Bibliothek

Notizen: —Preparations of synaptosomes (P2) from the telencephalon and from the diencephalon plus optic lobes of the pigeon and from the telencephalon of the rat were used to study the effects of 5-hydroxytryptophan (5-HTP) on (a) the levels of serotonin (5-HT) in nerve endings and (b) the release of 5-HT from nerve endings. The levels of 5-HT were significantly higher (3.21 × 0.35 nmol/g original tissue weight) in the P2 fraction isolated from the telencephalon of pigeons given intramuscular injections of 50mg/kg of d,l-5-HTP in comparison to control values (1.42 ± 0.07). A similar twofold increase was observed with the P2 fraction isolated from the diencephalon plus optic lobes. In addition, the levels of 5-HTP and 5-hydroxyindoleacetic acid also increased significantly in these P2 fractions isolated from pigeons given d,l-5-HTP injections in comparison to values obtained for pigeons given saline injections. In vitro studies using preparations of synaptosomes (from both pigeon and rat) labelled with [3H]5-HT indicated that 0.10 mil l-5-HTP increased the release of [3H]5-HT twofold over control values. A concentration as low as 0.001 mm l-5-HTP was tested on the P2 fraction from the telencephalon of the pigeon and was found to significantly increase the release of [3H]5-HT over control values. This effect by l-5-HTP was blocked if a decarboxylase inhibitor was added to the medium. l-5-HTP at a concentration of 1.5 mm had no apparent effect on the release of [3H]norepinephrine or [3H]dopamine from synaptosomes prepared from the telencephalon of the rat or pigeon. The results are discussed in terms of the role of serotonin in producing certain types of behavioral depressions exhibited by pigeons and rats given injections of 5-HTP.

Notizen: Using the technique of measuring DNP-amino acid methyl esters by gas-liquid chromatography, the distribution of alanine, proline, glycine, GABA, glutamate and aspartate was determined in individual ganglia and the associated nerve bundles between these ganglia after isolation from the nervous system of the lobster, Homarus americanus. The brain or supraesophageal ganglion (27.2 mg) and the next 5 thoracic ganglia (varying from 24 to 10 mg in a rostral–caudal direction) as well as the nerve bundles connecting these ganglia were used. GABA and aspartate values varied the most among the individual ganglia; highest values were found in the second and third thoracic ganglia. The levels of alanine, proline, glycine and glutamate varied very little from ganglion to ganglion; however, the values for these amino acids did exhibit some variability among the individual connectives. The highest value for each was in the nerve bundle between the first and second thoracic ganglion. Glycine was present at the highest level of any of the amino acids whereas GABA was at the lowest level in the individual structures assayed.

Notizen: Abstract— Crude synaptosomal (P2) preparations were obtained from the cerebella of rats in which the granule cell population had been selectively reduced by X-irradiation treatment and from the cerebella of control animals. In the P2 fraction from control cerebella, the level of glutamate was greater than any other of the 5 amino acids measured and was 2-fold higher than taurine, which was present at the next highest level. The content of taurine was slightly higher than that found for aspartate and was 3-fold greater than that observed for GABA. Alanine and glycine were present in the lowest amounts. The levels of glutamate and aspartate were significantly (P 〈 0.05) lower by 25 and 15%, respectively, in the P2 fraction isolated from the X-irradiated cerebella in comparison to control values. The content of taurine, GABA, glycine, and alanine were not changed by the X-irradiation treatment. The uptake of 1.0 μm-l-[3H]glutamate and l-[3H]aspartate was reduced approx 20% by X-irradiation treatment, whereas the uptake of 1.0 μm-[3H]GABA and [3H]taurine was unchanged. A more detailed kinetic analysis of l-[3H]glutamate uptake revealed there was a 20% decrease in the Vmax value with X-irradiation treatment and no change in the apparent Km value.In a second study, the uptake of l-[3H]glutamate, l-[3H]aspartate and [3H]GABA was measured using P2 fractions obtained from the cerebella of rats in which the population of granule, stellate and basket cells had been reduced by X-irradiation treatment. The uptake of 1.0μm-l-[3H]glutamate, l-[3H]aspartate and [3H]GABA was significantly (P 〈 0.05) reduced to 57, 68, and 59%, respectively, of control values. A more detailed kinetic analysis of [3H]GABA uptake revealed no significant change in the apparent Km and a 35% decrease in the Vmax value.The data are discussed in terms of glutamate being the excitatory neurotransmitter released from granule cells and GABA being the inhibitory neurotransmitter released from basket cells.

Notizen: Abstract— The effects of supramaximal electrical stimulation on the metabolism of amino acids and proteins in incubated superior cervical ganglia of the rat were studied by the use of a gas-liquid chromatographic (GLC) assay procedure. Stimulation at 5 Hz for 2 h caused an apparent increase in tissue levels of free amino acids, with alanine, serine, glycine, valine, threonine, isoleucine and aspartate (+ asparagine) most noticeably affected. The amino acid composition (partial) of the TCA-insoluble proteins of resting and stimulated ganglia was approximately the same after 60 min of incubation, but there was less TCA-insoluble protein in the stimulated ganglia. The addition of amino acids (at plasma concentrations) to the standard media had no apparent affect on the amino acid composition of this protein fraction. Stimulation for 0, 5 h initially increased the efflux of alanine, valine, proline and ornithine into the incubation media but prolonged stimulation (for 4–0 h) decreased the efflux of alanine, serine, glycine and isoleucine and increased the efflux of lysine into the incubation media. The leakage of amino acids from the ganglia appeared to be a sodium-dependent process.The incorporation of 14C from [U-14C]glucose into glutamate (+ glutamine) and aspartate (+ asparagine) was greater in stimulated than in resting ganglia. However, the conversion of glutamate carbons from [U-14C]l-glutamate into aspartate was not affected by stimulation. Incorporation of 14C from [U-14C]glucose into glycine and serine was apparently not affected by stimulation during the 60 min of incubation. However, serine was the only amino acid which exhibited a higher specific radioactivity in stimulated ganglia than in resting ganglia incubated for 4 h in standard media. Lithium ions had the apparent specific effect of increasing the labelling with 14C from [U-14C]glucose into ornithine, and increasing the efflux and overall metabolism of serine in the ganglia. Incorporation of 14C from [U-14C]glucose into proteins was lower in the stimulated than in the resting ganglia if compensation was made for the higher radioactivity available in the total free amino acid pool of the stimulated ganglia.The rate of 14C incorporation from [U-14C]glutamate into the TCA-insoluble proteins of resting ganglia was greater when no other amino acids at concentrations approximating plasma levels were added to the bathing media; this rate was lower in stimulated than in resting ganglia.

Notizen: The content of glutamate, GABA, aspartate, glycine and alanine was determined in the cerebellum, brain stem and cerebrum of three different mutant mice which have been named ‘staggerer’, ‘weaver’ and ‘nervous’ on the basis of neurological symptoms. In the ‘staggerer’ and ‘weaver’ mutants there is an almost complete absence of granule cells in the cerebellar cortex while in the ‘nervous’ mutant there is a loss of Purkinje cells (and to a lesser extent a loss of granule cells) in the cerebellar cortex. In the cerebellum of the ‘weaver’ mutant, the content of glutamate was signficantly lower (P 〈 0.025) than control values (8.77 ± 0.76 vs 12.0 ± 1.3 μmol/g tissue wet wt) and the contents of GABA and glycine were significantly greater than normal levels. In the cerebellum of the ‘staggerer’ mutant, the content of glutamate was significantly lower (6.62 ± 0.70 μmol/g) and the contents of glycine and alanine significantly higher than control values. In the cerebrum and brain stem regions of the staggerer mutant, weaver mutant and the normals the contents of the five amino acids were the same. The contents of glycine and alanine in the cerebellum, GARA and glycine in the brain stem and GABA and alanine in the cerebrum of the nervous mutants were higher than control values. The data are discussed in terms of a possible role for glutamate functioning as an excitatory transmitter when released from the cerebellar granule cells.

Notizen: This review summarises evidence for immunomodulatory effect of drugs administered peri-operatively. The clinical significance of the balance of pro- and anti-inflammatory cytokines may be seen in certain disease states, for example, meningococcal meningitis and Lyme arthritis. This balance may be altered peri-operatively. Traditionally, these changes are considered to be due to the stress response of surgery, the response to cardiopulmonary bypass, or endotoxaemia. This review presents in vitro evidence suggesting that drugs modulating this cytokine balance include non-steroidal anti-inflammatory agents, phosphodiesterase inhibitors and opioids, acting through effects on intracellular cyclic nucleotide messenger systems. An important consequence of the pro-inflammatory cytokine activity is increased adhesion of neutrophils. Aspects of this process may be inhibited by avoiding low blood flow states, by reducing adhesion molecule expression (for example by use of pentoxifylline), or by use of negatively charged anions such as heparin. Neutrophil activity is generally depressed by intravenous anaesthetic induction agents, but is enhanced by opioids. Natural killer cell activity, which is involved in immunity against tumour cells and virally infected cells is transiently depressed by volatile anaesthetic agents and opioids. In contrast catecholamines enhance natural killer cell activity. Whereas decrease in immunoglobulin levels occur peri-operatively, this is not thought to be as a result of drugs at clinically used concentrations but rather due to haemodilution.

Notizen: Abstract: The high-affinity uptake of [3H]serotonin, [3H]glutamate, and [3H]-γ-aminobutyric acid (3H]GABA) and the Na+-independent binding of [3H]glutamate and [3H]GABA were studied using spinal cord preparations obtained from normal mongrel dogs and from dogs made paraplegic by midthoracic spinal cord crush. Lumbosa-cral regions of the spinal cord were removed either before (1 week) or after (3 to 8 weeks) onset of spasticity. A myelin-free synaptosomal fraction was obtained by cen-trifugation and used for studying high-affinity uptake and for preparing synaptic plasma membranes for Na+-inde-pendent binding experiments. For the paraplegic groups, the uptake of 30 nM [3H]serotonin was 66 and 18% of control values after 1 and 3 weeks, respectively. Eadie-Hofstee analysis of [3H]serotonin uptake showed a 90% reduction in Vmax for the paraplegic group relative to control values, thereby indicating the expected loss of descending serotonergic pathways. The high-affinity uptakes of 1 μM [3H]glutamate and [3H]GABA were the same in both the control and nonspastic paraplegic groups after 1 week. However, after 3 weeks, the uptakes of [3H]glutamate and [3H]GABA were 60-70% higher for the spastic group than for the control animals. For both amino acids, Eadie-Hofstee plots revealed no difference in Km and higher Vmax for the spastic group relative to control values. After 1 and 3 weeks, the Na+ -independent binding of 5 nM [3H]glutamate was 40-85% higher and the binding of 10 nM [3H]GABA was 40-60% lower for the paraplegic groups relative to the values for the control animals. Scatchard analysis revealed significant changes in Bmax values for both amino acids. Overall, the data indicate an increase in segmental amino acid excitatory influence which occurred when signs of spasticity were evident.

Notizen: To explore the hypothesis that endogenous 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) might be involved in the etiology of alcoholism, its concentration was determined in the striatum and adrenal gland of rats bred selectively for disparate alcohol drinking. The alcohol-naive alcohol-preferring (P) and the high-alcohol-drinking (HAD) lines of rats demonstrated significantly lower striatal and adrenal salsolinol content when compared with the alcohol-non-preferring (NP) and the low-alcohol-drinking (LAD) lines. In the P-line of rats, 4 weeks of free-choice alcohol drinking had no significant effect on striatal salsolinol levels, although adrenal levels of salsolinol were significantly higher. The salsolinol assayed in the striatum of all lines of rats occurred as a racemic mixture of enantiomers that was unchanged following 4 weeks of alcohol exposure. Unlike striatal tissue, the adrenals of alcohol naive P-rats contained significantly more S- than R-salsolinol (ratio S/R = 83/17) and alcohol consumption resulted in the formation of a nearly racemic mixture of enantiomers. These results suggest a role for genetic factors in the formation of endogenous salsolinol and its potential regulation by short-term alcohol intake.

Notizen: Alcohol naive rats from lines genetically selected for high and low alcohol drinking and founded on either Wistar (P/NP lines) and distinct heterogeneous stocks (AA/ANA and replicate HAD/LAD lines) were tested in the explorative cross-maze and the inescapable slip funnel. Rats of the low alcohol-consuming ANA, NP, LAD1 and LAD2 lines all exhibited a shorter latency before initiating exploration of the maze than did their high alcohol-consuming counterparts (66, 51, 33 and 51% of the values for AA, P, HAD1 and HAD2 lines, respectively). Significant line differences were also found with the slip funnel test (AA 〉 ANA for time in a sprawling posture; P 〉 NP but HAD1 〈 LAD1 and HAD2 〈 LAD2 for time escaping), but the directions of line differences were not consistently related to those in alcohol drinking.