Functional characterization of neurokinin-1 receptors on human U373MG astrocytoma cells.
The neurokinin-1 (NK-1, substance P) receptor belongs to the class of seven transmembrane domain (7-TM) receptors that interact with cellular effector systems via guanine nucleotide binding regulatory proteins (G-proteins). In this study, coupling mechanisms of functional NK-1 receptors endogenously expressed in a human astrocytoma cell line (U373MG) were analyzed. Stimulation with substance P (SP) resulted in 1) a rapid increase in inositol 1,4,5-trisphosphate (IP3) synthesis; 2) a rise in cytosolic free calcium concentration ([Ca2+]i); 3) induction of immediate early gene transcription as monitored by c-fos and c-jun expression; and 4) a significant increase in de novo DNA synthesis. Thus, the functional responses induced by stimulation of NK-1 receptors on U373MG strongly correlate with those observed after treatment of primary astrocytes with SP and make U373MG cells a useful in vitro model system for the analysis of NK-1 receptor function on astrocytes in vivo.
Eistetter
H R
HR
Department of Cell Biology, Glaxo Institute for Molecular Biology S.A., Plan-les-Ouates, Switzerland.
Mills
A
A
Brewster
R
R
Alouani
S
S
Rambosson
C
C
Kawashima
E
E
D001254:Astrocytoma / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D006868:Hydrolysis; D007293:Inosine Triphosphate / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000378:metabolism; D011869:Radioligand Assay; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D010716:Phosphatidylinositols; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D007293:Inosine Triphosphate; D004247:DNA; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium