Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo.
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.
Pooga
M
M
Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories, Stockholm University, Sweden.
Soomets
U
U
Hällbrink
M
M
Valkna
A
A
Saar
K
K
Rezaei
K
K
Kahl
U
U
Hao
J X
JX
Xu
X J
XJ
Wiesenfeld-Hallin
Z
Z
Hökfelt
T
T
Bartfai
T
T
Langel
U
U
D000595:Amino Acid Sequence; D000818:Animals; D051943:Antennapedia Homeodomain Protein; D001483:Base Sequence; D015536:Down-Regulation; D005260:Female; D019004:Galanin; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D010446:Peptide Fragments / Q000378:metabolism; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044091:Receptor, Galanin, Type 1; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D014862:Wasp Venoms
D051943:Antennapedia Homeodomain Protein; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D020135:Peptide Nucleic Acids; D012333:RNA, Messenger; D044091:Receptor, Galanin, Type 1; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014862:Wasp Venoms; C110068:transportan; D019004:Galanin