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.