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Effect of the tricyclic antidepressant desipramine on protein kinase C in rat brain and rabbit platelets in vitro
Author(s) -
MORISHITA SHIGERU,
WATANABE SYOSUKE
Publication year - 1997
Publication title -
psychiatry and clinical neurosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 74
eISSN - 1440-1819
pISSN - 1323-1316
DOI - 10.1111/j.1440-1819.1997.tb02592.x
Subject(s) - desipramine , protein kinase c , tricyclic antidepressant , serotonin , platelet , neurotransmitter , pharmacology , endocrinology , chemistry , tricyclic , medicine , antidepressant , inhibitory postsynaptic potential , in vitro , biology , kinase , biochemistry , hippocampus , central nervous system , receptor
Protein kinase C (PKC), which participates in cellular responses to various stimuli such as hormones, neurotransmitters and growth factors, is essential for cell proliferation and differentiation. Desipramine, which is a tricyclic antidepressant, inhibited PKC activity in concentrations starting from 0.1 mmol/L in rat brain and its inhibitory effect on PKC activity did not involve competitive inhibition with calcium. However, rabbit platelets incubated with desipramine showed a biphasic dose—response change in PKC activity in vitro . The stimulatory effect of desipramine on PKC activity in rabbit platelets was observed over a concentration range of 0.5–2.0 mmol/L, and an inhibitory effect on PKC activity in platelets began to be seen at a concentration of 3.0 mmol/L desipramine. The stimulatory effects of desipramine and calcium on PKC activity in platelets appear to be occurring by the same mechanism. Several lines of evidence indicate that neurotransmitter uptake is linked to PKC activation. The present study supposes that the inhibitory effect of desipramine on neurotransmitter uptake may, at least in part, be associated with its inhibitory or stimulatory effect on PKC.