Abstract: |
Antisense oligodeoxynucleotides (18-20 bases) to a cloned δ opioid receptor (DOR-1) lower δ binding in NG108-15 cells by 40%-50%. Changing 4 bases to generate a mismatch antisense oligodeoxynucleotide or mixing the corresponding sense and antisense oligodeoxynucleotides prior to treatment of the cells eliminates the inhibition of binding, confirming the specificity of the response. In vivo, an antisense oligodeoxynucleotide to DOR-1 given intrathecally lowers δ, but not μ or κ1 spinal analgesia. The mismatch antisense oligodeoxynucleotide is inactive. δ analgesic sensitivity gradually returns by 5 days after the last antisense treatment, indicating the lack of irreversible damage or toxicity. These studies demonstrate that DOR-1 mediates δ analgesia at the level of the spinal cord and confirm at the molecular level traditional pharmacological studies implying distinct receptor mechanisms for δ, μ, and κ{script}1 analgesia. The use of antisense approaches may prove valuable in understanding the receptors mediating opioid pharmacology. © 1994. |
Keywords: |
nonhuman; binding affinity; animals; mice; cell line; cell specificity; molecular cloning; amino acid sequence; molecular sequence data; nucleotide sequence; cell damage; base sequence; binding sites; receptor affinity; analgesia; receptor binding; opiate receptor; dna, complementary; oligonucleotides, antisense; tritium; adenylate cyclase; deltorphin; receptors, opioid, delta; antisense oligodeoxynucleotide; forskolin; priority journal; article; enkephalins; enkephalin, d-penicillamine (2,5)-; dna base composition
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