Re-sensitization of neuropeptide receptors: should we stop the recycling?

Neurogenic inflammation, an important component of many disease states, is mediated by the release of neuropeptides from sensory nerves. To date, it has been possible to inhibit neurogenic inflammation using neuropeptide receptor blockers or by prevention of neuropeptide release. In the current edition of the British Journal of Pharmacology, Cattaruzza and co-workers discuss a novel way of blocking the action of neuropeptides. They have shown that the re-sensitization of the substance P neurokinin-1 receptor and the substance P-induced pro-inflammatory effects are mediated by the enzyme, endothelin-converting enzyme 1 (ECE-1). Therein, they showed that ECE-1 inhibition could prevent the re-sensitization process. This is exciting progress in our understanding of neurogenic inflammation, but it remains to be seen how inhibition of receptor recycling via ECE-1 blockade will affect other inflammatory pathways.