RETINOIC ACID REGULATION OF THE VIP AND PACAP AUTOCRINE LIGAND AND RECEPTOR SYSTEM IN HUMAN NEUROBLASTOMA CELL-LINES

Neuroendocrine tumors, neuroblastoma in particular, commonly express t he neuropeptides vasoactive intestinal peptide (VIP) and pituitary ade nylate cyclase activating peptide (PACAP) and their receptors. Retinoi c acid (RA) has been shown to induce differentiation of neuroblastoma cell lines, possibly by augmenting or interfering with neuropeptide au tocrine loops. We sought to determine which receptor gene subtypes are expressed in selected human neuroblastoma cell lines (SH-SY5Y, IMR-32 , and LA-N-5), and the effect of RA on the VIP/PACAP ligand/receptor s ystem. Expression of both PACAP(1) and VIP1/PACAP(2) receptor genes wa s detected by Northern analysis, which characteristically encode Type I (PACAP-preferring), and Type II (bivalent VIP/PACAP) receptors, resp ectively. Binding experiments carried out on LMR-32 cells, using I-125 VIP and I-125 PACAP-27 as tracers, corroborated that both receptor su btypes were expressed. In contrast to RA upregulation of VIP binding ( confirmed here in IMR-32 cells), levels of both receptor mRNAs were re duced after RA treatment. VIP mRNA in each cell line was increased by RA, whereas PACAP mRNA, detected in IMR-32 cells only, was reduced. Th e studies indicate that several components of the VIP/PACAP autocrine system are regulated in neuroblastoma cell lines during RA differentia tion. (C) 1997 Elsevier Science Inc.