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Neurokinin 1 receptor isoforms and the control of innate immunity

Joseph Stokes Jr. Research Institute, The Children's Hospital of Philadelphia, USA.
Trends in Immunology (Impact Factor: 12.03). 06/2009; 30(6):271-6. DOI: 10.1016/j.it.2009.03.006
Source: PubMed

ABSTRACT Substance P is the prototype tachykinin peptide and triggers a variety of biological effects in both the nervous and immune system. Two naturally occurring variants of the neurokinin 1 receptor (NK1R) mediate the effects of SP: a 'classic' full-length receptor and a truncated (tail-less) form that lacks 96 amino acid residues at the C-terminus. Most research has focused on the full length receptor and the truncated NK1R has not been extensively explored. Recent data demonstrate that truncated NK1R has important functional roles, including modulation of responses triggered by cytokines, chemotaxis of macrophages and regulation of HIV replication. Targeting the truncated NK1R with pharmacologic agents might result in novel therapeutic approaches in diseases which affect the immune system, including HIV disease.

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    • "Truncated NK1R lacks 96 amino acid residues corresponding to the C-terminus of the full length receptor. Furthermore, activation of full length and truncated NK1R results in differential receptor signalling mediated by different G-proteins [Tuluc et al., 2009] and the truncated form has a 10-fold lower binding affinity to substance P than the long form [Fong et al., 1992]. The long NK1R isoform is prevalent throughout the human brain, while the truncated form is more common in peripheral tissues, but to date there is little evidence for a regionspecific role for the two isoforms in the CNS [Caberlotto et al., 2003]. "
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    • "CRH also induced mRNA expression of only the truncated NK-1 on LAD2 cells which is known to be at least ten times less sensitive than the full length receptor (Tuluc et al., 2009) and was recently shown to be associated with pathological states (Tuluc et al., 2009). These findings could be relevant for the pathogenesis of skin diseases that worsen by stress (Slominski, 2009), (Slominski et al., 2007), such as psoriasis, where both SP (Remröd et al., 2007) and CRH (Tagen et al., 2007), (Slominski et al., 2000) have been implicated. "
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