Sensory-nerve-derived neuropeptides: possible therapeutic targets.

This review examines our developing understanding of the families and activities of some of the best known sensory-nerve-derived inflammatory neuropeptides, namely substance P, calcitonin gene-related peptide and galanin. Evidence to date shows involvement of these transmitters in a wide range of systems that includes roles as inflammatory modulators. There is an increasing understanding of the mechanisms involved in the release of the peptides from sensory nerves and these are key in understanding the potential of neuropeptides in modulating inflammatory responses and may also provide novel targets for anti-inflammatory therapy.

Evidence that the modulatory effect of galanin on inflammatory edema formation is mediated by the galanin receptor 3 in the murine microvasculature.

Neuropeptides released from cutaneous nerves are attracting interest as modulators of inflammation in the skin. Recently, we showed that the neuropeptides galanin and galanin-like peptide potently inhibit inflammatory edema by reduction of microvascular blood flow. Reverse transcription-polymerase chain reaction analysis of murine skin revealed the expression of galanin receptors 2 and 3.

Targeted disruption of the galanin gene attenuates inflammatory responses in murine skin.

The release of neuropeptides from primary sensory nerve fibers has been implicated in the modulation of local immune responses in surface tissues, such as the skin and the gastrointestinal mucosa, thereby inducing neurogenic inflammation, which is characterized by plasma extravasation and vasodilatation. In addition, cytokines, either alone or in conjunction with neuropeptides, initiate recruitment of immunocompetent cells such as neutrophils during the initial phases of inflammation. Growing evidence suggests that the neuropeptide galanin plays an important role in skin immune defense and pathophysiology.

Alarin is a vasoactive peptide.

Galanin-like peptide (GALP) is a hypothalamic neuropeptide belonging to the galanin family of peptides. The GALP gene is characterized by extensive differential splicing in a variety of murine tissues. One splice variant excludes exon 3 and results in a frame shift leading to a novel peptide sequence and a stop codon after 49 aa.

Galanin-like peptides exert potent vasoactive functions in vivo.

The cutaneous vasculature plays a key role in the pathophysiology of inflammatory skin diseases. The vascular activity is under the control of the peripheral nervous system that includes locally released neuropeptides. Recently, we detected receptors for the neuropeptide galanin in association with dermal blood vessels, suggesting a role of the galanin-peptide-family in the regulation of the cutaneous microvasculature.