transportan and Pain

Peptide nucleic acids (PNAs) form stable and tight complexes with complementary DNA and/or RNA and would be promising antisense reagents if their cellular delivery could be improved. We show that a 21-mer PNA, complementary to the human galanin receptor type 1 mRNA, coupled to the cellular transporter peptides, transportan or pAntennapedia(43-58), is efficiently taken up into Bowes cells where they block the expression of galanin receptors. In rat, the intrathecal administration of the peptide-PNA construct results in a decrease in galanin binding in the dorsal horn. The decrease in binding results in the inability of galanin to inhibit the C fibers stimulation-induced facilitation of the rat flexor reflex, demonstrating that peptide-PNA constructs act in vivo to suppress expression of functional galanin receptors.

Topics: Amino Acid Sequence; Animals; Antennapedia Homeodomain Protein; Base Sequence; Down-Regulation; Female; Galanin; Homeodomain Proteins; Humans; Melanoma; Molecular Sequence Data; Nuclear Proteins; Pain; Peptide Fragments; Peptide Nucleic Acids; Rats; Rats, Sprague-Dawley; Receptor, Galanin, Type 1; Receptors, Galanin; Receptors, Neuropeptide; Recombinant Fusion Proteins; RNA, Messenger; Signal Transduction; Spinal Cord; Transcription Factors; Tumor Cells, Cultured; Wasp Venoms