A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor-mediated apoptosis in glioblastomas.

Journal Article (Journal Article)

Previous studies have shown that neurokinin 1 receptor (NK1R) occurs naturally in human glioblastomas and its stimulation causes cell proliferation. In the present study we show that stimulation of NK1R in human U373 glioblastoma cells by substance P increases Akt phosphorylation by 2.5-fold, with an EC(50) of 57 nM. Blockade of NK1R lowers basal phosphorylation of Akt, indicating the presence of a constitutively active form of NK1R; similar results are seen in U251 MG and DBTRG-05 glioblastoma cells. Linkage of NK1R to Akt implicates NK1R in apoptosis of glioblastoma cells. Indeed, treatment of serum-starved U373 cells with substance P reduces apoptosis by 53 +/- 1% (p < 0.05), and treatment with NK1R antagonist L-733,060 increases apoptosis by 64 +/- 16% (p < 0.01). Further, the blockade of NK1R in human glioblastoma cells with L-733,060 causes cleavage of Caspase-3 and proteolysis of poly (ADP-ribose) polymerase. Experiments designed to elucidate the mechanism of NK1R-mediated Akt phosphorylation revealed total involvement of non-receptor tyrosine kinase Src and phosphatidyl-3-kinase, a partial involvement of epidermal growth factor receptor, and no involvement of mitogen-activated protein/extracellular signal-related kinase. Taken together, the results of the present study indicate a key role for NK1R in glioblastoma apoptosis.

Full Text

Duke Authors

Cited Authors

  • Akazawa, T; Kwatra, SG; Goldsmith, LE; Richardson, MD; Cox, EA; Sampson, JH; Kwatra, MM

Published Date

  • May 2009

Published In

Volume / Issue

  • 109 / 4

Start / End Page

  • 1079 - 1086

PubMed ID

  • 19519779

Pubmed Central ID

  • PMC2696067

Electronic International Standard Serial Number (EISSN)

  • 1471-4159

Digital Object Identifier (DOI)

  • 10.1111/j.1471-4159.2009.06032.x


  • eng

Conference Location

  • England