Serotonin Inhibits Acetylcholine Release from Rat Striatum Slices: Evidence for a Presynaptic Receptor-Mediated Effect

Rat brain striatum slices were incubated with [3H]choline, perfused with a physiological buffer, and stimulated by perfusion with a K+-enriched buffer for 2 min. The tritium overflow evoked by K+ was decreased by 5-hydroxytryptamine (serotonin, 5-HT) (maximal inhibition 10(-6) M). This effect of 5-HT was mimicked by several agonists (5-methoxytryptamine, N,N-dimethyl-tryptamine, bufotenin) and blocked by serotonergic antagonists (methiothepin, methysergide, cinanserin) but not by haloperidol; methiothepin and methysergide alone slightly increased the K+-evoked overflow of tritium (3H). Inhibition of the tritium release by 5-HT was not suppressed in the presence of tetrodotoxin (TTX) (10(-6) M). These results suggest that 5-HT tonically inhibits acetylcholine (ACh) release from striatal cholinergic neurons by acting on a presynaptic receptor localized on cholinergic terminals.     

Blood genetic marker studies of a sheep-goat hybrid and its back-cross offspring

Summary. Blood samples from a female sheep-goat hybrid and its back-cross male offspring were tested for electrophoretic variants of plasma albumin, transferrin and esterase, and of red cell carbonic anhydrase, nucleoside phosphorylase, NADH-diaphorase, 'X'-protein, superoxide dismutase, malic enzyme and haemoglobin. Red cells were also tested for blood group antigens. Both animals showed variants that could not be attributed to either sheep or goat alone, thus confirming previous chromosomal data that the female was a genuine sheep-goat hybrid.     

Hydrogenosome-Methanogen Assemblages in the Echinoid Endocommensal Plagiopylid Ciliates,Lechriopyla mystax Lynch, 1930 and Plagiopyla minuta Powers, 19331

ABSTRACT. Lechriopyla mystax Lynch, 1930 and Plagiopyla minula Powers, 1933 contain hydrogenosome-methanogen assemblages similar to those reported for other plagiopylid ciliates. These assemblages are stacks of elongate ovoid hydrogenosomes alternating with methanogens; these stacks are surrounded by cisternae of the rough endoplasmic reticulum that are often accompanied by Golgi complexes. The individual methanogens in the larger ciliate, L. mystax, are about four times the volume of those in the smaller ciliate, P. minuta, but both ciliates appear to contain Gram-negative methanococcoid bacteria, possibly Methanoplanus sp. The endoplasmic reticulum-Golgi complex probably plays a significant role in exploitation of the methanogens by the host ciliate.     

Role of chemokines and formyl peptides in pneumococcal pneumonia-induced monocyte/macrophage recruitment

Host-derived chemoattractant factors are suggested to play crucial roles in leukocyte recruitment elicited by inflammatory stimuli in vitro and in vivo. However, in the case of acute bacterial infections, pathogen-derived chemoattractant factors are also present, and it has not yet been clarified how cross-talk between chemoattractant receptors orchestrates diapedesis of leukocytes in this context of complex chemoattractant arrays. To investigate the role of chemokine (host-derived) and formyl peptide (pathogen-derived) chemoattractants in leukocyte extravasation in life-threatening infectious diseases, we used a mouse model of pneumococcal pneumonia. We found an increase in mRNA expression of eight chemokines (RANTES, macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-2, IP-10, monocyte chemoattractant protein (MCP)-1, T cell activation 3, and KC) within the lungs during the course of infection. KC and MIP-2 protein expression closely preceded pulmonary neutrophil recruitment, whereas MCP-1 protein production coincided more closely than MIP-1alpha with the kinetics of macrophage infiltration. In situ hybridization of MCP-1 mRNA suggested that MCP-1 expression started at peribronchovascular regions and expanded to alveoli-facing epithelial cells and infiltrated macrophages. Interestingly, administration of a neutralizing Ab against MCP-1, RANTES, or MIP-1alpha alone did not prevent macrophage infiltration into infected alveoli, whereas combination of the three Abs significantly reduced macrophage infiltration without affecting neutrophil recruitment. The use of an antagonist to N-formyl peptides, N-t-Boc-Phe-D-Leu-Phe-D-Leu-Phe, reduced both macrophages and neutrophils significantly. These data demonstrate that a complex chemokine network is activated in response to pulmonary pneumococcal infection, and also suggest an important role for fMLP receptor in monocyte/macrophage recruitment in that model.     

Synthesis and antiprotozoal evaluation of benzothiazolopyrroloquinoxalinones,analogues of kuanoniamine A

Boc-aminoethylindoloquinone 8, a key intermediate for the building of pentacyclic quinoneimines, analogues of kuanoniamine A, was synthesized by alkylation of 4,7-dimethoxyindole 3 with 1,2-dibromoethane followed by transformation into azide, reduction of the latter with trimethylphosphine in the presence of 2-(tert-butoxycarbonyloximino)-2-phenylacetonitrile and oxydative demethylation of the Boc-amine 6 with silver(II) oxide. Quinone 8 was then treated in situ with the thiazole o-quinodimethane 10 to afford a regioisomeric mixture of the tetracyclic quinones 11. Treatment of the mixture with trifluoroacetic acid and molecular sieves 4-A provided the corresponding quinoneimines 12. Separation of the regioisomers was performed by preparative thin-layer chromatography on silica gel. The structural assignment was made by 2D 1H-13C HMBC correlations performed on the less polar regioisomer 12b. In vitro anti-leishmanial assays showed that the tested compounds possess a good potency towards two Leishmania sp. as well as against a virulent strain of Toxoplasma gondii and without any cytotoxicity against THP-1 cells.     

Rapid Homogenization of Multiple Sources: Genetic Structure of a Recolonizing Population of Fishers

Abstract: Fishers (Martes pennanti) were extirpated from much of southern Ontario, Canada, prior to the 1950s. We hypothesised that the recent recolonization of this area originated from an expansion of the population in Algonquin Provincial Park, which historically served as a refuge for fishers. To test this hypothesis, we created a sampling lattice to encompass Algonquin and the surrounding area, and we collected contemporaneous DNA samples. We sampled fishers from each of 35 sites and genotyped them at 16 microsatellite loci. Using a Bayesian assignment approach, with no a priori geographic information, we inferred 5 discrete genetic populations and used genetic population assignment as a means to cluster sites together. We concluded that the Algonquin Park fisher population has not been a substantial source for recolonization and expansion, which has instead occurred from a number of remnant populations within Ontario, Quebec, and most recently from the Adirondacks in New York, USA. The genetic structure among sampling sites across the entire area revealed a pattern of isolation-by-distance (IBD). However, an examination of the distribution of genetic structure (F_ST/1^- F_ST) at different distances showed higher rates of gene flow than predicted under a strict IBD model at small distances (40 km) within clusters and at larger distances up to 100 km among clusters. This pattern of genetic structure suggests increased migration and gene flow among expanding reproductive fronts.     

Evidence that the decrease in liver glycogen is associated with the exercise-induced increase in IGFBP-1.

The purpose of the present study was to test the hypothesis that the exercise-induced increase in insulin-like growth factor binding protein (IGFBP)-1 is not always linked to a decrease in blood glucose level and to examine whether the decreasing levels of liver glycogen during exercise may be associated with the increase in IGFBP-1. Three groups of rats were submitted to a 70-min treadmill exercise. One group of rats was fed normally, and the two other groups had their food intake restricted by 50% (50% fast) the night before the experiment. One of these two 50% fasted groups of rats was infused (intravenously) with glucose throughout exercise to maintain euglycemia. Exercise in noninfused 50% fasted rats, compared with the normally fed rats, resulted in significantly lower blood glucose (minute 70) and insulin levels, significantly lower liver glycogen content, no change in IGF-I, and significantly higher increases in free fatty acid, glycerol, beta-hydroxybutyrate, and IGFBP-1. Maintenance of euglycemia during exercise in glucose-infused 50% fasted rats reduced to a large extent the decrease in insulin levels but only slightly attenuated the lipid response and the IGFBP-1 response seen in noninfused 50% fasted rats. Comparisons of all individual liver glycogen and IGFBP-1 values revealed that liver glycogen values were highly (P < 0.001) predictive of the IGFBP-1 response during exercise (R = 0.564). The present results indicate that the IGFBP-1 response during exercise is not always linked to a decrease in plasma glucose and suggest that the increase in IGFBP-1 during exercise may be related to the decrease in liver glycogen content.