Joan Heller

Research on muscarinic receptors is advancing at an extraordinary rate. Ten years ago, the existence of muscarinic receptor sub- types was a logical assumption with only scattered experimen- tal support. The discovery that pirenzepine recognized apparent heterogeneity in muscarinic binding sites infused new life into the problem of subclassifying muscarinic receptors. Simultaneous advances in molecular biology created a frenzy to clone cell sur- face receptors. The muscarinic receptor succumbed surprisingly quickly, revealing its structure and that of at least four closely related gene products within a year. Our hope of obtaining clear evidence for muscarinic receptor subtypes was answered with a vengeance. Now a family of muscarinic receptors sits before us, asking to be understood. The bounty is as attractive to those who have not previously studied muscarinic receptors as to those who have dedicated their research careers to this subject. The goal of this book is to ensure that the new generation of research will profit from the wisdom of the past. The tools of molecular biology are well suited to the tasks of characteriz- ing the pharmacology, function, and regulation of the distinct muscarinic receptor subtypes. However, efficient and intelligent use of these tools is not possible, unless one understands the properties of the receptor, the molecular mechanisms by which it couples to effectors, and the ways that it is regulated.