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Serotonin and serotoninergic agents affect proliferation of normal and transformed lymphoid cells
1Rugjer Bosković Institute, Department of Experimental Biology and Medicine, Zagreb, Croatia.
Abstract:
Blastogenic transformation of murine spleen cells elicited with concanavalin A was suppressed by serotonin 10(-12) to 10(-6) M, and marginally stimulated by its antagonists ketanserin and propranolol in low concentrations (10(-15) to 10(-11) M). Ketanserin (5-HT2 receptor ligand) and propranolol (5-HT1A and beta-adrenergic ligand) did not block the suppressive effect of serotonin if used along with it in equimolar concentrations (10(-9) M). Ergot-alkaloid dihydroergosine suppressed, whereas dihydroergotoxin stimulated the blastogenic transformation. Opposite effects of the agents were obtained in experiments with mouse myeloma X63/Ag 8.653 and hybridoma SHV 125 cell lines, which unlike normal lymphoid cells, are homologous cell populations and proliferate spontaneously. The data indicate that serotonin and its antagonists interfere directly with mitosis and/or autocrine stimulation of target cells.
Insights
Serotonin suppresses immune cell activation, while its antagonists show minimal effects. These compounds appear to directly impact cell division and growth signaling in both normal and cancerous cells.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Serotonin's role in immune responses is complex and not fully understood.
- Investigating serotonin's influence on lymphocyte proliferation is crucial for understanding immune regulation.
- Specific serotonin receptor ligands offer tools to probe these interactions.
Purpose of the Study:
- To investigate the effects of serotonin and its antagonists on concanavalin A-induced murine spleen cell blastogenesis.
- To explore the direct impact of these compounds on spontaneously proliferating myeloma and hybridoma cell lines.
- To elucidate the mechanisms by which serotonin and its antagonists modulate cell proliferation.
Main Methods:
- Murine spleen cells were stimulated with concanavalin A and treated with varying concentrations of serotonin, ketanserin, and propranolol.
- The blastogenic transformation of spleen cells was measured.
- Experiments were also conducted on mouse myeloma (X63/Ag 8.653) and hybridoma (SHV 125) cell lines.
Main Results:
- Serotonin significantly suppressed concanavalin A-induced blastogenic transformation of spleen cells.
- Serotonin antagonists ketanserin and propranolol showed marginal stimulation at very low concentrations but did not block serotonin's suppressive effect.
- Dihydroergosine suppressed, while dihydroergotoxin stimulated, blastogenesis; opposite effects were observed in myeloma and hybridoma cell lines.
Conclusions:
- Serotonin directly interferes with the mitosis and/or autocrine stimulation of lymphoid cells.
- The differential effects on normal lymphocytes versus cancer cell lines suggest distinct cellular mechanisms.
- Further research is needed to fully understand serotonin's complex role in immune cell regulation and cancer proliferation.