Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antennapedia Homeodomain Protein
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Base Sequence
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Down-Regulation
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Female
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Galanin
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Homeodomain Proteins / chemistry
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Homeodomain Proteins / metabolism
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Humans
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Melanoma / metabolism
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Melanoma / pathology
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Melanoma / physiopathology
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Molecular Sequence Data
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Nuclear Proteins*
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Pain / metabolism
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Pain / physiopathology*
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Peptide Fragments / metabolism
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Peptide Nucleic Acids / chemistry
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Peptide Nucleic Acids / metabolism*
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RNA, Messenger / genetics
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Rats
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Rats, Sprague-Dawley
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Receptor, Galanin, Type 1
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Receptors, Galanin
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Receptors, Neuropeptide / genetics
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Receptors, Neuropeptide / metabolism*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Signal Transduction*
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Spinal Cord / metabolism
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Transcription Factors*
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Tumor Cells, Cultured
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Wasp Venoms
Substances
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Antennapedia Homeodomain Protein
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Homeodomain Proteins
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Nuclear Proteins
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Peptide Fragments
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Peptide Nucleic Acids
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RNA, Messenger
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Receptor, Galanin, Type 1
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Receptors, Galanin
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Receptors, Neuropeptide
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Recombinant Fusion Proteins
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Transcription Factors
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Wasp Venoms
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transportan
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Galanin