6-OHDA-induced ectopia of external granule cells in the subarachnoid space covering the cerebellum

The present report describes the genesis, development and topographical distribution of ectopic cells of the external granular layer in the subarachnoid space covering the rat cerebellum. Following one intracisternal injection to newborn rats of 100 micrograms 6-hydroxydopamine (6-OHDA), the meningeal cells degenerate and are removed by phagocytosis within 24 h post injection (p.i.), leaving the cerebellar cortex without a pia-arachnoid cover. Defects appear in the basal lamina investing the cerebellar cortex 3 to 5 days p.i., and both external granule cells and 'sprouts' from Bergmann-glia endfeet grow into the subarachnoid space. The latter form large, flat glial lamellae and cover extensive areas of the denuded cerebellar surface, although they do not form a glial scar over the exposed neuropil of the cerebellar cortex. The numbers of ectopic external granule cells increase within the subarachnoid space both by proliferation and a continuous efflux of cells from the cerebellar cortex. They migrate, aggregate, and ultimately develop into granule, stellate and basket cells, the morphology of which is indistinguishable from their counterparts in situ; they make specific afferent and efferent connections, both among themselves and with the underlying cerebellar cortex and brainstem. The distribution of ectopic external granule cells and their derivatives is restricted to the anterior vermal fissures and the vermal-hemispheric junctions. The present results indicate that external granule cells and their derivatives are capable of both differentiating normally and surviving in the subarachnoid space if they become associated with glial cells and establish synaptic connections.     

The effect of retinoids on the activity of the membrane form of galactosyltransferase, studied in an enzyme/liposome model system

In the present study the effect of retinoids on the membrane form of galactosyltransferase was tested. A model system consisting of pure bovine milk galactosyltransferase and phosphatidylserine vesicles was used for this investigation. Retinol, retinal and retinylphosphate were able to overcome the modulating effect of phosphatidylserine, that is, activated the enzyme. Retinoic acid and retinylpalmitate were ineffective in this system.     

Molecular organization of the outer membrane of Salmonella typhimurium different release of lipopolysaccharide from wild type and lipopolysaccharide mutant cells by EDTA treatment

Cells of Salmonella typhimurium wild type and of several well defined lipopolysaccharide mutants were treated with EDTA. The percentage release of lipopolysaccharide and phospholipid was determined. The results obtained show that the release of lipopolysaccharide by EDTA declines along with the gradually diminishing chain length of the lipopolysaccharide, althought the total amount of lipopolysaccharide was found to increase at the same time in the respective mutants. Implications of these findings for the organization of the outer membrane are discussed.     

The bulk of ATP is associated to proteins in the living cell: a release kinetics study

The analysis of the nonionic detergent induced release kinetics of intracellular components is a promising approach to obtain information on the possible molecular interactions inside the living cell. The molecular interactions of ATP were studied by monitoring the nonionic detergent-induced release kinetics of ATP from cultured human cells. The observed rapid mobilization rate in the presence of Triton X 100 and the retarded release in the presence of Brij 58 were in good agreement with the detergent-induced release kinetics of proteins and K+ reported earlier. These data are consistent with the idea that the bulk of ATP is associated to the protein macromolecules of the living cell.     

Covalent linkage of lipoprotein to peptidoglycan is not essential for outer membrane stability inProteus mirabilis

Incubation of hexadecameric glyceraldehyde 3-phosphate dehydrogenase of Scenedesmus obliquus with dithiothreitol caused a transient increase in NADPH-dependent activity. When ATP was also included in the incubation, the induced NADPH-dependent activity was stabilised. The rate of induction of NADPH-dependent activity increased hyperbolically with respect to ATP concentration. The effect of binding of ATP to the enzyme was two-fold; not only did it stimulate the dithiothreitol-promoted formation of an enzyme species with high NADPH-dependent activity it also prevented the inactivation of this species. The high concentration of ATP required for the stimulation of the NADPH-dependent activity compared with those for NADPH suggest that activation by ATP is unlikely to be of physiological significance.     

Novel azulene derivatives for the treatment of erectile dysfunction

Based on the dopamine D₄ receptor partial agonist FAUC 3019, a series of azulenylmethylpiperazines was synthesized and affinities for the monoaminergic GPCRs including dopamine, serotonin, histamine and α-adrenergic receptor subtypes were determined. Ligand efficacies of the most promising test compounds revealed the N,N-dimethylaminomethyl substituted azulene 11 to be the most potent D₄ partial agonist (EC₅₀ = 0.41 nM). This candidate was investigated for its ability to promote penile erection. Applying an in vivo animal model, test compound 11 turned out to stimulate penile erection in male rats with superior potency in low concentrations when compared to apomorphine.     

Bivalent molecular probes for dopamine D2-like receptors

Merging two arylamidoalkyl substituted phenylpiperazines as prototypical recognition elements for dopamine D(2)-like receptors by oligoethylene glycol linkers led to a series of bivalent ligands. These dimers were investigated in comparison to their monomeric analogues for their dopamine D(2long), D(2short), D(3) and D(4) receptor binding. Radioligand binding experiments revealed strong bivalent effects for some para-substituted benzamide derivatives. For the D(3) subtype, the target compounds 32, 34 and 36 showed an up to 70-fold increase of affinity and a substantial enhancement of subtype selectivity when compared to the monovalent analogue 24. Analysis of the binding curves displayed Hill slopes very close to one indicating that the bivalent ligands displace 1equiv of radioligand. Obviously, the two pharmacophores occupy an orthosteric and an allosteric binding site rather than adopting a receptor-bridging binding mode.