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Lidocaine‐induced apoptosis of gingival fibroblasts: participation of cAMP and PKC activity
Author(s) -
Villarruel Emmanuel Quinteros,
Borda Enri,
SterinBorda Leonor,
Orman Betina
Publication year - 2011
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20100200
Subject(s) - staurosporine , protein kinase c , lidocaine , apoptosis , protein kinase a , programmed cell death , pharmacology , mechanism of action , chemistry , stimulation , kinase , microbiology and biotechnology , medicine , biology , endocrinology , anesthesia , biochemistry , in vitro
Local anaesthetics are drugs that prevent or relieve pain by interrupting nervous conduction and are the most commonly used drugs in dentistry. Their main targets of action are voltage‐dependent Na + channels. The Na + channel is modulated by phosphorylation of two enzymes: PKA (protein kinase A) and PKC (protein kinase C). We studied the ability of lidocaine to modulate programmed cell death of human gingival fibroblasts and the mechanisms involved in this process. Lidocaine (10 −5 to 10 −7 M) stimulated apoptosis in primary cultures and the caspase‐3 activity in a concentration‐dependent manner. The stimulatory effect of lidocaine on apoptosis was attenuated in the presence of HA 1004 (PKA inhibitor) and stimulated by staurosporine and Go 6976 (PKC inhibitors). Lidocaine‐induced apoptotic nuclei correlated positively with cAMP accumulation and negatively with PKC activity. These results show that lidocaine promotes apoptosis in human gingival fibroblasts at concentrations used for local anaesthesia. The mechanism involves PKA stimulation and PKC inhibition, which in turn stimulates caspase‐3 and leads to programmed cell death.