Modulation of substance P/neurokinin-1 receptor in human astrocytoma cells by antisense oligodeoxynucleotides.
1. An antisense oligodeoxynucleotide corresponding to the NH2-terminus of the substance P (SP)/neurokinin-1 (SP/NK1) receptor was constructed and added to cultures of human astrocytoma U-87 MG cells in vitro and rats in vivo. 2. Antisense oligodeoxynucleotide at a concentration of 30 microM progressively reduced the specific binding [3H][Sar9, Met(O2)11]-SP, selective SP/NK1 receptor agonist, in the U-87 MG astrocytoma cells by approx. 31% on the second day after treatment (control: 26.1 +/- 2.4 fmol/mg protein vs antisense oligodeoxynucleotide: 18.0 +/- 1.4 fmol/mg protein, P < 0.001). 3. Treatment with 30 microM antisense oligodeoxynucleotide for 2 days inhibited the SP/MK1 receptor-induced influx of 45Ca2+ into the U-87 MG cells by approx. 35%. 4. When the same antisense oligodeoxynucleotides were encapsulated in liposomes and injected into the lateral cerebral ventricle of rats, functional SP receptor was blocked.
Ogo
H
H
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
Hirai
Y
Y
Miki
S
S
Nishio
H
H
Akiyama
M
M
Nakata
Y
Y
D000818:Animals; D001254:Astrocytoma / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007276:Injections, Intraventricular; D008081:Liposomes; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008081:Liposomes; D064729:Neurokinin-1 Receptor Antagonists; D016376:Oligonucleotides, Antisense; D018040:Receptors, Neurokinin-1; D002118:Calcium