Insulin and IGF-I stimulated RNA synthesis in primary cultures of neuronal cells: involvement of cyclic AMP and protein kinase-C.

ABSTRACT

Insulin and insulin-like growth factor I promote the growth of rat neuronal cells in primary culture. In order to investigate the mechanism of hormone signalling in this biological system, we studied the effect of cyclic AMP agonists and a protein kinase C stimulator on basal and hormone-induced RNA synthesis. Agents elevating endogenous cyclic AMP levels (forskolin, dibutyryl cyclic AMP, cholera toxin) blocked the stimulatory effects of both insulin and the growth factor; dibutyryl cyclic AMP, however, altered the binding of neither hormone. Although, unlike the aforementioned agents, phorbol ester significantly elevated basal RNA synthesis; it nevertheless inhibited the stimulation by insulin; this latter effect probably being mediated by an increase in intracellular cyclic AMP levels, as has been found in other cell types. Staurosporine, an inhibitor of protein kinase C, also blocked the effects of insulin on RNA synthesis.