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The new study shows that in this process skin cells produce nitric oxide, a versatile signaling molecule involved in temperature-sensing and wound-healing. This alternative, oxygen-independent mode of nitric oxide production previously had been thought to occur only outside cells.
"This alternative nitric oxide production process could prove to be crucial in the clinic," said Professor Ardem Patapoutian at the Dorris Neuroscience Center at Scripps Research and the senior author of the study. "The usual nitric oxide production process requires oxygen, so drugs that target that process might not work when oxygen availability is low after blood supply disruption."
Patapoutian's lab focuses on the molecular biology of skin-based sensory pathways—pathways that typically start with stimulus-sensing receptors on nerve ends. Such receptors include the TRPV (transient receptor potential vanilloid) class of receptors, which are sensitive to various temperature- and pain-related stimuli. One of these receptors, TRPV3, is found not only on some nerve cells and nerve ends, but also on outer skin cells known as keratinocytes.
Patapoutian, his graduate student Takashi Miyamoto, and their colleagues demonstrated that TRPV3 activation leads to the production of nitric oxide in keratinocytes—which suggests that nitric oxide is the carrier of thermosensory signals from skin cells to nearby nerve ends. A simple gas consisting of one atom of nitrogen bound to one atom of oxygen, nitric oxide is one of the more evolutionarily ancient biological signaling molecules, and even plays a role as a neurotransmitter in the brain.
"Nitric oxide was high on our list of possibilities because it is known to be produced in keratinocytes when they are warmed," said Miyamoto, who was first author of the study.
Nitric oxide's versatility as a signaling molecule also led the researchers to look for other processes in which the TRPV3-mediated pathway might be involved. "We found evidence that the nitric oxide produced by this pathway makes a partial contribution to wound-healing and also specifically to the keratinocyte migration that occurs during wound healing," said Miyamoto.
"The dogma has been that nitric oxide can be produced in cells only with NOS enzymes, but this study hints that nitrite-based nitric oxide production could potentially be just as important," Miyamoto said.
MEDICA.de; Source: Scripps Research Institute