<b>VIP release from human neuroblastoma cells by bifemelane and </b><b>indeloxazine </b>

Abstract

Bifemelane hydrochloride (BFM -HC1) and indeloxazine hydrochloride (IND-HC1) were found to enhance significantly VIP release from human neuroblastoma NB-OK»1. BFMHCl enhanced VIP release from the cells dose-dependently at concentrations of 10-5-10'5" M during 24 h. IND -HC1 at 10"?' M concentration also increased VIP release, but to a lesser extent. VIP content in the cells increased significantly when the cells were incubated with 10'5-10"" M IND -HC1 for 24 h, but no dose-dependence of the effect was observed. Scatchard plot analysis revealed the existence of at least two classes of specific IND-binding sites: one having Kd 1.3 ;.¢M and Bmax 2.5 >< 10"2 fmol/cell and the other having Kd 465 /.tM and Bmax 15 fmol/cell. BFM -HC1 also shared the IND-binding sites with a Ki value of 67 nM. The binding component in solubilized membrane preparation of the NB-OK-1 cells was found to have a molecular mass of 65 kDa. Although further investigation is required to demonstrate that the binding of these drugs to such sites induce directly the release of VIP, the results encouraged us to use the present system to explore the mechanism of VIP release by these drugs.