ABSTRACT
The mammalian brain is enriched in muscarinic cholinergic receptors (mAChR) which constitute a class of related proteins belonging to the family of guanine-nucleotide binding protein-coupled receptors. Five different mAChRs have been cloned and sequenced from the human and rat genome, and Messenger RNAs for all five subtypes have been found in various regions of the brain. This chapter analyses the observations obtained with cells transfected with genes for a type of muscarinic receptor with results obtained in tissues. In tissues, two major signaling pathways for the muscarinic receptor are the stimulation of phosphoinositide hydrolysis and the inhibition of adenylyl cyclase activity. Pure populations of mAChRs will provide the means of obtaining pharmacological profiles of each subtype of receptor. This information is necessary to maximize the possibility of synthesizing compounds that are selective for a given receptor subtype although the high degree of amino acid sequence homology among the subtypes of mAChRs may be an obstacle difficult to overcome.
