Mitogenic effect of serotonin in human small cell lung carcinoma cells via both 5-HT1A and 5-HT1D receptors

We have recently shown that the mitogenic effect of serotonin (5-hydroxytryptamine, 5-HT) on human small cell lung carcinoma (SCLC) cells is at least partly due to stimulation of a 5-HT_1D receptor type. We now report that the 5-HT_1A 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-HT_1D receptor agonist sumatriptan reproduced the maximal [³H]thymidine incorporation observed with 5-HT alone. The 5-HT_1A 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-HT_1A and 5-HT_1D receptor types.