Inhibition of trifluoperazine-induced DNA fragmentation by cyclic AMP mediated signaling.
Trifluoperazine (TFP), a phenothiazine antipsychotic agent with calmodulin antagonist property, induces DNA fragmentation in a dose- and time-dependent manner in PC12 cells. Various agents affecting calcium mediated intracellular signal transduction such as calcium chelators, calcium ionopores, inhibitors of phospholipase C, and activators/inhibitors of protein kinase C did not block TFP-induced DNA fragmentation. Some of these agents themselves induced DNA fragmentation in the conditions under which they were examined. However, cholera toxin (selective Gs activator), forskolin (adenylate cyclase activator) or dibutyryl cyclic AMP (cyclic AMP analogue) inhibited TFP-induced DNA fragmentation in a dose-dependent manner. These results suggest that it is not the calcium but the Gs and adenylate cyclase pathways that play an important role in TFP-induced DNA fragmentation in PC12 cells.
Kang
U G
UG
Department of Psychiatry, Seoul National University College of Medicine, Korea.
Kim
M J
MJ
Suh
P G
PG
Ryu
S H
SH
Park
J B
JB
Kim
J H
JH
Kim
Y S
YS
Lee
Y H
YH
D037361:Adenylate Cyclase Toxin; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction; D014268:Trifluoperazine / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D014268:Trifluoperazine; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D001973:Bromodeoxyuridine