REGULATION OF THE EXPRESSION AND FUNCTION OF THE M-2 MUSCARINIC RECEPTOR

Since the cloning and expression of many of the G protein-coupled rece ptors during the 1980s, there has been a massive increase in our under standing of many aspects of their function. The use of molecular biolo gy to engineer and express mutant receptors has made it possible to de termine key amino acids involved in receptor function. Although advanc es in molecular biology have contributed greatly to our understanding of the pharmacology and structure of the five subtypes of muscarinic r eceptor, much remains to be learned about the factors that regulate th eir expression and function. This review by El-Bdaoui Haddad and Jonat han Rousell describes the current state of awareness and highlights re cent advances made in the elucidation of the mechanisms involved in mu scarinic receptor regulation. Because most is known about the regulati on of expression of the M-2 receptor subtype, particular attention wil l be paid to it. Furthermore, this receptor subtype plays an important role in regulating acetylcholine output from airway cholinergic nerve s, and there is substantial evidence from studies both in vivo and in vitro in human and animal models that these receptors are dysfunctiona l in asthma.