Community Research and Development Information Service - CORDIS

The skin's molecular players

Apart from being a barrier to the external environment, the skin constitutes the biggest sensory organ. Understanding the mechanism underlying these functions will impact the pharmacological design of skin analgesics.
The skin's molecular players
The skin collects important information and enables sensation of mechanical, chemical and thermal stimuli as well as pain or itching. This is achieved through dense sensory innervation of the skin, which receives and transmits external stimuli.

Various molecules regulate this process, including ion channels of the transient receptor potential family (TRP channels), which exhibit high sensitivity to various physical stimuli and to diverse chemical ligands. Apart from playing a role in sensation of temperature, pain and itching, TRP channels represent appealing drug targets, especially in pain-associated syndromes.

The primary objective of the EU-funded TRPM3 IN SKIN (Cellular regulation of transient receptor potential melastatin 3 (TRPM3) and its role in skin sensation) project was to investigate TRPM3, a less-known member of the melastatin subfamily of TRP channels. Scientists worked to understand how TRPM3 is regulated at the molecular and cellular levels and how this influences the role of this channel in the sensory functions of the skin.

Using a plethora of research methods, the consortium discovered that the membrane lipids phosphoinositols were necessary for the function of TRPM3. External stimuli activating phospholipase C via other receptors inhibited TRPM3 function through degradation of phosphoinositols, a phenomenon that could be reversed by ATP.

An important project achievement was the description of a novel mechanism of function of TRPM3 through the opening of an alternative ion permeation pore. Animal experiments indicated that this activation mechanism could short-circuit TRPM3 and aggravate the onset of pain. Furthermore, researchers discovered that the immunosuppressant rapamycin activated another thermosensitive TRP channel, the cold sensitive TRPM8, opening up new avenues for pharmacological intervention.

Taken together, the study's findings have provided fundamental insight into the role and mechanism of action of ion channels in the skin. Apart from helping to comprehend how these molecules participate in pathological conditions associated with altered sensation, the results could lead to the design of TRPM3-targeting drugs as potential analgesics.

Related information


Skin, analgesics, pain, itching, TRP channels, drug targets, TRPM3, rapamycin
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