Received for publication July 27, 2006.
Revised August 24, 2006.
Accepted for publication September 11, 2006.

Role of the agonist binding site in upregulation of neuronal nicotinic 42 receptors

Abstract

Chronic exposure to nicotinic ligands results in upregulation of neuronal nicotinic 42 receptors in the brain and in heterologous expression systems. Upregulation can be produced by a variety of drugs, including nicotinic agonists and competitive antagonists, but previous studies have indicated that the signal for upregulation does not reflect a traditional nicotinic pharmacology and the initial steps in signal transduction are not clear. We examined the signal for upregulation, and the possible involvement of the nicotine binding site in signal reception, using mutated subunits transiently expressed in HEK293 cells. The data indicate that receptor activation and desensitization are not part of the signaling pathway. However, mutations to residues in the binding site can affect upregulation. These results provide evidence that the binding site is directly involved in receiving the signal for upregulation.

Key words: Nicotinic cholinergic, Ion channel regulation, Mutagenesis/Chimeric approaches

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