Toxins from mamba venoms: small proteins with selectivities for different subtypes of muscarinic acetylcholine receptors

Abstract

Muscarinic acetylcholine receptors exist as five subtypes that are widely distributed throughout the body. Conventional pharmacological agents are not highly selective for particular subtypes, making investigations on the functional significance of the subtypes difficult. Recent findings indicate that mamba snake venoms contain several small proteins ('muscarinic toxins') that are highly specific for muscarinic receptors, and are discussed in this review by Diana Jerusalinsky and Alan Harvey. Some of these toxins act selectively and irreversibly on individual subtypes of receptor, and some are antagonists, while others activate muscarinic receptors. The toxins should be useful tools in studies of the functions of individual receptor subtypes, and comparisons of their three-dimensional structures should give clues about how selective binding to muscarinic receptor subtypes can be obtained.