Retinoic acid-induced regulation of neuropeptide Y receptor expression and function in the neuroepithelioma line SK-N-MC.

Abstract:

UNLABELLED: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 have 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 their 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 treatment was determined by the ability of various concentrations of NPY to attenuate the forskolin-stimulated accumulation of intracellular cAMP. The mitogenic effect of NPY was evaluated by growing normal or RA-treated cell in the presence of various concentrations of NPY. RESULTS:Scatchard analysis showed a Kd of 2.3 nmol/L and a Bmax of 91,000 receptors per cell for untreated cells. RA treatment decreased receptor expression to 11,700 per cell without a significant change in receptor affinity (3.6 nmol/L). The effect of forskolin was inhibited by NPY in a dose-dependent fashion in both untreated and treated cells indicating functional receptors in both NPY stimulates the growth of normal SK-N-MC cells. NPY stimulated growth was significantly attenuated after RA treatment, possibly as a result of decreased NPY receptor expression. CONCLUSIONS:Treatment of SK-N-MC cells with RA, a known differentiating agent, leads to decreased expression of functional NPY receptors and a concomitant decrease in the mitogenic effect of NPY. This supports the role for NPY in the pathogenesis of NE.

journal_name

J Pediatr Surg

authors

Shorter NA,Pence JC

doi

10.1016/s0022-3468(97)90014-2

subject

Has Abstract

pub_date

1997-05-01 00:00:00

pages

721-3

issue

5

eissn

0022-3468

issn

1531-5037

pii

S0022-3468(97)90014-2

journal_volume

32

pub_type

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