Muscarinic receptor agonists and antagonists: effects on inflammation and immunity.

School of Public Health, Harvard University, 665 Huntington Avenue, Boston, MA 02115, USA.
Handbook of experimental pharmacology 01/2012; DOI: 10.1007/978-3-642-23274-9_17
Source: PubMed

ABSTRACT In this chapter, we will review what is known about muscarinic regulation of immune cells and the contribution of immune cell muscarinic receptors to inflammatory disease and immunity. In particular, immune cell expression of cholinergic machinery, muscarinic receptor subtypes and functional consequences of agonist stimulation will be reviewed. Lastly, this chapter will discuss the potential therapeutic effects of selective antagonists on immune cell function and inflammatory disease in recent animal studies and human clinical trials.

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    ABSTRACT: Acetylcholine has been implicated in both the pathophysiology and treatment of a number of psychiatric disorders, with most of the data related to its role and therapeutic potential focusing on schizophrenia. However, there is little thought given to the consequences of the documented changes in the cholinergic system and how they may affect the functioning of the brain. This review looks at the cholinergic system and its interactions with the intrinsic neurotransmitters glutamate and gamma-amino butyric acid as well as those with the projection neurotransmitters most implicated in the pathophysiologies of psychiatric disorders; dopamine and serotonin. In addition, with the recent focus on the role of factors normally associated with inflammation in the pathophysiologies of psychiatric disorders, links between the cholinergic system and these factors will also be examined. These interfaces are put into context, primarily for schizophrenia, by looking at the changes in each of these systems in the disorder and exploring, theoretically, whether the changes are interconnected with those seen in the cholinergic system. Thus, this review will provide a comprehensive overview of the connectivity between the cholinergic system and some of the major areas of research into the pathophysiologies of psychiatric disorders, resulting in a critical appraisal of the potential outcomes of a dysregulated central cholinergic system.
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