Evidence from the present study suggests that activation of both 5-HT1A and 5-HT4 (5-hydroxytryptamine) receptor subtypes stimulates cyclic adenosine monophosphate (cAMP) synthesis in cultured embryonic mouse mandibular mesenchymal cells (micromass cultures). When these cells were grown in serum-free medium and treated with 10–8 M agonist selective for either the 5-HT1A or 5-HT4 receptor subtype (8-OH-DPAT and SC53116, respectively), this significantly stimulated cAMP synthesis and increased insulin-like growth factor I (IGF-I), but not IGF-II, protein levels compared to vehicle-treated controls, as measured by semi-quantitative immunobinding assays. Consistent with these results, IGF-I was significantly decreased when mandibular mesenchymal cells were grown in serum-containing medium (which contains micromolar amounts of 5-HT from fetal calf serum) and treated with 10–8 M antagonist selective for the 5-HT1A or 5-HT4 receptor subtype (NAN-190 on SDZ-205,557). Forskolin also stimulated cAMP and IGF-I (but not IGF-II) in both serum-containing and serum-free cultures. These results indicate that activation of 5-HT receptors that increase cAMP promotes synthesis of IGF-I. This may occur by activation of the cAMP response element sequence present in the IGF-I promoter region. Stimulation of the adenylyl cyclase pathway by activation of 5-HT1A or 5-HT4 receptors may be one mechanism by which serotonin regulates IGF-I synthesis in developing craniofacial mesenchymal cells.

Keywords:
Insulin-like growth factors, 5-HT, IGF-II, Adenylyl cyclase, Craniofacial cartilage proteoglycan core protein, Embryonic, Development, cAMP, Chondrogenesis, 5-HT1A
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1999
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