Nicotinic Autoreceptors Mediating Enhancement of Acetylcholine Release Become Operative in Conditions of "Impaired" Cholinergic Presynaptic Function

Abstract: The existence in the mammalian CNS of release-inhibiting muscarinic autoreceptors is well established. In contrast, few reports have focused on nicotinic autoreceptors mediating enhancement of acetylcholine (ACh) release. Moreover, it is unclear under what conditions the function of one type of autoreceptor prevails over that of the other. Rat cerebrocortex slices, prelabeled with [³H]choline, were stimulated electrically at 3 or 0.1 Hz. The release of [³H]ACh evoked at both frequencies was inhibited by oxotremorine, a muscarinic receptor agonist, and stimulated by atropine, a muscarinic antagonist. Nicotine, ineffective at 3 Hz, enhanced [³H]ACh release at 0.1 Hz; mecamylamine, a nicotinic antagonist, had no effect at 3 Hz but inhibited [³H]ACh release at 0.1 Hz. The cholinesterase inhibitor neostigmine decreased [³H]ACh release at 3 Hz but not at 0.1 Hz; in the presence of atropine, neostigmine potentiated [³H]ACh release, an effect blocked by mecamylamine. In synaptosomes depolarized with 15 mM KCI, ACh inhibited [³H]ACh release; this inhibition was reversed to an enhancement when the external [Ca²⁺] was lowered. The same occurred when, at 1.2 mM Ca²⁺, external [K⁺] was decreased. Oxotremorine still inhibited [³H]ACh release at 0.1 mM Ca²⁺. When muscarinic receptors were inactivated with atropine, the K⁺ (15 mM)-evoked release of [³H]ACh (at 0.1 mM Ca²⁺) was potently enhanced by ACh acting at nicotinic receptors (EC₅₀? 0.6 µM). In conclusion, synaptic ACh concentration does not seem to determine whether muscarinic or nicotinic autoreceptors are activated. Although muscarinic autoreceptors prevail under normal conditions, nicotinic autoreceptors appear to become responsive to endogenous ACh and to exogenous nicotinic agents under conditions mimicking impairment of ACh release. Our data may explain in part the reported efficacy of cholinesterase inhibitors (and nicotinic agonists) in Alzheimer's disease.     

Cloning of Choriocarcinoma Cells Shows That Invasion Correlates with Expression and Activation of Gelatinase A

Implantation and placental development are dependent upon trophoblast invasion of the endometrium. While the villous trophoblast does not display invasive behavior, the extravillous cytotrophoblast is highly invasive. By cloning BeWo choriocarcinoma cells, we have isolated two distinct clones that share similarities with villous and extravillous cytotrophoblasts. When cultured at the surface of a type I collagen gel, BeWo MC-1 cells were not invasive, whereas BeWo MC-2 cells rapidly invaded this matrix. When injected subcutaneously in nude mice, BeWo MC-1 cells developed a localized tumor and BeWo MC-2 cells developed larger tumors with micrometastases. Gelatinase A expression and minute amounts of gelatinase B were detected in the parental cell line and in both clones. However, the parental and the BeWo MC-2 cells secreted 5- to 10-fold more gelatinase A than the BeWo MC-1 cells. Laminin and matrigel stimulated the production of gelatinase A in BeWo MC-2 cells. Type I collagen promoted the conversion of the 72-kDa progelatinase A in an active enzyme only in parental BeWo and in BeWo MC-2 cells. These clones provide an interesting model for studying the complex mechanisms regulating implantation as well as the controlled invasiveness during implantation compared to tumor invasion.     

Biological basis for the management of ‘lugs negra’ (Sarcothalia crispata Gigartinales,Rhodophyta) in southern Chile

The present paper describes growth dynamics in a natural bed of the resource luga negra (Sarcothalia crispata) in Guapilinao, southern Chile (41°57 S, 73°31 W). This resource is currently harvested and exported as raw material for the production of carrageenan. Seasonal variation in biomass, frond size, density and phenology was determined by periodic sampling. Natural recruitment was evaluated on different substrata added to the field; at the same time, substrata were inoculated under greenhouse conditions. Results showed that luga negra has seasonal growth: biomass increased from a minimum in spring to a maximum in mid to late summer. On the other hand, density was minimal in winter (200 ind. m^–2) and increased to 2000 ind. m^–2 in late spring. Peak abundance of mature tetrasporic fronds occurred in late summer, whereas that of cystocarpic fronds occurred in winter. Recruitment began in summer and extended into winter. Survival on different substrata were compared. Gametophytes had better survival rates on clam shells and 5 mm rope while tetrasporophytes had the best survival rate on clam shells and secondarily on boulders.     

Summer biomass of a population of Iridaea cordata (Gigartinaceae,Rhodophyta) from Antarctica

Results of a seasonal study on biomass in an infralittoral population of Iridaea cordata from Terra Nova Bay (Ross Sea, Antarctica) are reported. Thalli were collected during the IX Italian Antarctic Expedition (austral summer 1993–94). The population studied is that living at depths of 4 to 6 m, where the highest density of plants occurred. The highest value of biomass (wet weight 3440 g m^–2) was found at the beginning of summer. In that period 72.5% of biomass was from 128 specimens belonging to weight classes 8 (>16 to 32 g) to 10 (>64 g), corresponding to 13.4% of the population in numbers. Small (<1 g) and medium (1 to 8 g) specimens provided the remaining biomass of 5% and 22.5%, respectively. During the month of January, the number of heavy specimens decreased. At the end of that month biomass reached a minimum of 2225 g m^–2. In February the biomass increased to 3169 g m ^–2, 72% of which was from 120 specimens belonging to weight classes 7 (>8 to 16 g) to 9 (>32 to 64 g), which numerically represented 18.5% of the population. Data showed that biomass depended mainly on the presence of large heavy specimens, even though they were always few in number. Moreover, the occurrence of such large thalli at the beginning of summer suggests that Iridaea cordata continues to grow during the long antarctic winter.     

Nefiracetam (DM-9384) reverses apomorphine-induced amnesia of a passive avoidance response: Delayed emergence of the memory retention effects

Nefiracetam is a novel pyrrolidone derivative which attenuates scopolamine-induced learning and post-training consolidation deficits. Given that apomorphine inhibits passive avoidance retention when given during training or in a defined 10–12h post-training period, we evaluated the ability of nefiracetam to attenuate amnesia induced by dopaminergic agonism. A step-down passive avoidance paradigm was employed and nefiracetam (3 mg/kg) and apomorphine (0.5 mg/kg) were given alone or in combination during training and at the 10–12h post-training period of consolidation. Co-administration of nefiracetam and apomorphine during training or 10h thereafter produced no significant anti-amnesic effect. However, administration of nefiracetam during training completely reversed the amnesia induced by apomorphine at the 10h post-training time and the converse was also true. These effects were not mediated by a dopaminergic mechanism as nefiracetam, at millimolar concentrations, failed to displace either [³H]SCH 23390 or [³H]spiperone binding from D₁ or D₂ dopamine receptor subtypes, respectively. It is suggested that nefiracetam augments molecular processes in the early stages of events which ultimately lead to consolidation of memory.     

Paleobiology of Etruscan populations

A research project on the population biology of ancient Etruscans has recently started. The aim of this multidisciplinary research is the anthropological definition of Etruscan populations, about which little is known. The study of the skeletal remains is expected to lead to the identification of characteristics typical of this group, which will be used to establish affinities and differences with other contemporary Italic populations, as well as with previous and subsequent groups. An outline of the project is presented here, together with an indication of the problems concerning the availability of material. A summary of previous research on Etruscans is also given. In the final section, preliminary results are presented on one aspect of the research presently under way, namely the odontometric study of different groups of Etruscan populations. These results suggest a homogeneity within the groups described under the common label “Etruscans”.     

Distribution of extracellular polysaccharides and flotation of anaerobic sludge

 Extracellular polysaccharides (EPS) were quantified in dense granules and loose flocs by chemical analysis of the uronic acid content. Their distribution within the aggregates was determined by microscopic staining. Granules contained a higher amount of EPS (1–1.6 mg/g volatile suspended solids, VSS) than flocs (0.3 mg/g VSS). In granules approximately 50% of the total amount of EPS was present in a 40-μm-thick zone on the surface. The remainder was dispersed in the rest of the aggregate. In flocs the highest concentration was present in the centre and the EPS layer on the surface was not found. Tests showed that flocculent sludge was very sensitive to flotation, while the studied granules did not float. The lower susceptibility to flotation of granules as compared to flocs was attributed to the presence of the hydrophilic EPS coating that prevents attachment of gas bubbles. Received: 21 November 1995/Received last revision: 15 April 1996/Accepted: 22 April 1996     

Effect of anthropometric characteristics and socio-economic status on physical performances of pre-pubertal children living in Bolivia at low altitude

We have previously observed that 11-year-old children of low socio-economic status (LSES) showed a delayed physical growth of approximately 2 years and developed lower normalized short-term power output than children of high socio-economic status (HSES) of the same age. In contrast, maximal oxygen uptake per unit of fat free mass was no different in either group. The aim of this study was to evaluate the effect of anthropometric characteristics between HSES and LSES prepubertal children in aerobic and anaerobic performance. To compare children of the same body dimensions, 11-year-old boys (n = 30) and girls (n = 31) of LSES and 9-year-old boys (n = 21) and girls (n = 27) of HSES were studied. Anthropometric measurements, (direct test), maximal anaerobic power (P _max, force-velocity test) and mean anaerobic power ( , Wingate test) were determined. In these children having the same body dimensions: mean were the same in LSES and HSES children [1.2 (SD 0.2)1-min^–1];P _max and were lower in LSES subjects [154.0 (SD 33.2) vs 174.6 (SD 38.4) W and 116.3 (SD 23.3) vs 128.2 (SD 28.0) W, respectively]; the linear relationships between and fat free mass were the same in LSES and HSES boys but, in the girls, the LSES group had lower values. For anaerobic performance, the relationships were significantly different: the slopes were the same but LSES values for the both sexes were lower. These results would suggest that factors other than differences in body dimensions alone were responsible for the lower performance of LSES girls and boys. Cultural factors and motor learning, structural and functional alterations of muscle induced by marginal malnutrition have been discussed.