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/hTK(1)) receptor was constru cted and added to cultures of human astrocytoma U-87 MG cells in vitro and rats in vivo. 2. Antisense oligodeoxynucleotide al a concentratio n of 30 mu M progressively reduced the specific binding [H-3][Sar(9), Met(O-2)(11)]-SP, selective SP/NK1 receptor agonist, in the U-87 MG as trocytoma cells by approx. 31% on the second day after treatment (cont rol: 26.1 +/- 2.4 fmol/mg protein vs antisense oligodeoxynucleotide: 1 8.0 +/- 1.4 fmol/mg protein, P < 0.001). 3. Treatment with 30 mu M ant isense oligodeoxynucleotide for 2 days inhibited the SP/MK(1) receptor -induced influx of Ca-45(2+) into the U-87 MG cells by approx. 35%. 4. When the same antisense oligodeoxynucleotides were encapsulated in li posomes and injected into the lateral cerebral ventricle of rats, func tional SP receptor was blocked.