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Chapter 9: Advances and limitations of the molecular neuroanatomy of cholinergic receptors: the example of multiple muscarinic receptors

Elsevier Science & Technology
DOI: 10.1016/s0079-6123(08)62385-7
  • Biology
  • Mathematics
  • Pharmacology


Publisher Summary The past few years have witnessed a considerable progress in the understanding of many facets of neurotransmitter receptor function. Many of these advances have been facilitated by the molecular cloning of the genes or cDNAs encoding several dozens of neurotransmitter receptors. Thus, much information is now available on their primary structures, on their putative trans-membrane topology, on the domains involved in ligand binding or second messenger coupling, on their distribution in the brain and on the mechanisms of receptor regulation. A rather unexpected fact uncovered by the molecular cloning studies is the existence for practically any known neurotransmitter of a number of receptor subtypes higher than that previously postulated on pharmacological grounds. A similar situation is observed for the neurotransmitter acetylcholine and its family of muscarinic receptors. Initial pharmacological classifications divided muscarinic receptors into M1 and M2 subtypes, on the basis of, respectively, their high and low affinity for the antagonist pirenzepine. This chapter summarizes recent work on the localization of muscarinic receptor transcripts in the rat brain, on their co-distribution with cholinergic cells and on the establishment of conditions to achieve preferential labeling of each receptor subtype with some of the presently available muscarinic radioligands.

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