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Repeated amphetamine treatment induces neurite outgrowth and enhanced amphetamine‐stimulated dopamine release in rat pheochromocytoma cells (PC12 cells) via a protein kinase C‐ and mitogen activated protein kinase‐dependent mechanism
Author(s) -
Park Yang Hae,
Kantor Lana,
Guptaroy Bipasha,
Zhang Minjia,
Wang Kevin K. W.,
Gnegy Margaret E.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02127.x
Subject(s) - neurite , protein kinase c , protein kinase a , chelerythrine , amphetamine , activator (genetics) , chemistry , microbiology and biotechnology , cyclin dependent kinase 5 , mitogen activated protein kinase , mitogen activated protein kinase kinase , kinase , dopamine , biology , biochemistry , endocrinology , in vitro , receptor
Repeated intermittent treatment with amphetamine (AMPH) induces both neurite outgrowth and enhanced AMPH‐stimulated dopamine (DA) release in PC12 cells. We investigated the role of protein kinases in the induction of these AMPH‐mediated events by using inhibitors of protein kinase C (PKC), mitogen activated protein kinase (MAP kinase) or protein kinase A (PKA). PKC inhibitors chelerythrine (100 n m and 300 n m ), Ro31‐8220 (300 n m ) and the MAP kinase kinase inhibitor, PD98059 (30 µ m ) inhibited the ability of AMPH to elicit both neurite outgrowth and the enhanced AMPH‐stimulated DA release. The direct‐acting PKC activator, 12‐ O ‐tetradecanoyl phorbol 13‐acetate (TPA, 250 n m ) mimicked the ability of AMPH to elicit neurite outgrowth and enhanced DA release. On the contrary, a selective PKA inhibitor, 100 µ m Rp‐8‐Br‐cAMPS, blocked only the development of AMPH‐stimulated DA release but not the neurite outgrowth. Treatment of the cells with acute AMPH elicited an increase in the activity of PKC and MAP kinase but not PKA. These results demonstrated that AMPH‐induced increases in MAP kinase and PKC are important for induction of both the enhancement in transporter‐mediated DA release and neurite outgrowth but PKA was only required for the enhancement in AMPH‐stimulated DA release. Therefore the mechanisms by which AMPH induces neurite outgrowth and the enhancement in AMPH‐stimulated DA release can be differentiated.