Poly(ADP-ribose) polymerase-1 is a novel nuclear target for cholinergic receptor signaling in the hippocampus.
Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and transcription regulation. The aim of this study was to investigate the role of PARP-1 in muscarinic cholinergic receptor signaling. Our data indicate that activation of muscarinic cholinergic receptors by carbachol (1mM) in the presence of GTP gamma S evoked a significant enhancement of PARP activity in the adult rat hippocampus. Moreover, TMB-8 (10 microM), an antagonist of inositol 1, 4, 5 trisphosphate (IP(3)) receptor prevented the activation of PARP-1, which indicates that IP(3) /Ca(2+) signaling is involved in this pathway. The diacylglycerol (DAG)-regulated protein kinase C (PKC) inhibitor (GF109203X) (1 microM) only slightly enhanced PARP activity in hippocampal nuclear fractions, which suggests that DAG/ PKC is not involved in PARP activation.
Strosznajder
R P
RP
Department of Respiratory Research, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. roberts@cmdik.pan.pl
Jesko
H
H
Adamczyk
A
A
D000818:Animals; D020013:Calcium Signaling; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D018679:Cholinergic Agonists; D004075:Diglycerides; D007211:Indoles; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D011976:Receptors, Muscarinic; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D002217:Carbachol; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011493:Protein Kinase C; C070515:bisindolylmaleimide I