Role of protein kinase C and cAMP in fluoxetine effects on human T-cell proliferation

VALERIA AYELLI-EDGAR; LEONOR STERIN BORDA; GRACIELA ALICIA CREMASCHI; ANA MARÍA GENARO

EUROPEAN JOURNAL OF PHARMACOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 1999 vol. 372 p. 65 - 73

0014-2999

In this work, we studied the effect of fluoxetine on human T-lymphocyte proliferation using optimal and suboptimal concanavalin A concentrations. In particular, we analyzed the influence of fluoxetine on the kinases that are involved in intracellular signalling afterstimulation with mitogens. We found that fluoxetine promoted the Ca2q-mediated proteolysis of protein kinase C PKC. and increased cyclic-AMP cAMP. levels, thereby impairing lymphocyte proliferation, when optimal concanavalin A concentrations were used. In contrast, when suboptimal concanavalin A concentrations were used, fluoxetine only increased PKC translocation, without modifying cAMP levels, leading to T-cell proliferation. According to our results, fluoxetine has a dual effect on T-cell proliferation by modulating the PKC and protein kinase A pathways. This mechanism is thought to be mediated through Ca2+