The interaction of insulin and angiotensin II on the regulation of human neuroblastoma cell growth.
This laboratory has previously reported that angiotensin II is a growth factor for human SH-SY5Y neuroblastoma cells, and that a variety of converting enzyme inhibitors and angiotensin II antagonists reduce thymidine incorporation into the DNA of these cells. In the present study, insulin, at 5 micrograms/mL, was found to stimulate thymidine incorporation in SH-SY5Y cells. The insulin effect was only partially inhibited by the converting enzyme inhibitors enalapril, quinapril, and quinaprilat, whereas it was markedly or totally blunted by the angiotensin II antagonists DuP753 and PD123177. In additional studies, IGF-1 (50 ng/mL) significantly stimulated thymidine incorporation into these cells in a fashion indistinguishable from that of insulin. Taken together, these studies are consistent with the suggestion that insulin at high concentrations and IGF at low concentrations enhance the proliferative response of these cells to angiotensin II. The differential effects of converting enzyme inhibition and angiotensin II antagonism on cell proliferation could be explained if converting enzyme inhibition results in low, but effective, levels of angiotensin II in the culture medium, whereas the angiotensin II antagonists effectively block angiotensin II at its receptor. Finally, in this system, both the AT1 receptor blocking agent DuP 753 and the AT2 receptor blocking agent PD123177 appear to be effective.
Chen
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Laboratory of Cellular Biology, Alton Ochsner Medical Foundation, New Orleans, LA 70121.
Prakash
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D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007328:Insulin; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D013936:Thymidine