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MELATONIN-INDUCED SUPPRESSION OF PC12 CELL GROWTH IS MEDIATED BY ITS GI COUPLED TRANSMEMBRANE RECEPTORS. (R826248)
Roth, J. A., T. Rosenblatt, A. Lis, AND R. Bucelli. MELATONIN-INDUCED SUPPRESSION OF PC12 CELL GROWTH IS MEDIATED BY ITS GI COUPLED TRANSMEMBRANE RECEPTORS. (R826248). GEOPHYSICAL RESEARCH LETTERS. American Chemical Society, Washington, DC, 919:139-146, (2001).
The effects of pertussis toxin, an uncoupler of Gi protein from adenylate cyclase, and luzindole, a competitive inhibitor of melatonin receptor binding, were examined for their ability to inhibit melatonin-induced suppression of PC12 cell growth. Both agents inhibited the melatonin response suggesting that melatonin may be acting through one of its Gi coupled cell surface receptors. This is confirmed by Western blots demonstrating the presence of MT1 receptors in PC12 cells. Coupling of the Gi protein to these receptors is demonstrated by failure of melatonin to suppress cell growth in PKA deficient A126-1B2-1 mutant PC12 cells. Similarly, melatonin failed to prevent cell proliferation when cells were incubated in the presence of the PKA inhibitor, Rp-cAMP. Retinoic acid and dexamethasone, agents known to effect PC12 cell growth and/or differentiation, displayed differential effects on the actions of melatonin. In the presence of melatonin and low concentrations of retinoic acid (100 nM), PC12 cell proliferation was stimulated compared to that seen with either agent alone, whereas no increase in cell proliferation was observed when higher concentrations of retinoic acid (100 M) were used. The effects of dexamethasone on suppression of PC12 cell growth were additive with that of melatonin whereas, 1,25-dihydroxyvitamin D3 (IC50=10 nM), which by itself had no effect on PC12 cell growth, was found to inhibit the melatonin response. This study demonstrates that inhibition of PC12 cell growth, at physiological concentrations of melatonin, is mediated by cAMP-dependent cell surface receptors and this response is altered by other growth factors known to effect PC12 cell proliferation and differentiation.
Author Keywords: Melatonin; PC12 cells; Vitamin D; Dexamethasone; Retinoic acid; Cell proliferation
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL CENTER FOR ENVIRONMENTAL RESEARCH