Microdialysis of galanin in rat spinal cord: in vitro and in vivo studies.

The release of the neuropeptide galanin was measured with microdialysis in the dorsal horn of the rat spinal cord. Recovery of unlabeled galanin-like immunoreactivity (GAL-LI) in vitro was measured with radioimmunoassay (RIA) and was found to be 1.4-1.5%. In vivo galanin level was close to the detection level of the RIA under basal conditions. The peptide was released in the dorsal horn during electrical stimulation of the sciatic nerve. The nerve was stimulated for 30 min at a stimulus strength that activated A- and C-fibers. Thus, release of galanin in the spinal cord of the rat is possible to measure with the microdialysis technique.

Enhancement of antipsychotic-like effects by combined treatment with the alpha1-adrenoceptor antagonist prazosin and the dopamine D2 receptor antagonist raclopride in rats.

Blockade of central alpha1-adrenoceptors has been implicated as a possible factor contributing to the atypical antipsychotic profile of clozapine. Thus, in the present study we examined the effects of concomitant alpha1-adrenoceptor and dopamine D2 receptor blockade on conditioned avoidance response performance, as an index of antipsychotic-like activity, and on the induction of catalepsy, as a test for extrapyramidal side effect liability, in rats. It was found that pretreatment with the alpha1-adrenoceptor antagonist prazosin (0.2mg kg(-1) s.c.) caused an enhancement of a suppression of conditioned avoidance response in the presence of the dopamine D2 receptor antagonist raclopride (0.05-0.20 mg kg(-1) s.c.). The effect was most prominent at a subthreshold dose of raclopride (0.05 mg kg(-1)). At these doses, prazosin or raclopride by themselves, or in combination, did not produce catalepsy. In addition, pretreatment with prazosin (0.2mgkg(-1) s.c.) did not alter the catalepsy produced by a higher dose of raclopride (1.0 mg kg(-1) s.c.). It is suggested that, in the presence of low dopamine D2 receptor occupancy, additional alpha1-adrenoceptor blockade might improve antipsychotic efficacy, and thereby improve the therapeutic window with regard to parkinsonism.

Structural determination of the O-antigenic polysaccharide from the enterotoxigenic Escherichia coli O147.

The structure of the O-antigenic polysaccharide from enterotoxigenic Escherichia coli O147 has been determined by NMR spectroscopy, and component and methylation analyses. The sequence of the sugar residues could be determined by NOESY and heteronuclear-multiple-bond-connectivity NMR experiments. It is concluded that the polysaccharide is composed of tetrasaccharide repeating units with the following structure: -->4)-beta-D-GalpA-(1-->3)-beta-D-GalpNAc-(1-->2)-alpha-L-Rhap+ ++-(1-->2)-alpha-L-Rhap-(1-->, where Rha represents 6-deoxymannose. The O-antigen of E. coli O147 is identical to the repeating unit of Shigella flexneri serotype 6 lipopolysaccharide, except that the latter contains an O-acetyl group at C3 of the rhamnosyl residue substituted by the N-acetylgalactosamine residue. Immunochemical analyses using a monoclonal antibody specific for the S. flexneri serotype 6 O-antigen showed an identical reactivity with both lipopolysaccharides.