title: The role of Gαs in activation of NK92-MI cells by neuropeptide substance P.
abstract: Substance P (SP) is well known for its immunoregulatory influence on NK cells. The biological actions of SP are mediated primarily through the high-affinity neurokinin-1 receptor (NK-1R), a G protein-coupled receptor (GPCR). Receptor binding triggers a cAMP signaling pathway and intracellular levels of cAMP are regulated via Gαs and Gαi. In this study NF449, a Gαs-selective G protein antagonist, was used to study the role of Gαs in the activation of NK92-MI cells by SP. Results show that 10(-12)M SP enhances the expression of Gαs and Gαi3 in NK92-MI cells promoting a cytotoxic phenotype characterized by expression of perforin and granzyme B. Development of a cytotoxic phenotype in NK92-MI cells stimulated with SP is blunted by inhibition of Gαs by NF449. In summary, SP signaling through NK-1R promotes a cytotoxic phenotype in NK92-MI cells characterized by upregulation of both Gαs and Gαi3. NF449 inhibits Gαs, blunts SP-induced expression of perforin and granzyme B, and represents a potential therapeutic avenue for reducing NK-cell mediated cytotoxicity.
authors.affiliation: Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, China; Liaoning University of Traditional Chinese Medicine, Shenyang, China.
authors.forename: Hou
authors.initials: H
authors.lastname: Diandong
authors.affiliation: Liaoning University of Traditional Chinese Medicine, Shenyang, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Kefeng
authors.affiliation: Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Weixin
authors.affiliation: Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Moran
authors.affiliation: Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Jiahui
authors.affiliation: Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, China. Electronic address: yd_lzf@sina.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zaifu
mesh_terms: D002478:Cells, Cultured; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D054353:Perforin / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*
chemical_list: D054353:Perforin; D013373:Substance P; D053804:Granzymes; D019204:GTP-Binding Proteins; D019205:GTP-Binding Protein alpha Subunits, Gs
keywords: Cytotoxicity; Gi; Gs; Immunoregulation; NK92-MI cells; Substance P