Role of protein kinase C and cAMP in fluoxetine effects on human T-cell proliferation.
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 after stimulation with mitogens. We found that fluoxetine promoted the Ca2+ -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+ mobilization.
Edgar
V A
VA
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Sterin-Borda
L
L
Cremaschi
G A
GA
Genaro
A M
AM
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
D018687:Antidepressive Agents, Second-Generation; D007476:Ionophores; D005473:Fluoxetine; D003208:Concanavalin A; D000001:Calcimycin; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium