Effects of the antipsychotic drug haloperidol on the somastostatinergic system in SH-SY5Y neuroblastoma cells

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 (SRIF) receptors, have been shown to localize to lipid rafts. The aim of this 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-3β-ol. These changes were accompanied by a loss of flotillin-1 and Fyn from the lipid rafts. We next studied the functionality of the SRIF receptor. Treatment with haloperidol reduced the inhibitory effect of SRIF 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 SRIF signaling whereas the AC response to forskolin remained elevated. The results show that haloperidol, by affecting cholesterol homeostasis, ultimately alters SRIF signaling and AC activity, which might have physiological consequences.     

Effect of furosemide on the ionic composition of the arterial wall

Furosemide decreased the intracellular H2O, Cl and K content and Cl concentration of dog carotid arteries incubated in normal or high K Krebs (123 mM). Cl loss exceeded K loss in normal Krebs but was of the same magnitude in high K Krebs. The findings are compatible with the inhibition of a neutral K-Cl coupled uptake.     

Molecular characterization and phylogenetic analysis of SpBMP5-7, a new member of the TGF-beta superfamily expressed in sea urchin embryos.

TGF-beta ligands are probably pan-bilaterian in phylogenetic distribution. The family appears to have diversified greatly with the evolution of the vertebrates, but only a few invertebrate deuterostome TGF-beta molecules have so far been isolated. A search for members of this family expressed in sea urchin embryos, using canonical PCR primers, revealed a single-copy gene encoding a new TGF-beta protein. The sequence which it encodes is closely related to those of vertebrate bone morphogenetic proteins (BMPs) 5-7. No additional TGF-beta family members were uncovered other than univin, which had previously been reported.