ENHANCED NEURONAL DIFFERENTIATION OF NTERA-2 CELLS EXPRESSING NEURONALLY RESTRICTED BETA-2-ADRENERGIC RECEPTOR

NTera-2/D1 (NT2) is a human teratocarcinoma cell Line which can be cul tured as a dividing population of precursor cells that can be manipula ted with retinoic acid (RA) to yield post-mitotic neurons. Precursor c ells were transfected with the human beta 2 adrenergic receptor, contr olled by the neuronal cell specific rat synapsin-1 promoter. Transfect ed precursor cells did not display elevated expression of the beta 2 a drenergic receptor. Upon differentiation to a neuronal phenotype with RA, beta Syn2 and beta Syn4 (beta 2Syn-NT2; ATCC CRL-12356) displayed elevated beta 2 adrenergic receptor levels, and an elevated coupling t o cAMP production. It was also observed that the elevated expression o f the beta 2 adrenergic receptor in the neuronal NT2 cells resulted in an enhanced level of neuronal differentiation compared to the wild ty pe cells. These results demonstrate that the neuronally restricted exp ression of the human beta 2 adrenergic receptor in NT2 neurons results in increased receptor levels and receptor stimulated generation of cA MP, this may result in the observed improvement in neuronal differenti ation. (C) 1998 Elsevier Science B.V. All rights reserved.