Ethanol and delta-sleep-inducing peptide: effects on brain monoamines.

The brain content of dopamine (DA) and its metabolites [dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] were the same in rats with different immobilization times in forced swimming test, while the serotonin (5-HT) concentration was higher in high active (HA, immobilization < 2 min) than low active (LA, immobilization > 5 min) animals. Ethanol (2 g/kg, PO) tended to increase the DA level in the striatum and nucleus accumbens in LA rats and decrease the 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentration in HA rats. delta-Sleep-inducing peptide (DSIP) injection reduced the level of 5-HT in the medial prefrontal cortex (MFC) in both groups, did not affect the concentration of DA or DOPAC, but increased HVA in the striatum of HA rats. DSIP injected before ethanol administration augmented the ethanol effects on 5-HT in the MFC and attenuated the action of ethanol on 5-HIAA in the nucleus accumbens. A relationship between the different levels of voluntary alcohol consumption and sensitivity to stress among LA and HA rats and the differences in DA and 5-HT concentrations is suggested. The use of LA and HA rats in developing models for testing of stress-shielding compounds is also described.

The influence of nerve growth factor on the activities of adenylate cyclase and high-affinity GTPase in pheochromocytoma PC12 cell.

The influence of nerve growth factor (NGF) on the activities of adenylate cyclase and high-affinity GTPase in pheochromocytoma PC12 cells was studied. Incubation of cells with nerve growth factor led to a rapid activation of adenylate cyclase accompanied by an inhibition of high-affinity GTPase. By the 10th min of incubation the activity of adenylate cyclase had been reduced 2-fold when compared to the control. The activity of GTPase, however, increased. No significant changes in the cAMP level were detected. The data obtained indicate that NGF interaction with PC12 cells induces changes in the adenylate cyclase system and this process involves G-proteins that regulate the adenylate cyclase activity.

Production and immunohistochemical characterization of primary cultures of human embryo brain cells.

Primary cultures of human embryo brain cells (9-12 weeks of pregnancy) were obtained. The use of selective substrates (poly-L-lysine, poly-L-ornithine, reconstructed collagen) made it possible to obtain neuron-rich (up to 80%) cultures viable for no less than 30 days. The highest selectivity with respect to neurons was observed when reconstructed collagen was used. Cell types present in the cultures were identified immunohistochemically using antibodies against glial fibrillary acidic protein, galactocerebroside, fibronectin and neurofilaments. The dynamics of cell growth under different cultivation conditions was studied. Cells in culture have been found to preserve the ability to release neurotransmitters (dopamine, norepinephrine and serotonin). Such primary cultures can serve as a suitable model for studying human brain biochemistry in vitro.

The effect of amine structure on complexation with lasalocid in model membrane systems. II. Ionophore selectivity for amines in lipid bilayers and at oil/water interfaces.

The ionophore antibiotic X-537A (lasalocid) transports biogenic amines across biological and artificial membranes. The major portion of amine flux (greater than 99%) occurs as a 1:1 neutral complex. The rank order of ionophore selectivity was determined for lipid bilayer membrane transport of amines based on a comparison of permeability coefficients: p-tyramine approximately beta-phenylethylamine approximately amphetamine greater than methamphetamine greater than dopamine greater than phenylephrine approximately metanephrine greater than norepinephrine greater than epinephrine. This rank order is in agreement with results obtained from partitioning measurements which were carried out in parallel to the bilayer membrane experiments. A correlation between amine structure and binding characteristics has been developed.

The effect of amine structure on complexation with lasalocid in model membrane systems. I. Identification of charged complexes in lipid bilayer membranes.

The electrical properties of X-537A (lasalocid) doped lipid bilayer membranes were studied in the presence of a series of nine biogenic amines which contain beta-phenylethylamine as the basic structural unit. The ionophore antibiotic was found to form charged complexes within the membrane during the transport of some of the amines. The dependence of membrane conductance on the concentration of ionophore and amine was studied. The amines are divided into three classes according to the nature of the complexes formed: (1) charged complex involving two ionophores (phenylephrine, metanephrine, and amphetamine); (2) charged complex containing three ionophores (dopamine, norepinephrine and epinephrine); and (3) no charged species formed (p- and m-tyramine and beta-phenylethylamine).

Cyclodepsipeptides as chemical tools for studying ionic transport through membranes.

This paper reports a study of the chemistry of valinomycin, enniatins and related membrane-active depsipeptides that increase alkali metal ion permeability of model and biological membranes. The antimicrobial activity of these compounds and their effect on membranes has been correlated with their cation-complexing ability. The complexing reaction has been studied by spectropolarimetric and conductimetric methods. Nuclear magnetic resonance, optical rotatory dispersion, and infrared spectrophotometric studies have revealed the coexistence of conformers of the cyclodepsipeptides in solution and have led to elucidation of the spatial structure of valinomycin, enniatin B and their K(+) complexes. The effect of the conformational properties of the cyclodepsipeptides on their complexation efficiency and selectivity, surface-active properties and behavior towards phospholipid monolayers, bimolecular phospholipid membranes and a number of biological membrane systems has been ascertained. The studies have clearly shown the feasibility of using cyclodepsipeptides with predetermined structural and conformational parameters as chemical tools for membrane studies. it is suggested that the principle of conformation-dependent cation binding through iondipole interactions may possibly lie at the basis of the mode of action of systems governing the natural ion permeability in biological membranes.