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Cholinergic control of epidermal cohesion.

Sergei A Grando¹

¹Department of Dermatology, University of California at Davis, Sacramento, CA 95817, USA. sagrando@ucdavis.edu

Experimental Dermatology

|March 4, 2006

Summary

The human epidermis has a non-neuronal cholinergic system involving keratinocytes and acetylcholine (ACh). This system regulates cell adhesion and is implicated in skin blistering disorders, suggesting potential therapeutic uses for cholinergic drugs.

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Area of Science:

Dermatology
Neuroscience
Molecular Biology

Background:

The human epidermis possesses a non-neuronal cholinergic system.
This system comprises the keratinocyte (KC) acetylcholine (ACh) axis, including enzymes for ACh synthesis and degradation.
Two classes of ACh receptors, nicotinic and muscarinic, mediate ACh's biological effects in the skin.

Purpose of the Study:

To investigate the role of the keratinocyte ACh axis in regulating cell adhesion.
To identify downstream targets and signaling pathways affected by ACh.
To explore the involvement of the KC ACh axis in various cutaneous blistering conditions.

Main Methods:

Analysis of the keratinocyte (KC) acetylcholine (ACh) axis components.
Investigation of ACh receptor subtypes and their downstream effects on cell adhesion molecules.
Examination of signaling pathways, including kinase cascades, affecting cell adhesion molecule expression and phosphorylation.
Correlation of KC ACh axis components with blistering disorders.

Main Results:

Cutaneous ACh regulates keratinocyte cell-cell and cell-matrix adhesion.
ACh acts via nicotinic and muscarinic receptors on intercellular adhesion molecules (cadherins, integrins).
Signaling pathways involving kinase cascades modulate cell adhesion molecule expression and phosphorylation.
KC ACh axis components are implicated in pemphigus, epidermolysis bullosa, thermal burns, and vesication.

Conclusions:

The keratinocyte ACh axis is crucial for regulating epidermal adhesion.
Dysregulation of this axis contributes to skin blistering diseases.
Cholinergic drugs show promise for treating pemphigus and potentially other blistering disorders.

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