Substance P activates responses correlated with tumour growth in human glioma cell lines bearing tachykinin NK1 receptors.
The neuropeptide substance P (SP), by stimulating tachykinin NK1 receptors (NK1R), triggers a number of biological responses in human glioma cells which are potentially relevant for tumour growth. First, radioligand binding studies demonstrated the presence of tachykinin NK1R on SNB-19, DBTRG-05 MG and U373 MG, but not on U138 MG and MOG-G-GCM human glioma cell lines. Second, application of SP or neurokinin A (NKA) to NK1R+ glioma cell lines increased the secretion of interleukin 6 (IL-6) and potentiated IL-6 secretion induced by IL-1beta. SP also up-regulated the release of transforming growth factor beta1 (TGF-beta1) by the U373 MG glioma cell line. Third, SP induced new DNA synthesis and enhanced the proliferation rate of NK1R+, but not of NK1R- glioma cell lines. Also, NKA stimulated the proliferation and cytokine secretion in NK1R+ glioma cell lines. All the stimulant effects of SP/NKA on NK1R+ glioma cell lines were completely blocked by a specific tachykinin NK1R antagonist, MEN 11467. These data support the potential use of tachykinin NK1R antagonist for controlling the proliferative rate of human gliomas.
Palma
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C
Menarini Ricerche, Department of Pharmacology, Pomezia, RM, Italy.
Nardelli
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Manzini
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Maggi
C A
CA
D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000378:metabolism; D015288:Neurokinin A / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1 / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D015850:Interleukin-6; D009363:Neoplasm Proteins; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D013373:Substance P; D015288:Neurokinin A