Serotonin receptor agonists that increase cyclic AMP positively regulate IGF-I in mouse mandibular mesenchymal cells.
Evidence from the present study suggests that activation of both 5-HT(1A) and 5-HT(4) (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-HT(1A) or 5-HT(4) 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-HT(1A) or 5-HT(4) 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-HT(1A) or 5-HT(4) receptors may be one mechanism by which serotonin regulates IGF-I synthesis in developing craniofacial mesenchymal cells.
Lambert
H W
HW
Department of Cell Biology and Anatomy, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7090, USA.
Lauder
J M
JM
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism*; D003545:Cysteine / Q000494:pharmacology; D004622:Embryo, Mammalian; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000096:biosynthesis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008334:Mandible / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009526:Nialamide / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D062366:para-Aminobenzoates
D001549:Benzamides; D003470:Culture Media; D016895:Culture Media, Serum-Free; D010879:Piperazines; D011758:Pyrroles; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D062366:para-Aminobenzoates; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C072790:2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester; C074211:SC 53116; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D000242:Cyclic AMP; D003545:Cysteine; D009526:Nialamide; D010129:4-Aminobenzoic Acid