Subtypes of Muscarinic Cholinergic Receptors

Abstract

Acetylcholine released from neurons has effects on many biological processes. These effects are mediated through two major classes of receptors termed nicotinic and muscarinic cholinergic receptors. There is currently strong evidence supporting the concept that both of these major classes of cholinergic receptors are themselves comprised of distinct subtypes of receptors. For example, the nicotinic receptors on autonomic ganglia have very different properties from those on skeletal muscle, suggesting that there are at least two subtypes of the nicotinic cholinergic receptor (Taylor, 1985). The genes encoding the subunits of nicotinic receptors have been isolated and sequenced from both muscle and nerve, and indeed these molecules have distinct primary structures (Boulter et al., 1985, 1986). Similarly, the existence of subtypes of mAChR has long been postulated on the basis of distinct pharmacologic profiles of some muscarinic receptors, and recently, several genes have been isolated and sequenced that appear to code for distinct subtypes of muscarinic receptors (Kubo et al., 1986a,b; Peralta et al., 1987a,b; Bonner et al., 1987, 1988; Braun et al., 1987; Akiba et al., 1988). Thus, it appears that there are at least five distinct genes that code for proteins that have the properties of muscarinic receptors in both the human and rat genome (Bonner et al., 1987, 1988). This chapter will attempt to put into historical perspective the various reports that have led us to our current thinking with regard to subtypes of muscarinic receptors.