title: Hemokinin-1 has Substance P-like function in U-251 MG astrocytoma cells: a pharmacological and functional study.
abstract: Substance P (SP) triggers responses in astrocytoma cells, which are considered important for proliferation and neuroimmunomodulatory activity. In this study, we compared the effects of SP with those of the novel tachykinin Hemokinin-1 (HK-1) in the human astrocytoma cell line U-251 MG. We show that U-251 MG cells express high levels of Neurokinin-1 (NK-1) receptors. The binding affinities of 125I-SP and 125I-mHK-1 to these receptors were in a similar, subnanomolar range. HK-1 and SP stimulated Ca2+ mobilization and induced increased cytokine mRNA expression. A specific NK-1 receptor antagonist blocked the observed effects. We conclude that there are no qualitative differences in SP and HK-1-evoked responses, suggesting that both peptides act through NK-1 receptors in U-251 MG cells. Moreover, we show TAC4 mRNA expression in gliomas, indicating a possible involvement of HK-1 in glioma biology.
authors.affiliation: Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, Department of Immunology, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. aberger@uhnres.utoronto.ca
authors.forename: Alexandra
authors.initials: A
authors.lastname: Berger
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Paige
mesh_terms: D000818:Animals; D001254:Astrocytoma; D015152:Blotting, Northern / Q000379:methods; D002118:Calcium / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006593:Hexokinase / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D011498:Protein Precursors / Q000493:pharmacokinetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay / Q000379:methods; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013373:Substance P / Q000493:pharmacokinetics / Q000494:pharmacology*; D015320:Tachykinins / Q000493:pharmacokinetics / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D016207:Cytokines; D007456:Iodine Isotopes; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; C423233:Tac4 protein, mouse; D015320:Tachykinins; D013373:Substance P; C472074:HK1 protein, human; D006593:Hexokinase; D002118:Calcium