TRP channel cannabinoid receptors in skin sensation, homeostasis, and inflammation

Abstract

In the skin, cannabinoid lipids, whether of endogenous or exogenous origin, are capable of regulating numerous sensory, homeostatic, and inflammatory events. Although many of these effects are mediated by metabotropic cannabinoid receptors, a growing body of evidence has revealed that multiple members of the transient receptor potential (TRP) ion channel family can act as "ionotropic cannabinoid receptors". Furthermore, many of these same TRP channels are intimately involved in cutaneous processes that include the initiation of pain, temperature, and itch perception, the maintenance of epidermal homeostasis, the regulation of hair follicles and sebaceous glands, and the modulation of dermatitis. Ionotropic cannabinoid receptors therefore represent potentially attractive targets for the therapeutic use of cannabinoids to treat sensory and dermatological diseases. Furthermore, the interactions between neurons and other cell types that are mediated by cutaneous ionotropic cannabinoid receptors are likely to be recapitulated during physiological and pathophysiological processes in the central nervous system and elsewhere, making the skin an ideal setting in which to dissect general complexities of cannabinoid signaling.

Keywords: Transient receptor potential; cannabinoids; dermatitis; ion channel; nociception; pruritis.

Figure 1

Comparison of metabotropic cannabinoid receptors and TRP channel ionotropic cannabinoid receptors. (A) Metabotropic receptors are seven transmembrane domain-containing proteins that signal via heterotrimeric G proteins. Typical responses resulting from the activation of Gi/Go G proteins by CB1 and CB2 receptors are shown. (B) TRP channel subunits each have six transmembranes domains. Four subunits assemble to form a function channel to mediate influx of sodium and/or calcium ions. ARD, ankyrin repeat domains.

Figure 2

Metabotropic and TRP channel cannabinoid receptor expression across skin cell types. References are listed in the text.