Hemokinin-1 has Substance P-like function in U-251 MG astrocytoma cells: a pharmacological and functional study

J Neuroimmunol. 2005 Jul;164(1-2):48-56. doi: 10.1016/j.jneuroim.2005.03.016.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytoma
  • Blotting, Northern / methods
  • Calcium / metabolism
  • Cell Count / methods
  • Cell Line, Tumor
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Hexokinase / pharmacokinetics
  • Hexokinase / pharmacology*
  • Humans
  • Immunohistochemistry / methods
  • Iodine Isotopes / pharmacokinetics
  • Mice
  • Protein Binding / drug effects
  • Protein Precursors / pharmacokinetics
  • Protein Precursors / pharmacology*
  • RNA, Messenger / biosynthesis
  • Radioligand Assay / methods
  • Receptors, Neurokinin-1 / genetics
  • Receptors, Neurokinin-1 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Substance P / pharmacokinetics
  • Substance P / pharmacology*
  • Tachykinins / pharmacokinetics
  • Tachykinins / pharmacology*
  • Time Factors

Substances

  • Cytokines
  • Iodine Isotopes
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Neurokinin-1
  • Tac4 protein, mouse
  • Tachykinins
  • Substance P
  • HK1 protein, human
  • Hexokinase
  • Calcium