Muscarinic receptor agonists and antagonists: effects on keratinocyte functions.
The stratified epithelium enveloping the skin and lining the surfaces of oral and vaginal mucosa is comprised by keratinocytes that synthesize, secrete, degrade, and respond to acetylcholine via muscarinic and nicotinic receptors. The two pathways may compete or synergize with one another, so that net biologic effect represents the biologic sum of the effects of distinct acetylcholine receptors expressed by a keratinocyte at a particular stage of its development. Keratinocytes express a unique combination of muscarinic receptor subtypes at each stage of their development. Experimental results indicate that muscarinic receptors expressed in human keratinocytes regulate their viability, proliferation, migration, adhesion, and terminal differentiation, hair follicle cycling, and secretion of humectants, cytokines, and growth factors. Learning the muscarinic pharmacology of keratinocyte development and functions has salient clinical implications for patients with nonhealing wounds, mucocutaneous cancers, and various autoimmune and inflammatory diseases. Successful therapy of pemphigus lesions with topical pilocarpine and disappearance of psoriatic lesions due to systemic atropine therapy illustrate that such therapeutic approach is feasible.
Departments of Dermatology and Biological Chemistry, University of California, 134 Sprague Hall, Irvine, CA 92697, USA. sgrando@uci.edu
Sergei A
SA
Grando
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012871:Skin Diseases / Q000188:drug therapy / Q000378:metabolism
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000109:Acetylcholine