Mol. Cells 1999; 9(6): 596~602  
Inhibition of Trifluoperazine-induced DNA Fragmentation by Cyclic AMP Mediated Signaling
Ung Gu Kang Myung Jong Kim, Pann-Ghill Suh, Sung Ho Ryu, Joo-Bae Park, Jung-Hye Kim, Yong Sik Kim, and Young Han Lee*
; Published online December 31, 1999.
© The Korean Society for Molecular and Cellular Biology. All rights reserved.

ABSTRACT
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.

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