Desensitization and Down Regulation of Muscarinic Acetylcholine Receptors
Abstract
The regulation of muscarinic acetylcholine receptors by short-term exposure to agonists was investigated in intact mouse neuroblastoma (clone N1E- 115) cells, using the hydrophilic ligand (tritium)N-methylscopolamine. It was found that preincubation of cells with 1 mM carbamylcholine for 30 min at 37 C, followed by extensive washing, led to a significant reduction in the subsequent specific binding of 0.2 nM (tritium)N-methylscopolamine. Regulation of muscarinic acetylcholine receptor sensitivity and density was examined upon pre- exposure to muscarinic receptor agonists. Pretreatment of neuronal cells in culture resulted in a significant decrease in the response in phosphoinositude hydrolysis. This treatment also resulted in a decrease in the concentration of cell surface muscarinic receptors. This decrease in receptors ligands. However, it resulted in a selective decrease in the relative densities of M sub 1 muscarinic receptors which have a high affinity for the selective antagonist pirenzepine. Activation of protein kinase C by phorbol esters also resulted in decreasing the responsiveness of muscarinic receptors. However, there was no change in receptor density. Keywords: Muscarinic antagonists, Atropine, Scopolamine, Quinuclidinyl benzilate(QNB).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 22, 1988
- Accession Number
- ADA197570
Entities
People
- Esam E. El-fakahany
Organizations
- University of Maryland, Baltimore