Lipid effects on nicotinic acetylcholine receptor gating and kinetics: a structural-functional correlation

The nicotinic acetylcholine receptor (AChR) is still the paradigm of rapid ligand-gated ion channels. Since the early finding of a motionally restricted shell of lipids ( annulus ) in the immediate perimeter of the membrane-bound AChR, experimental evidence has supported the notion that the interface between the protein moiety and the adjacent lipid molecules is the site of action of a variety of pharmacologically relevant substances, including non-competitive inhibitors of the cholinergic system like some local anesthetics, short-chain alcohols, and steroids. Patch-clamp data on cells expressing the AChR protein add another dimension to this knowledge, enabling correlations to be established between the chemical composition of lipid-modified cells and the functional properties (ligand binding, channel gating) of the receptor protein in situ

How do peptides interact with lipid membranes and how does this affect their biological activity?

1. A short review is given of the chemical, physical, and pharmacological development of the idea that target cell lipid membranes may catalyze the interaction between regulatory peptides (or other pharmacologic agents) and their cell surface receptors. 2. The message-address and the membrane compartments concepts explain the observed correlations between the three-dimensional structures of peptides induced by a membrane surface and their preference for a certain receptor subtype. 3. Examples are given for opioid peptides (enkephalin, dynorphin, etc.), tachykinin peptides (substance P, neurokinin A, etc.), and melanocortin peptides (ACTH, alpha-MSH, etc.). 4. Relationships between the conformation of substance P induced by membrane association and that of a non-peptide substance P mimetic are discussed. Possible reasons for the difference between agonistic and antagonistic properties in the peptide field are revealed by this case