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Acetylcholine receptors in cutaneous biology – receptorology and therapeutic implications
Author(s) -
Grando S.
Publication year - 2004
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.0906-6705.2004.0212an.x
Subject(s) - muscarinic acetylcholine receptor , nicotinic agonist , acetylcholine receptor , cholinergic , microbiology and biotechnology , receptor , biology , acetylcholine , muscarinic acetylcholine receptor m4 , neuroscience , pharmacology , biochemistry
Free cytotransmitter acetylcholine (ACh) is present in physiologically relevant concentrations in human skin, and ACh and cholinergic drugs alter vital functions of keratinocytes (KCs). KCs respond to ACh via classical ACh receptor types that use Ca 2+ as a second messenger. The repertoire of cholinergic receptors changes with cell maturation, so that at each stage of their development, KCs respond to ACh via different combinations of nicotinic (nAChR) and muscarinic (mAChR) receptors. Basal KCs respond to ACh predominantly via α3β2(β4) ± α5 nAChRs and the M3 mAChR; prickle KCs have more α5‐containing α3 nAChRs and also express α9 nAChR as well as M4 and M5 mAChRs; granular KCs posses mainly α7 nAChR and M1 mAChR. We used three independent approaches to elucidate role of each receptor in KC biology: 1) Subtype selective drugs, 2) Gene silencing with small interfering RNA or antisense oligonucleotides, and 3) Gene knockout in transgenic mice. Obtained results indicate that KC nAChRs and mAChR exhibit synergistic control of cell adhesion and crawling locomotion. KC cell‐cell adhesion is regulated through α3 and α9 nAChRs as well as M3 mAChR. KC chemokinesis is controlled by α3 and α7 nAChRs and M3 and M4 mAChRs. KC chemotaxis toward nicotinic agonists is mediated by α7 nAChR. These findings offer novel insights into the mechanisms of ACh‐mediated modulation of epidermalization and may aid the development of novel methods to promote wound healing and inhibit tumor metastasis.