Mitogenic effect of serotonin in human small cell lung carcinoma cells via both 5-HT1A and 5-HT1D receptors
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M G Cattaneo1, R Fesce, L M Vicentini
1Department of Medical Pharmacology, University of Milan, Italy.
Abstract:
We have recently shown that the mitogenic effect of serotonin (5-hydroxytryptamine, 5-HT) on human small lung carcinoma (SCLC) cells is at least partly due to stimulation of a 5-HT1D receptor type. We now report that the 5-HT1A receptor agonist R(+)-8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT) is also capable of stimulating [3H]thymidine incorporation into SCLC GLC-8 cells, although with lower efficacy than 5-HT. The simultaneous administration of maximal doses of 8-OH-DPAT and the 5-HT1D receptor agonist sumatriptan reproduced the maximal [3H]thymidine incorporation observed with 5-HT alone. The 5-HT1A receptor antagonists spiperone and SDZ 216-525 completely abolished the effect of 8-OH-DPAT (IC50 30 nM for both drugs) behaving as pure antagonists. Accordingly, the two drugs partially inhibited the mitogenic effect of 5-HT. These data indicate that the mitogenic effect of 5-HT in SCLC cells involves both 5-HT1A and 5-HT1D receptor types.
Insights
Serotonin (5-hydroxytryptamine, 5-HT) stimulates small lung carcinoma (SCLC) cell growth through both 5-HT1A and 5-HT1D receptors. This study identifies these serotonin receptor types as key players in SCLC proliferation.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Serotonin (5-hydroxytryptamine, 5-HT) has a known mitogenic effect on human small lung carcinoma (SCLC) cells.
- Previous research indicated that this effect is partly mediated by the 5-HT1D receptor type.
Purpose of the Study:
- To investigate the role of the 5-HT1A receptor in the mitogenic effects of serotonin on SCLC cells.
- To determine if 5-HT1A and 5-HT1D receptors are both involved in serotonin-induced SCLC cell proliferation.
Main Methods:
- Utilized the 5-HT1A receptor agonist R(+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to assess its effect on [3H]thymidine incorporation in SCLC GLC-8 cells.
- Administered 8-OH-DPAT and the 5-HT1D agonist sumatriptan simultaneously to evaluate combined effects.
- Employed 5-HT1A receptor antagonists (spiperone and SDZ 216-525) to block 8-OH-DPAT's effects and assess their impact on 5-HT-induced mitogenesis.
Main Results:
- The 5-HT1A agonist 8-OH-DPAT stimulated [3H]thymidine incorporation in SCLC cells, albeit with lower efficacy than 5-HT.
- Combined maximal doses of 8-OH-DPAT and sumatriptan replicated the maximal mitogenic effect of 5-HT alone.
- Spiperone and SDZ 216-525 acted as pure 5-HT1A antagonists, completely blocking 8-OH-DPAT's effect and partially inhibiting 5-HT's mitogenic action.
Conclusions:
- The mitogenic effect of serotonin on SCLC cells involves the activation of both 5-HT1A and 5-HT1D receptor types.
- These findings highlight the dual receptor involvement of serotonin in SCLC cell proliferation.
- Targeting both 5-HT1A and 5-HT1D receptors may offer novel therapeutic strategies for SCLC.