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Biomedical subjects

R J Hitzemann

Publications and source records attributed to R J Hitzemann.

At least 55 records · Page 3Linked to original sources
PubMed1985

Determination of ethanol partition coefficients to the interior and the surface of dipalmityl-phosphatidylcholine liposomes using deuterium nuclear magnetic resonance spectroscopy.

The binding of ethanol-d6 to dipalmityl-phosphatidylcholine liposomes (DPPC) can be separated into two processes, namely, ethanol in the bilayer and on the surface of the bilayer. For the deuterons of the methylene group, the T2 of both bound states is shorter than the respective preexchange lifetime (tau beta) and therefore the amount of ethanol bound to both sites can be determined from the decrease in the methylene intensity resonance in the presence of DPPC. For the methyl resonance, however, only the T2 of deuterons on ethanol bound to the surface is less than its tau beta and the amount of surface bound ethanol-d6 can be determined. Subtraction yields the amount of ethanol bound within the bilayer. The partition coefficient for internally bound ethanol remains constant from 0 to 3.5 m ethanol. Surface binding is, however, highly cooperative.

Ethanol↗
PubMed1985

Specific opioid-amphetamine interactions in the caudate putamen.

Bilateral microinjection of morphine (0.003-3 micrograms/side) into the caudate putamen enhances the behavior induced by the IP injection of 1 mg/kg d-amphetamine phosphate in a dose-related manner. The duration of activity was prolonged and ambulation was changed to d-amphetamine stereotypy, a behavior normally associated with higher doses of d-amphetamine. The opioid activity was stereospecific in that levorphanol was active, whereas dextrorphan was not. The enhancement of d-amphetamine-induced behavior by the opioids was blocked by naloxone. D-ala2-met-Enkephalin also enhanced the amphetamine-induced behavior. This enhancement appears to be specific to the caudate putamen because the oral stereotypy observed appears to be a unique action of amphetamine in this region of the brain.

Amphetamine↗
PubMed1985

Down-regulation of central dopamine receptors in schizophrenia.

CSF homovanillic acid (HVA) levels reflecting central dopamine release and apomorphine-stimulated human growth hormone (HGH) secretion reflecting central dopamine receptor activity were concomitantly determined in 20 schizophrenic patients. There was a strong negative correlation between HVA and HGH levels: high dopamine release was associated with lower HGH responses to dopamine receptor activation by apomorphine. Studies are reviewed which suggest that the presently observed relationship reflects release-mediated down-regulation of central D2 receptors, the dopamine receptor subtype associated with the antipsychotic properties of neuroleptic medication.

Adolescent↗
PubMed1984

Platelet monoamine oxidase activity in the psychoses: relationship to symptoms and lithium response.

The kinetics of platelet monoamine oxidase (MAO) were studied in 100 psychotic and manic patients and 36 controls. No relationship was found between MAO activity and response to lithium in the schizophrenic-like illnesses. However, the data do suggest there is an association between enzyme affinity (Km) and specific symptom clusters. Patients with the low Km variant of platelet MAO are enriched in depressive symptoms, while those with the high Km variant are enriched in manic symptoms.

Adult↗
PubMed1984

Developmental changes in synaptic membrane fluidity: a comparison of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH).

Cortical synaptic plasma membranes were prepared from rats 3, 7, 10, 14, 21, 28 and 120 days of age. Developmental changes in the fluidity of these membranes were assessed using fluorescence polarization techniques. 1,6-Diphenyl-1,3,5-hexatriene (DPH), a probe of the membrane interior, showed a marked developmental increase in polarization, suggesting a developmental decrease in fluidity. The magnitude of the change from day 3 to the adult was the equivalent of lowering the temperature 7 degrees C. The developmental change in DPH polarization was maintained in liposomes (multilamellar vesicles) prepared from membrane total lipid extracts. In contrast to DPH, 1-[4-(trimethylamino)phenyl]6-phenyl-1,3,5-hexatriene (TMA-DPH), a probe of the membrane surface reported no significant developmental effect on polarization for intact membranes; however, TMA-DPH did report a significant increase in polarization for the total lipid extract liposomes. For the intact membranes, both cis- and trans-parinarate, fluorescent probes of the mid-region of the acyl chains, reported significant developmental increases in polarization. The role of gangliosides in the developmental regulation of fluidity was examined. Gangliosides did not appear to play a role in the developmental changes, but they do have a significant effect (increased polarization) on the membrane surface as reported by TMA-DPH. Fluorescence lifetime and heterogeneity analyses were performed for DPH. There was a small but significant increase in probe lifetime during development. Thus, polarization measurements alone underestimated the increases in membrane order. In an attempt to amplify the differences in membrane organization between the developing and adult membranes, we examined the effects of the membrane perturbant ethanol, on DPH polarization at the different ages. No developmental effect on the ethanol-induced fluidization of synaptic membranes was observed.

Age Factors↗
PubMed1984

Physical properties and lipid composition of brain membranes from ethanol tolerant-dependent mice.

DBA/2 mice were made tolerant to and dependent on ethanol by administration of an ethanol-containing liquid diet for 7 days. Fluorescent probe molecules were used to estimate the fluidity and ethanol sensitivity of brain synaptic membranes from these mice. The fluorescence polarization of cis- parinarate , trans- parinarate , and 1,6-diphenyl-1,3,5-hexatriene (probes of the membrane core) and 1-(4- trimethylammoniumphenyl )-6-phenyl-1,3,5-hexatriene (a probe of the membrane surface) was higher in membranes from ethanol tolerant-dependent mice than in membranes from control mice. The decrease in fluorescence polarization produced by in vitro exposure to ethanol was attenuated in membranes from ethanol tolerant-dependent mice when 1,6-diphenyl-1,3,5-hexatriene was used as the probe, but not when 1-(4- trimethylammoniumphenyl )-6-phenyl-1,3,5-hexatriene was used. These results indicate that chronic ingestion of ethanol decreased the fluidity and the ethanol sensitivity of the synaptic membranes. In contrast to the alterations observed with intact membranes, liposomes of lipids extracted from synaptic membranes of control and ethanol tolerant-dependent mice did not differ in their physical properties. Analysis of membrane lipids demonstrated that chronic ethanol treatment selectively decreased the unsaturated acyl groups of phosphatidylserine without altering the acyl composition of other phospholipids or sphingolipids. The amount of each phospholipid was not changed, but membrane cholesterol was decreased by chronic ethanol ingestion. Use of 2-dimensional thin-layer chromatography allowed the quantitation of 10 different gangliosides. The concentrations of these lipids were unchanged in synaptic membranes from ethanol tolerant-dependent mice. Thus, the changes in membrane physical properties produced by chronic ingestion of ethanol may be due, at least in part, to altered acyl composition of phosphatidylserine. The differences observed between intact membranes and extracted lipids suggest, however, that chronic ethanol treatment also produced changes in the lipid arrangement or lipid-protein interactions of the intact membranes.

Alcoholic Intoxication↗
PubMed1984

Gangliosides enhance the membrane actions of ethanol and pentobarbital.

The physical properties of vesicles containing phosphatidylcholine (PC) and gangliosides were evaluated by the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene, trans- parinarate (probes of the lower acyl regions), and 1-(4- trimethylammoniumphenyl )-6-phenyl-1,3,5-hexatriene (a probe of the glycerol backbone and upper acyl regions). Exposure of PC vesicles to ethanol produced a decrease in polarization of fluorescence of these probes, but large concentrations (200-600 mM) were required. Incorporation of 10 mole% rat brain synaptic gangliosides into the PC vesicles enhanced the effect of ethanol by several-fold. Synaptic gangliosides also enhanced the effect of ethanol on vesicles containing cholesterol in addition to PC. Comparison of mono-, di-, tri-, and asialogangliosides , sphingosine, and sphingomyelin indicated the importance of the oligosaccharide moiety, but not the sialic acid residues, in the enhancement of ethanol action by gangliosides. Variation of assay temperature and the acyl composition of the PC demonstrated that gangliosides increased the effects of ethanol only if the lipids were near the phase transition temperature. Gangliosides also produced a marked enhancement of the effect of pentobarbital on fluorescence polarization of probes in PC vesicles. The membrane partioning of pentobarbital was increased by gangliosides, but it was not clear that this increase in drug concentration in the membrane was sufficient to account for the large change in fluorescence polarization. These results suggest that ganglioside content may be an important determinant of the effects of alcohols and barbiturates on biomembranes. In particular, the high drug sensitivity of neuronal membranes may be related to the enrichment of gangliosides in these membranes.

Animals↗
PubMed1983

Developmental changes in synaptic membrane lipid composition and fluidity.

Synaptic membrane enriched fractions were prepared from 7 and 14 day and adult cortical nerve endings. (a) The levels of synaptic membrane phosphatidylcholine decrease 19% during development while the levels of ethanolamine phosphoglycerides increase 21%. (b) On day 7, desmosterol accounts for 33% of the total membrane sterols. With maturity, the desmosterol disappears and the molar sterol/lipid P ratio increases 56%. (c) The fatty acid composition of the membranes change during development. 16:0 decreases 36% while 18:1 increases 49%. 16:1, a minor component of adult membranes, is found in significant quantities in pup membranes. 22:6 (n-3) increases 34% during development while 22:5 (n-6) decreases 59%. (d) The microviscosity of synaptic membranes, as measured by the fluorescence depolarization technique, increases during development. This effect is observed in both intact membranes and bilayers prepared from lipid extracts of the membrane.

Aging↗
PubMed1981

Phosphatidate as a molecular link between depolarization and neurotransmitter release in the brain.

Phosphatidate, a neuronal phospholipid, stimulated the uptake of calcium by nerve terminals isolated from the striatum of rat brain. This effect was not produced by other phospholipids or glycolipids. Phosphatidate, but not other phospholipids, evoked the release of [3H] dopamine from striatal synaptosomes. The magnitude of both effects was similar to that observed after chemical depolarization of the nerve terminals. These results show that phosphatidate is the only membrane lipid component that acts as a functionally competent ionophore and support the suggestion that phosphatidate may serve as a link between depolarization and neurotransmitter release in the brain.

Animals↗
PubMed1981

Membrane fluidity and alcohol actions.

Many studies have demonstrated that the ability of alcohols and other intoxicant-anesthetics to affect biochemical, physiological, and behavioral processes rests in their hydrophobicity. This means that potency is determined by the ability of the drug to move from a water phase into a lipid or membrane phase. In more precise terms, anesthetic effects are correlated with the volume occupied by the anesthetic molecules within the membrane. Although the anesthetic effects, particularly the inhibition of nerve condition, have been used most frequently in establishing this correlation, the intoxicating effects (i.e., ataxia) of a series of alcohols had also been correlated with their membrane partitioning. These results suggest that the intoxicating, as well as anesthetic, effects of ethanol and related drugs are due to their penetrating into hydrophobic regions of nerve membranes. The predominant hydrophobic region of biological membranes is the "sea" of lipid that surrounds "islands" of functional proteins. This leads to the postulate that intoxicant-anesthetics alter the physical properties of membrane lipids and thus affect neuronal function. To evaluate this hypothesis, we must consider the lipid composition of brain membranes, the importance of membrane lipids in neuronal function, the techniques available for the study of membrane physical properties, and the effects of ethanol on nerve membranes.

Animals↗
PubMed1979

Influence of morphine, beta-endorphin and naloxone on the synthesis of phosphoinositides in the rat midbrain.

The effects of morphine, beta-endorphin and naloxone on the initial incorporation of 32Pi and [3H]glycerol into TPI, DPI and PI were measured in discrete subcellular fractions of the rat midbrain. Morphine and beta-endorphin significantly increased microsomal 32PI incorporation into TPI and PI but not DPI. Although neither morphine nor beta-endorphin significantly affected the levels of [3H]TPI or [3H]DPI, both agents significantly increased [3H]PI levels. All of the significant effects induced by morphine were blocked by naloxone treatment and were decreased after chronic morphine administration. However, naloxone treatment alone also mimicked all the effects of morphine except the increased incorporation of [3H]glycerol into PI. It was also found that chronic morphine treatment significantly increased the incorporation of 32Pi into synaptic TPI and DPI. This effect, however, did not show regional specificity being found in both cortical and subcortical synaptic membranes. Overall, the results suggest that the mechanisms of opioid action are closely associated with changes in the turnover of the brain phosphoinositides.

Animals↗
PubMed1978

High-affinity GABA and glutamate transport in developing nerve ending particles.

The high-affinity transport of [3H]GABA and [14C]glutamate was measured in discrete nerve ending fractions isolated from the developing rat cortex, beginning on day 7 postpartum and prepared using discontinuous Ficoll-isotonic sucrose gradients. On day 7 the material sedimenting in the lightest gradient fractions contained the highest density of particles capable of high-affinity transport. With increasing age, the transport sites became progressively associated with more dense particles in the gradient. On day 14, the Vmax values for both [3H]GABA and [14C-A1glutamate transport in the most dense nerve ending fraction were significantly increased over the adult value. This transient increase in the Vmax values disappeared by day 21. While the Km values for both transport systems were constant in all fractions for the adult animal, this was not the case in the developing pup. The Km values in the lightest fractions were significantly greater than those in the more dense fractions, suggesting that different transport systems may be present during development. Electron micrographs of the various fractions were prepared from 7-day and adult animals. These data illustrate that the lightest fractions of the '7-day' gradient are enriched in profiles similar to developing nerve endings. With development, these light fractions become infiltrated with myelin, the immature nerve ending profiles disappear, and the bulk of the nerve endings are found in more dense fractions.

Age Factors↗
PubMed1978

Effects of some conformationally restricted GABA analogues on GABA membrane binding and nerve ending transport.

By using a series of aminocyclopentane- and aminocyclohexanecarboxylic acids, as well as some naturally occurring amino acids, it was possible to determine some aspects of the spatial topography of the GABA membrane binding and transport sites. The NA-independent GABA binding site was found to have a different spatial topography than the Na-dependent binding site in that trans-3-aminocyclopentanecarboxylic acid (trans-3-ACPC) was 7 times more potent than cis-3-ACPC to inhibit Na-independent binding, but only 1.6 times more potent to inhibit Na-dependent binding. The nerve ending GABA transport site was found to be similar to the Na-dependent GABA binding site in that it will accommodate both cis- and trans-3-ACPC. However, the transport site differs from the binding site in that cis-3-aminocyclohexanecarboxylic acid (cis-3-ACHC) is a potent inhibitor of transport but a weak inhibitor of binding. In addition to the differences in spatial characteristics, differences in the subcellular distribution of Na-independent and Na-dependent binding sites were observed. The former were found primarily in the nerve ending-mitochondrial fraction, while the latter were primarily found in the microsomal fraction.

Aminobutyrates↗