RETINOIC ACID-INDUCED REGULATION OF NEUROPEPTIDE-Y RECEPTOR EXPRESSION AND FUNCTION IN THE NEUROEPITHELIOMA LINE SK-N-MC

Neuropeptide Y (NPY) acts through specific receptors to inhibit adenyl cyclase and may have a role in neuroblastomas and neuroepitheliomas ( NE) as a regulator of cell growth and differentiation. The authors hav e examined the status of NPY receptors in the NE cell line SK-N-MC and the effect of retinoic acid (RA), a known differentiating agent, on t heir expression and function. Methods: Competitive NPY binding studies were performed on normal and RA-treated cells, followed by Scatchard analysis. NPY receptor function in the absence of or following RA trea tment was determined by the ability of various concentrations of NPY t o attenuate the forskolin-stimulated accumulation of intracellular cAM P. The mitogenic effect of NPY was evaluated by growing normal or RA-t reated cells in the presence of various concentrations of NPY. Results : Scatchard analysis showed a K-d of 2.3 nmol/L and a B-max of 91,000 receptors per cell for untreated cells. RA treatment decreased recepto r expression to 11,700 per cell without a significant change in recept or affinity (3.6 nmol/L). The effect of forskolin was inhibited by NPY in a dose-dependent fashion in both untreated and treated cells indic ating functional receptors in both. NPY stimulates the growth of norma l SK-N-MC cells. NPY stimulated growth was significantly attenuated af ter RA treatment, possibly as a result of decreased NPY receptor expre ssion. Conclusions: Treatment of SK-N-MC cells with RA, a known differ entiating agent, leads to decreased expression of functional NPY recep tors and a concomitant decrease in the mitogenic effect of NPY. This s upports a role for NPY in the pathogenesis of NE. Copyright (C) 1997 b y W.B. Saunders Company.