Intrathecal administration of PNA targeting galanin receptor reduces galanin-mediated inhibitory effect in the rat spinal cord.
Peptide nucleic acids (PNA) are nucleic acid analogues containing neutral amide backbone, forming stable and tight complexes with complementary DNA/RNA. However, it is unclear whether unmodified PNA can efficiently penetrate neuronal tissue in order to act as antisense reagent. Here we show that intrathecal (i.t.) injection of an unmodified antisense PNA complementary to the rat galanin receptor type 1 (GalR1) mRNA is able to block the inhibitory effect of i.t. administered galanin on spinal nociceptive transmission. Autoradiographic ligand binding studies using [125I]galanin show that the unmodified PNA is able to reduce the density of galanin binding sites in the dorsal horn. Thus, unmodified PNA applied i.t. appears to function as an effective antisense reagent in rat spinal cord in vivo.
Rezaei
K
K
Department of Neurochemistry and Neurotoxicology, Stockholm University, Sweden.
Xu
I S
IS
Wu
W P
WP
Shi
T J
TJ
Soomets
U
U
Land
T
T
Xu
X J
XJ
Wiesenfeld-Hallin
Z
Z
Hökfelt
T
T
Bartfai
T
T
Langel
U
U
D000818:Animals; D001345:Autoradiography; D016503:Drug Delivery Systems; D004594:Electrophysiology; D005260:Female; D019004:Galanin / Q000494:pharmacology*; D007278:Injections, Spinal; D007457:Iodine Radioisotopes; D008024:Ligands; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020135:Peptide Nucleic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044091:Receptor, Galanin, Type 1; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000235:genetics* / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D007457:Iodine Radioisotopes; D008024:Ligands; D016376:Oligonucleotides, Antisense; D020135:Peptide Nucleic Acids; D044091:Receptor, Galanin, Type 1; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D019004:Galanin