BETA-ADRENERGIC-RECEPTOR ACTIVATION PROMOTES PROCESS OUTGROWTH IN AN EMBRYONIC RAT BASAL FOREBRAIN CELL-LINE AND IN PRIMARY NEURONS

A clonal cell line, AS583-8.E4.22, from the embryonic day 15 rat basal forebrain was established using retrovirus-mediated transduction of a temperature-sensitive mutant of the simian virus 40 (SV40) large tumo ur antigen. The cell line expresses cytoskeletal and neurotransmitter features indicative of neuronal commitment, In response to agents that increase intracellular cAMP, including forskolin and catecholamines, the cell line exhibits rapid process outgrowth and growth cone formati on that does not require new gene expression or protein synthesis. The neurite outgrowth induced by catecholamines is mediated by beta 2-adr energic receptors and is characterized by a rapid, reversible redistri bution of filamentous actin. Neurons from primary cultures of embryoni c day 15 basal forebrain were also found to respond to beta-adrenergic receptor agonists by enhancing growth cone formation. These results s uggest that catecholamines provide cues that induce cytoskeletal rearr angements leading to neuronal process outgrowth and growth cone format ion in the developing basal forebrain and possibly other neuronal prog enitor cell populations. The neuronal basal forebrain cell line provid es an ideal model to study the signalling mechanisms underlying the ca techolamine-induced process outgrowth.