EFFECTS OF THE ANTIPSYCHOTIC DRUG HALOPERIDOL ON THE SOMASTOSTATINERGIC SYSTEM IN SH-SY5Y NEUROBLASTOMA CELLS.
J Neurochem. 2009 May 11;
Authors: Sánchez-Wandelmer J, Hernández-Pinto AM, Cano S, Dávalos A, Dávalos A, de la Peña G, Puebla-Jiménez L, Arilla-Ferreiro E, Lasunción MA, Busto R
Abstract Antipsychotics are established drugs in schizophrenia treatment which, however, are not free of side effects. Lipid rafts are critical for normal brain function. Several G-protein coupled receptors, such as somatostatin receptors, have been shown to localize to lipid rafts. The aim of the present study was to investigate whether haloperidol treatment affects the composition and functionality of lipid rafts in SH-SY5Y neuroblastoma cells. Haloperidol inhibited cholesterol biosynthesis, leading to a marked reduction in cell cholesterol content and to an accumulation of sterol intermediates, particularly cholesta-8,14-dien-3beta-ol. These changes were accompanied by a lost of flotillin-1 and Fyn from the lipid rafts. We next studied the functionality of the somatostatin receptor. Treatment with haloperidol reduced the inhibitory effect of somatostatin on adenylyl cyclase (AC) activity. On the other side, haloperidol decreased basal AC activity but increased forskolin-stimulated AC activity. Addition of free cholesterol to the culture medium abrogated the effects of haloperidol on lipid-raft composition and somatostatin signaling whereas the AC response to forskolin remained elevated. The results show that haloperidol, by affecting cholesterol homeostasis, ultimately alters somatostatin signaling and AC activity, which might have physiological consequences.
PMID: 19457089 [PubMed - as supplied by publisher]