Activation of 5-HT Receptors That Stimulate the Adenylyl Cyclase Pathway Positively Regulates IGF-I in Cultured Craniofacial Mesenchymal CellsLambert H.W. · Weiss E.R. · Lauder J.M.
aDepartment of Cell Biology and Anatomy, University of North Carolina School of Medicine, Chapel Hill, N.C., and bDepartment of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tenn., USA
Results of the present study demonstrate that activation of the adenylyl cyclase/protein kinase A (PKA) pathway leads to increased levels of insulin-like growth factor I (IGF-I) in cultured embryonic mouse mandibular mesenchymal cells. Treatment of serum-free cultures with 10–8M 8-OH-DPAT (DPAT) or with 10–5M forskolin in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX; 10–5M) increased levels of IGF-I (but not IGF-II), as measured by [125I]protein A immunobinding. In a previous study, we showed that DPAT, forskolin, IBMX and the 5-HT4 receptor agonist SC53116 all increased the synthesis of cyclic adenosine monophosphate (cAMP) in these cultures. Taken together, these results provide evidence that stimulation of the adenylyl cyclase/PKA pathway in embryonic mandibular mesenchymal cells positively regulates IGF-I. This is supported by the ability of the PKA inhibitor Rp-cAMPS to block increases in IGF-I caused by both DPAT and forskolin. Consistent with these results, DPAT and forskolin increased phosphorylation of the cAMP response element binding protein (CREB), which was also blocked by Rp-cAMPS. These results suggest that activation of 5-HT receptors positively coupled to the adenylyl cyclase/PKA pathway may promote transcription of IGF-I through a cAMP response element (CRE) in the IGF-I promoter. This may represent one mechanism whereby 5-HT positively regulates IGF-I expression in developing craniofacial mesenchymal cells.
Dr. Jean M. Lauder
Department of Cell Biology and Anatomy
108 Taylor Hall CB No. 7090, University of North Carolina at Chapel Hill
Chapel Hill, NC 27599–7090 (USA)
Tel. +1 919 966 5020, Fax +1 919 966 1856, E-Mail email@example.com
Received: Received: April 9, 2000
Accepted: May 26, 2000
Number of Print Pages : 8
Number of Figures : 4, Number of Tables : 0, Number of References : 56
Vol. 23, No. 1, Year 2001 (Cover Date: January-February 2001)
Journal Editor: A.T. Campagnoni, Los Angeles, Calif.
ISSN: 0378–5866 (print), 1421–9859 (Online)
For additional information: http://www.karger.com/journals/dne