sequestered/internalized as assessed by decreases in the [3H] N-methylscopolamine binding activity on the cell surface. A similar reduction in the carbamylcholine-stimulated [35S]GTPγS binding activity was observed by pretreatment of cells with 5 nM propylbenzylylcholine mustard, which irreversibly bound to and inactivated 58% of the hm2 receptors. When the cells were pretreated with 10 μM carbamylcholine in the presence of 0.32 M sucrose, which is known to inhibit clathrin-mediated endocytosis, no sequestration/ internalization of hm2 receptors was observed, and the extent of carbamylcholine-stimulated [35S]GTPγS binding activity did not change. These results indicate that desensitization of hm2 receptors may be caused by reduction of receptor number on the cell surface through sequestration/internalization rather than by loss of the function of receptors.
- Subjects
DESENSITIZATION (Psychotherapy); MUSCARINIC acetylcholine receptors; CARBON sequestration; PSYCHOANALYSIS; NEUROTRANSMITTERS
- Publication
Journal of Biochemistry, 1998, Vol 124, Issue 4, p863
- ISSN
0021-924X
- Publication type
Article
- DOI
10.1093/oxfordjournals.jbchem.a022191