bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Relevant Gas Pressure on the Properties of Ionplated Ta2O5 Films. Einfluss relevanter Gasdrücke auf die Eigenschaften ionenplattierter Ta2O5 Schichten
Authors: Schlichtherle S. , Huber D. , Pulker H.K.
Published: April 2003

Moderne optische Vielschichtsysteme fordern hohe Schichtstabilität, geringe mechanische Schichtspannungen und kleinste optische Verluste der sich aufbauenden Einzelschichten. Die gängige industriell genutzte Methode zur Verminderung von mechanischen Schichtspannungen und optischer Rest‐Absorption ist eine Wärmebehandlung nach dem Beschichtungsvorgang. Ziel dieser Arbeit ist eine deutliche Reduktion der genannten Kenngrößen durch die Variation des Arbeits‐ als auch Reaktivgas Partialdruckes ohne Wärmebehandlung der Substrate nach der Beschichtung.

Dafür wurden Tantalpentoxid–Schichten mittels Reaktiven Niedervolt–Hochstrom‐Ionenplattieren (RLVIP) auf ungeheizte Kieselglas–Substrate (Suprasil®) aufgebracht. Diese 200 nm dicken Metalloxid–Schichten wurden auf deren optische Eigenschaften (Brechungsindex n und optischer Absorption Koeffizient k) und auch auf deren mechanische Eigenschaften (Dichte ρ und Schichtspannung σ) in Abhängigkeit vom Arbeitsgas‐Partialdruck (Ar) und Reaktivgas‐Partialdruck (O2) untersucht.

Die Experimente zeigten eine deutliche Korrelation zwischen Schichtspannung, Brechungsindex bzw. Dichte der Schicht. Für niedere Gesamtdrücke wurden hohe Brechungsindizes und hohe intrinsische Schichtspannungen ermittelt. Die Dichte der Schicht, der Brechungsindex und auch die Schichtspannung wurden bei erhöhtem Gesamtgasdruck verringert. Die optische Restabsorption zeigte einen direkten Zusammenhang mit dem Sauerstoffpartialdruck. Durch das Zusetzen von mehr Sauerstoff zum Ar/O2 – Gasgemisch konnte die optische Restabsorption drastisch gesenkt werden.
Foraging behaviour of the hermit crab Clibanarius erythropus in a Mediterranean shore
Authors: Benvenuto Chiara , Sartoni Gianfranco , Gherardi Francesca
Published: April 2003

Field studies were carried out along a Mediterranean rocky shore to describe the foraging behaviour of the hermit crab Clibanarius erythropus, a common intertidal Diogenidae. The spatial strategy adopted during foraging activity was investigated through monitoring the movement of ten individuals, each followed for two hours. This revealed that hermit crabs maximized the space explored while in search of food and that shell type was one factor influencing the extent of movement. The evaluation of hermit abundance on different algal substrates provided clues to understanding the pattern of food utilization. This study shows that ‘generalist’ hermit crabs display a certain degree of selectivity, mostly foraging on assemblages of filamentous algae and corticated macrophytes. The conclusion is that C. erythropus selects substrates where good foraging can occur; whether hermit crabs eat within the selected substrates every food item they encounter or select food at the level of individual items is still an unanswered question.
In situ observations of predatory feeding behaviour of the galatheid squat lobster Munida sarsi using a remotely operated vehicle
Authors: Hudson Ian R. , Wigham Benjamin D.
Published: April 2003

During remotely operated vehicle operations on the UK continental shelf to the west of Shetland (60°6′N 4°4′W) at a depth of 400 m, Munida sarsi, a common benthic crustacean was observed actively preying on the northern krill Meganyctiphanes norvegica. Video footage shows the individual using its chelipeds to catch prey items as they swarm around its burrow. These initial observations indicate that predation forms a new feeding strategy for a species previously believed to be an active scavenger.
Distributional and Biological Aspects of Copepods at Hydrothermal Vents on the Juan de Fuca Ridge, north-east Pacific ocean
Authors: Tsurumi Maia , de Graaf Ramona C. , Tunnicliffe Verena
Published: April 2003

The abundance patterns of copepods on the Juan de Fuca Ridge was examined. One species was studied in detail. Twelve non-parasitic species are recorded from the Juan de Fuca, but only three dirivultid species and some unidentified harpacticoids are abundant in collections. Densities are estimated at 0·5 copepod cm−2 on vestimentiferan tubes to over 8 cm−2 on chimney surfaces. Aphotopontius forcipatus is most abundant at new vents and Benthoxynus spiculifer is most abundant at mature vents. Vents with reduced or undetectable fluid flow have higher diversity of copepod fauna.  The life cycle of the siphonostome Stygiopontius quadrispinosus begins with a centrolecithal egg brooded singly or doubly on the female. Hatching and naupliar stages are unknown in benthic samples. The preadult stage (copepodite V) recruits to the vent habitat. Pre-adult males attach to pre-adult females and fertilize at the final copepodite VI moult. As the sex ratio is highly skewed in favour of females, males probably inseminate many females and there may be mate competition in populations where males are rare. Reproduction is probably continuous or semi-continuous. Abundance is greatest on sulphide edifices near the points of hot water egress. This copepod co-occurs with the alvinellid polychaete Paralvinella sulfincola.
The risk of being at the top: foot-cropping in the New Zealand cockle Austrovenus stutchburyi
Authors: Mouritsen Kim N. , Poulin Robert
Published: April 2003

The common phenomenon of sublethal predation in soft-bottom bivalves usually involves nipping of siphons. Here we show that foot cropping, hitherto documented only in Donax spp., is widespread in the New Zealand cockle Austrovenus stutchburyi (Veneridae). Depending on the locality, cropping frequency ranged between 14 and 34% of cockles, and the average proportion of the foot area cropped ranged between nine and 21%. Estimates of biomass lost to croppers at the time of sampling varied between 235 and 2040 mg ww m−2. It is emphasized that foot cropping in Austrovenus is likely to affect the population dynamics of the cockles.
Food and feeding habits of jumbo squid Dosidicus gigas (Cephalopoda: Ommastrephidae) from the Gulf of California, Mexico
Authors: Markaida Unai , Sosa-Nishizaki Oscar
Published: April 2003

Stomach contents of 533 jumbo squid, Dosidicus gigas, ranging between 14·5 and 87·5 cm dorsal mantle length were collected on a monthly basis in the central Gulf of California from November 1995 to April 1997. Fish prey were identified by sagittal otoliths, cephalopods by beaks and crustaceans by exoskeletal features. The diet was dominated by Benthosema panamense, an abundant near-shore nyctoepipelagic myctophid that forms dense aggregations. Another myctophid, Triphoturus mexicanus, several micronektonic squid, pelagic red crab and small pelagic fish such as northern anchovy and Pacific sardine played a secondary role. The largest differences in diet were due to spatial and monthly changes, while differences regarding squid size or sex were smaller. Prey size (averaging 5–7 cm) and prey number did not vary with size of jumbo squid. Jumbo squid in the slopes of the Guaymas basin feed on abundant schooling mesopelagic micronekton of annual nature with a quick response to environmental changes, which could partly explain the large annual fluctuations of this commercial resource.
Comparison of two Methods for Measuring Filtration Rate in Filter Feeding Bivalves
Authors: Navarro J.M. , Velasco L.A.
Published: April 2003

The filter feeding bivalves Mulinia edulis and Mytilus chilensis, were exposed to a broad spectrum of concentrations and qualities of seston in order to compare the results of filtration rates measured volumetrically and gravimetrically, by both the traditional clearance method of Coughlan (1969) and the biodeposits method. Filtration rates, measured gravimetrically by both methods, tended to give similar results for both species, increasing with increase in seston and with decrease in seston organic content. With volumetric measurements, the filtration rates for both species also increased with the concentration of seston, however, in Mulinia edulis, the effect of the organic content of the food was less than that observed using gravimetric units, which is seen in the smaller slope of the regression equation (TFRv=−0·49). In the case of Mytilus chilensis there was no verifiable effect of the quality of the food on the filtration rate when expressed on a volume basis. The filtration rates of Mulinia and Mytilus measured by two methods and two units showed a similar behaviour with increase in the concentration of seston.
Quantitative aspects of feeding of chaetognaths in the eastern Mediterranean pelagic waters
Authors: Kehayias George
Published: April 2003

The diet of all chaetognath species found in a broad pelagic area of the eastern Mediterranean was investigated through gut content analysis. Eight chaetognath species were recovered from four depth intervals between 0 to 300 m in the Ionian, Cretan and Rhodes Seas and in the Cretan Passage. The mean food containing ratio (FCR) value for all chaetognaths combined was 0·048. Copepods comprised nearly 65% of the total food items consumed. The epipelagic species Sagitta enflata, Sagitta serratodentata atlantica, Sagitta bipunctata and Sagitta minima fed mainly in the 0 to 50 m surface layer, while the mesopelagic species Sagitta lyra, Sagitta decipiens, Sagitta hexaptera and Krohnitta subtilis fed in deeper layers. Sagitta s. atlantica showed the highest mean FCR in the integrated water column (0 to 300 m) of the whole sampling area. The estimated impact of chaetognath predation on copepod communities ranged from 0·3 to 7·8% of the copepod standing stock, and was higher in the Ionian Sea and the Cretan Passage than in the Cretan and Rhodes Seas. Sagitta s. atlantica, S. lyra, and S. decipiens had the most important predation impact among the eight chaetognath species found in the 0 to 50 m, 50 to 100 m and 100 to 300 m depth layers respectively.
HPLC analysis of algal pigments to define diet of sea urchins
Authors: Haug Emmanuelle , Guillou Monique , Connan Solène , Goulard Fabienne , Diouris Marcel
Published: April 2003

A method for a qualitative analysis of sea urchin diet is based on the characterization of the photosynthetic pigment indices of the major algal groups in the sea urchin gut. The pigments were separated by reverse-phase high performance liquid chromatography (RP-HPLC). This study demonstrated that HPLC is a better method to estimate chlorophyll-a in the gut contents than the conventional spectrophotometric methods which overestimate the amounts by including chlorophyll-a breakdown products. Three sea urchins species, Paracentrotus lividus, Psammechinus miliaris and Sphaerechinus granularis, settled on the loose-lying coralline algae (maerl) in the Bay of Brest (France), were used in this study. The algal pigments identified within the gut contents included chlorophylls-a, -b, -c, fucoxanthin, lutein, βε-carotene and ββ-carotene. The presence of chlorophylls and carotenoid biomarkers was used to characterize the three algal groups: Rhodophyceae, Chlorophyceae, Phaeophyceae in estimating sea urchin diet. The pigment analysis reported here demonstrated that the three species of sea urchins investigated mainly consumed Rhodophyceae which dominate the epibenthic flora in the study area.
Feeding habits of the Order Pleuronectiformes and its relation to the sediment type in the north Irish Sea
Authors: Amezcua F. , Nash R.D.M. , Veale L.
Published: April 2003

The diets of scaldfish Arnoglossus laterna, dab Limanda limanda, lemon sole Microstomus kitt, long rough dab Hippoglossoides platessoides, solenette Buglossidium luteum, thickback sole Microchirus variegatus, plaice Pleuronectes platessa, witch Glyptocephalus cynoglossus and Dover sole Solea solea in the Irish Sea were determined for March and October 1997 and 1998 and compared. Similarities in diets were examined using multivariate analyses. In general, there were differences in diet between species and generally the diets were similar within a species. Smaller individuals tended to have a similar diet. There were seasonal changes in the diets of individual species. Likewise, the overlap in diets between species changed between seasons and to a certain extent between sediment types.
The diet and consumption of dominant fish species in the upper Scheldt estuary, Belgium
Authors: Maes Joachim , de Brabandere Loreto , Ollevier Frans , Mees Jan
Published: April 2003

Seasonal changes in the diet composition and trophic niche overlap were examined for the dominant members of the fish assemblage of the turbid low-salinity zone of the Scheldt estuary (Belgium). Samples of fish were taken in the cooling water of a power plant. Juveniles of eight species dominated the fish assemblage: two goby species, herring, sprat, bass, flounder, eel and pikeperch. Together, they had preyed upon 31 different prey taxa. Calanoid copepods and hyperbenthic mysids were the most important prey items with macrobenthic invertebrates being largely ignored. Pair-wise comparisons of trophic niche overlap showed that, in general, niche overlap between individuals of the same species was significantly higher than overlap between individuals from different species, suggesting that the available food resources were partitioned. The total annual prey consumption by the dominant fish species was estimated at 610 mg ash-free dry weight m−3.
Role of kairomones in feeding interactions between seahorses and mysids
Authors: Cohen P.J. , Ritz D.A.
Published: April 2003

Big-bellied seahorses, Hippocampus abdominalis (Chordata: Syngnathidae), feed predominantly on swarming mysids in southern Tasmania. We tested the possibility that kairomones mediate this predator/prey interaction. ‘Fish water’ was prepared by holding one seahorse in 4 l of seawater for 1 h and using this water within 1 h to test for presence of kairomones. One ml of this water pipetted into a tank containing five mysids, Paramesopodopsis rufa (Arthropoda: Mysidacea), induced a significantly increased number of tailflips (mysid escape response) compared with control seawater. The same effect was seen whether seahorses were fed or starved immediately before the experiment. This effect was not seen when realistic concentrations of excretory products, either ammonium hydroxide or urea, were used instead of fish water. When seahorses were kept in visual contact with mysid prey, but unable to capture them, subsequent testing of the ‘fish water’ in the same way as above did not produce a significant increase of tailflipping in mysids. Thus it appears that, when attacking, seahorses can suppress release of kairomones in order to remain chemically inconspicuous to their prey. This is the first demonstration of this phenomenon. When mysids in a cohesive swarm (65 or 100 individuals) were exposed to ‘fish water’, no significant anti-predator response i.e. decrease in swarm volume, could be detected. We interpret these results to indicate the greater vulnerability of mysids when not in social groupings (swarm or school) and the higher likelihood of an energetic response (particularly tailflipping) to a threat.
Diet of harbour seals (Phoca vitulina) in Mull and Skye (Inner Hebrides, western Scotland)
Authors: Pierce G.J. , Santos M.B.
Published: April 2003

Data on the diets of harbour seals (Phoca vitulina) from two islands in the Inner Hebrides (Scotland, UK) based on collections of faecal samples made in 1993 and 1994 are presented. The diet included a range of fish and cephalopod species, of which the most important were gadoids, particularly whiting (Merlangius merlangus), along with pelagic scad (Trachurus trachurus) and herring (Clupea harengus). There were significant temporal and spatial (between-island) differences in diet. The relatively high importance of pelagic species and the low importance of sandeels (Ammodytidae) is consistent with previous studies on grey seals (Halichoerus grypus) in the Inner Hebrides but differs from studies based in other parts of Scotland.
Examination of the stomach contents from a Mediterranean sperm whale found south of Crete, Greece
Authors: Roberts Stephen M.
Published: April 2003

The stomach contents from a male sperm whale, Physeter macrocephalus, first located floating a short distance off the south coast of Crete were examined. The remains within the stomach consisted almost exclusively of cephalopod mandibles, or beaks, though other material was found including a piece of rigid plastic mesh. Of the beaks found, 1714 were upper beaks and 2178 were lower beaks, that were used to identify the species. A total of seven species was identified, all of which have been previously recorded in the eastern Mediterranean though are rarely caught by man. Of these Histioteuthis bonnellii was found to be the most important species in terms of both weight and numbers. Although it must be borne in mind that the whale may not have followed its normal feeding habits prior to its premature death, an important insight into its prey items can be revealed. This is the first documented account of the stomach contents of a sperm whale from the Mediterranean, and helps to complete a global record of sperm whale diets.
Involvement of glutamate and γ‐amino‐butyric acid receptor systems on gastric acid secretion induced by activation of κ‐opioid receptors in the central nervous system in rats
Authors: Minowa Sachie , Ishihara Satomi , Tsuchiya Shizuko , Horie Syunji , Watanabe Kazuo , Murayama Toshihiko
Published: April 2003

Various neurotransmitters in the brain regulate gastric acid secretion. Previously, we reported that the central injection of κ‐opioid receptor agonists stimulated this secretion in rats. Although the existence of κ1–κ3‐opioid receptor subtypes has been proposed, the character is not defined. We investigated the interactions between κ‐opioid receptor subtypes and glutamate, γ‐amino‐butyric acid (GABA) or 5‐hydroxy tryptamine (5‐HT) receptors in the rat brain.

Gastric acid secretion induced by the injection of U69593 (8.41 nmol, a putative κ1‐opioid receptor agonist) into the lateral cerebroventricle was completely inhibited by the central injection of 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 10.9 nmol, an antagonist for non‐N‐methyl‐D‐aspartate (non‐NMDA) receptors) and by bicuculline infusion (222 μg kg−1 per 10 min, i.v., GABAA receptor antagonist). The secretion induced by bremazocine (8.52 nmol, a putative κ2‐opioid receptor agonist) was inhibited by bicuculline infusion, but not by CNQX. The secretion induced by naloxone benzoylhydrazone (224 nmol, a putative κ3‐opioid receptor agonist) was slightly and partially inhibited by CNQX and bicuculline.

Treatment with CNQX and bicuculline inhibited gastric acid secretion induced by the injection of dynorphin A‐(1‐17) into the lateral, but not the fourth, cerebroventricle. Antagonists for NMDA, GABAB and 5‐HT2/1C receptors did not inhibit the secretions by κ‐opioid receptor agonists.

In rat brain regions close to the lateral cerebroventricle, κ‐opioid receptor systems (κ1>κ3≫κ2) are regulated by the non‐NMDA type of glutamate receptor system, and κ1‐ and κ2‐opioid receptor systems are regulated by the GABAA receptor system. The present findings show pharmacological evidence for κ‐opioid receptor subtypes that regulate gastric acid secretion in the rat brain.

British Journal of Pharmacology (2003) 138, 1049–1058. doi:10.1038/sj.bjp.0705082
Interactions between adenosine and metabotropic glutamate receptors in the rat hippocampal slice
Authors: Shahraki Ali , Stone Trevor W
Published: April 2003

We have examined excitatory postsynaptic potentials and paired‐pulse interactions in rat hippocampal slices to obtain more information about the site and mechanism of interactions between metabotropic glutamate receptors and adenosine receptors.

The results show that the suppression of adenosine sensitivity is explained by a selectively reduced responsiveness to A1 receptor stimulation, and does not involve any facilitation of A2A adenosine receptors, since it can be obtained in the absence of endogenous adenosine and is not prevented by the A2A receptor blocker ZM241385.

The glutamate receptors involved are of the group I class since the suppression of adenosine sensitivity is produced by ACPD and the group I selective compound DHPG. Furthermore, the effects of DHPG could be prevented by LY367385, a selective antagonist at the mGlu1a subtype of group I receptors. The selective antagonist at mGlu5 receptors, SIB1893, did not prevent the suppression of adenosine sensitivity by DHPG. Blockade of the DHPG/adenosine interaction was also obtained by superfusion with the protein kinasae C inhibitor chelerythrine.

Since the suppression of adenosine responses by metabotropic receptor agonists was seen in the paired‐pulse paradigm, we conclude that the observed interactions occur at the level of the presynaptic terminals.

The interaction with adenosine receptors is not specific, but applies also to a suppression of responses mediated by the GABAB receptor agonist baclofen.

We conclude that activation of the mGlu1a subtype of receptor can suppress responses mediated via adenosine A1 receptors, probably by activating protein kinase C. Since the changes induced by metabotropic glutamate receptor agonists last for at least 60 min, the data also imply that these interactions could play an important role in changes of synaptic function long after even transient increases of glutamate release in the CNS.

British Journal of Pharmacology (2003) 138, 1059–1068. doi:10.1038/sj.bjp.0705083
Analysis of molecular determinants of affinity and relative efficacy of a series of R‐ and S‐2‐(dipropylamino)tetralins at the 5‐HT1A serotonin receptor
Authors: Alder J Tracy , Hacksell Uli , Strange Philip G
Published: April 2003

Factors influencing agonist affinity and relative efficacy have been studied for the 5‐HT1A serotonin receptor using membranes of CHO cells expressing the human form of the receptor and a series of R‐and S‐2‐(dipropylamino)tetralins (nonhydroxylated and monohydroxylated (5‐OH, 6‐OH, 7‐OH, 8‐OH) species).

Ligand binding studies were used to determine dissociation constants for agonist binding to the 5‐HT1A receptor:

Ki values for agonists were determined in competition versus the binding of the agonist [3H]‐8‐OH DPAT. Competition data were all fitted best by a one‐binding site model.

Ki values for agonists were also determined in competition versus the binding of the antagonist [3H]‐NAD‐199. Competition data were all fitted best by a two‐binding site model, and agonist affinities for the higher (Kh) and lower affinity (Kl) sites were determined.

The ability of the agonists to activate the 5‐HT1A receptor was determined using stimulation of [35S]‐GTPγS binding. Maximal effects of agonists (Emax) and their potencies (EC50) were determined from concentration/response curves for stimulation of [35S]‐GTPγS binding.

Kl/Kh determined from ligand binding assays correlated with the relative efficacy (relative Emax) of agonists determined in [35S]‐GTPγS binding assays. There was also a correlation between Kl/Kh and Kl/EC50 for agonists determined from ligand binding and [35S]‐GTPγS binding assays.

Simulations of agonist binding and effect data were performed using the Ternary Complex Model in order to assess the use of Kl/Kh for predicting the relative efficacy of agonists.

British Journal of Pharmacology (2003) 138, 1129–1139. doi:10.1038/sj.bjp.0705085
Effect of theophylline and specific phosphodiesterase IV inhibition on proliferation and apoptosis of progenitor cells in bronchial asthma
Authors: Wang Chun‐Hua , Lin Horng‐Chyuan , Lin Chien‐Huang , Yu Chih‐Teng , Liu Su‐Ling , Huang Kuo‐Hsiung , Chung Kian Fan , Kuo Han‐Pin
Published: April 2003

Theophylline possesses anti‐inflammatory activities in asthma. We examined whether theophylline and agents that modulate cyclic AMP can determine the survival and proliferation of progenitor cells.

Progenitor cells from the blood of normal and asthmatic subjects were cultured for 14 days in methylcellulose with GM‐CSF, stem cell factor, IL‐3 and IL‐5. Apoptosis was measured by flow cytometry of propidium‐iodide‐stained cells.

A greater number of colonies with a higher proportion of cells of eosinophil lineage from asthmatics compared to normal subjects were grown. Theophylline (at 5 and 20 μg ml−1) significantly inhibited colony formation and increased apoptotic cells in asthmatics compared to control. Salbutamol (0.1, 1, 10 μM), dibutyryl‐cAMP (0.1, 1 mM) and rolipram (0.1, 1 mM), a phosphodiesterase IV inhibitor, also dose‐dependently decreased colony numbers and increased apoptosis of progenitor cells from asthmatics.

There was no significant effect of theophylline, db‐cAMP, salbutamol or rolipram on colony formation or the survival of progenitor cells from normal subjects. AMP did not affect the colony formation and apoptosis. Expression of Bcl‐2 protein on progenitor cells of asthma was downregulated by theophylline, salbutamol, db‐cAMP and rolipram.

Theophylline and rolipram decreased colony formation committed to the eosinophil lineage, together with an increase in apoptosis through an inhibition of Bcl‐2 expression effects that may occur through cAMP. The anti‐inflammatory properties of theophylline include an inhibition of circulating progenitor cells.

British Journal of Pharmacology (2003) 138, 1147–1155. doi:10.1038/sj.bjp.0705131
Interactions of taurine and structurally related analogues with the GABAergic system and taurine binding sites of rabbit brain
Authors: Frosini Maria , Sesti Casilde , Dragoni Stefania , Valoti Massimo , Palmi Mitri , Dixon Henry B F , Machetti Fabrizio , Sgaragli Giampietro
Published: April 2003

The aim of this study was to find taurinergic compounds that do not interact with brain GABA ergic systems.

Washed synaptic membranes (SM) from whole rabbit brain were able to bind [3H]muscimol. Saturation experiments of the binding of [3H]GABA to GABAB receptors showed that SM possess two binding components; twice Triton X‐100‐treated SM contained 0.048 mmol endogenous taurine/kg protein and bound [3H]taurine in a saturable manner (Kd=249.0±6.3 nM and Bmax=3.4±1.0 pmol mg−1 prot).

Among the 19 structural analogues of taurine, 6‐aminomethyl‐3‐methyl‐4H‐1,2,4‐benzothiadiazine 1,1‐dioxide (TAG), 2‐aminoethylarsonic (AEA), 2‐hydroxyethanesulfonic (ISE) and (±)cis‐2‐aminocyclohexane sulfonic acids (CAHS) displaced [3H]taurine binding (Ki=0.13, 0.13, 13.5 and 4.0 μM, respectively). These analogues did not interact with GABAA and GABAB receptors and did not affect taurine‐ and GABA‐uptake systems and GABA‐transaminase activity.

3‐Aminopropanesulfonic acid (OMO), β‐alanine, pyridine‐3‐sulfonic acid, N,N,N‐trimethyltaurine (TMT), 2‐(guanidino)ethanesulfonic acid (GES), ethanolamine‐O‐sulphate, N,N‐dimethyltaurine (DMT), taurine and (±)piperidine‐3‐sulfonic acid (PSA) inhibited [3H]muscimol binding to GABAA receptors with different affinities (Ki=0.013, 7.9, 24.6, 47.5, 52.0, 91.0, 47.5, 118.1 and 166.3 μM, respectively). Taurine, 2‐aminoethylphosphonic acid, DMT, TMT and OMO inhibited the binding of [3H]GABA to GABAB receptors with Ki's in the μM range (0.8, 3.5, 4.4, 11.3 and 5.0, respectively). GES inhibited taurine uptake (IC50=3.72 μM) and PSA GABA transaminase activity (IC50=103.0 μM).

In conclusion, AEA, TAG, ISE and CAHS fulfill the criteria for taurinergic agents.

British Journal of Pharmacology (2003) 138, 1163–1171. doi:10.1038/sj.bjp.0705134
Investigation of postjunctional α1‐ and α2‐adrenoceptor subtypes in vas deferens from wild‐type and α2A/D‐adrenoceptor knockout mice
Authors: Cleary Linda , Vandeputte Catherine , Docherty James R
Published: April 2003

The subtypes of α1‐ and α2‐adrenoceptor mediating contractions of vas deferens have been examined in wild‐type and α2A/D‐adrenoceptor knockout mice.

Maximum contractions to noradrenaline but not phenylephrine were significantly greater in vas from wild‐type. The α1A‐adrenoceptor antagonist RS100329 (5‐methyl‐3‐[3‐[4‐[2‐(2,2,2,‐trifluoroethoxy)phenyl]‐1‐piperazinyl]propyl]‐2,4‐(1H)‐pyrimidinedione) (10 nM) significantly shifted the potency of noradrenaline. The α2D‐adrenoceptor antagonist BRL 44408 (2‐[(4,5‐dihydro‐1H‐imidazol‐2‐yl)methyl]‐2,3‐dihydro‐1‐methyl‐1H‐isoindole) significantly reduced the maximum contraction to noradrenaline in wild‐type but not in knockout.

Following prazosin (0.1 μM), a component of the contraction to noradrenaline in wild‐type but not in knockout was sensitive to the α2‐adrenoceptor antagonist yohimbine.

Nifedipine (10 μM) or suramin (100 μM) reduced the contraction to 10 Hz stimulation for 4 s to an early peak and small maintained response. The peak was abolished by the α1‐adrenoceptor antagonist prazosin.

RS100329 or prazosin inhibited 10 Hz stimulation evoked contractions with a U‐shaped concentration‐response curve: inhibiting responses up to 0.1 μM, with a reversal of inhibition above this concentration. In the presence of suramin or nifedipine, the reversal of inhibition by high concentrations of prazosin was reduced.

The α1D‐adrenoceptor selective antagonist BMY7378 (8‐[2‐(4‐(2‐ methoxyphenyl)piperazin‐1‐yl)ethyl]‐8‐azaspiro[4,5]decane‐7,9‐dione) produced inhibition of 10 Hz evoked contractions only in high concentrations.

In conclusion, contractions to nerve stimulation in mouse vas deferens involve largely α1A‐adrenoceptors and purinoceptors. α1‐Adrenoceptor antagonists in high concentrations increase the purinergic response presumably by blocking prejunctional α2‐adrenoceptor‐mediated inhibition. In the presence of nifedipine, responses are predominantly α1‐adrenoceptor mediated. Contractions to exogenous noradrenaline involved both α1A‐ and α2A/D‐adrenoceptors in wild‐type mice.

British Journal of Pharmacology (2003) 138, 1069–1076. doi:10.1038/sj.bjp.138-0705137
In vivo antioxidant treatment protects against bleomycin‐induced lung damage in rats
Authors: Serrano‐Mollar A , Closa D , Prats N , Blesa S , Martinez‐Losa M , Cortijo J , Estrela J M , Morcillo E J , Bulbena O
Published: April 2003

This study examines the activity of the antioxidant N‐acetylcysteine on bleomycin‐induced pulmonary fibrosis in rats with emphasis on the early inflammatory phase.

Rats receiving N‐acetylcysteine (300 mg kg−1 day−1, intraperitoneal) had less augmented lung wet weight, and lower levels of proteins, lactate dehydrogenase, neutrophil and macrophage counts in bronchoalveolar lavage fluid and lung myeloperoxidase activity with a betterment of histological score at 3 days postbleomycin.

A diminished lung GSH/GSSG ratio and augmented lipid hydroperoxides were observed 3 days postbleomycin. These changes were attenuated by N‐acetylcysteine. Alveolar macrophages from bleomycin‐exposed rats released augmented amounts of superoxide anion and nitric oxide. N‐Acetylcysteine did not modify superoxide anion generation but reduced the increased production of nitric oxide.

N‐Acetylcysteine suppressed the bleomycin‐induced increased activation of lung NF‐κB (shift assay and immunohistochemistry), and decreased the augmented levels of the early inflammatory cytokines, tumour necrosis factor‐α, interleukin‐β, interleukin‐6 and macrophage inflammatory protein‐2 observed in bronchoalveolar lavage fluid at 1 and 3 days postbleomycin exposure.

At 15 days postbleomycin, N‐acetylcysteine decreased collagen deposition in bleomycin‐exposed rats (hydroxyproline content: 6351±669 and 4626±288 μg per lung in drug vehicle‐ and N‐acetylcysteine‐treated rats, respectively; P<0.05). Semiquantitative histological assessment at this stage showed less collagen deposition in N‐acetylcysteine‐treated rats compared to those receiving bleomycin alone.

These results indicate that N‐acetylcysteine reduces the primary inflammatory events, thus preventing cellular damage and the subsequent development of pulmonary fibrosis in the bleomycin rat model.

British Journal of Pharmacology (2003) 138, 1037–1048. doi:10.1038/sj.bjp.138-0705138
h5‐HT1B receptor‐mediated constitutive Gαi3‐protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5‐HT
Authors: Newman‐Tancredi Adrian , Cussac Didier , Marini Laetitia , Touzard Manuelle , Millan Mark J
Published: April 2003

Serotonin 5‐HT1B receptors couple to G‐proteins of the Gi/o family. However, their activation of specific G‐protein subtypes is poorly characterised. Using an innovative antibody capture/guanosine‐5′‐0‐(3‐[35S]thio)‐triphosphate ([35S]GTPγS) binding strategy, we characterised Gαi3 subunit activation by h5‐HT1B receptors stably expressed in Chinese hamster ovary (CHO) cells.

The agonists, 5‐HT, alniditan and BMS181,101, stimulated Gαi3, whereas methiothepin and SB224,289 behaved as inverse agonists. The selective 5‐HT1B receptor ligand, S18127, modestly stimulated Gαi3 and reversed the actions of both 5‐HT and methiothepin. S18127 (1 μM) also produced parallel, dextral shifts of the 5‐HT and methiothepin isotherms.

Isotopic dilution experiments ([35S]GTPγS versus GTPγS) revealed high‐affinity [35S]GTPγS binding to Gαi3 subunits in the absence of receptor ligands indicating constitutive activity. High‐affinity [35S]GTPγS binding was increased 2.8‐fold by 5‐HT with an increase in the affinity of GTPγS for Gαi3 subunits. In contrast, methiothepin halved the number of high‐affinity binding sites and decreased their affinity.

h5‐HT1B receptor‐mediated Gαi3 subunit activation was dependent on the concentration of NaCl. At 300 mM, 5‐HT stimulated [35S]GTPγS binding, basal Gαi3 activation was low and methiothepin was inactive. In contrast, at 10 mM NaCl, basal activity was enhanced and the inverse agonist activity of methiothepin was accentuated. Under these conditions, 5‐HT decreased Gαi3 activation.

In conclusion, at h5‐HT1B receptors expressed in CHO cells: (i) inverse agonist induced inhibition of Gαi3, and its reversal by S18127, reveals constitutive activation of this Gα subunit; (ii) constitutive Gαi3 activation can be quantified by isotopic dilution [35S]GTPγS binding and (iii) decreasing NaCl concentrations enhances Gαi3 activation and leads to protean agonist properties of 5‐HT: that is a switch to inhibition of Gαi3.

British Journal of Pharmacology (2003) 138, 1077–1084. doi:10.1038/sj.bjp.0705140
Activation of a glycine transporter on spinal cord neurons causes enhanced glutamate release in a mouse model of amyotrophic lateral sclerosis
Authors: Raiteri Luca , Paolucci Egle , Prisco Simona , Raiteri Maurizio , Bonanno Giambattista
Published: April 2003

The release of [3H]D‐aspartate ([3H]D‐ASP) or [3H]GABA evoked by glycine from spinal cord synaptosomes was compared in mice expressing mutant human SOD1 with a Gly93 Ala substitution ([SOD1‐G93A(+)]), a transgenic model of amyotrophic lateral sclerosis, and in control mice. Mice expressing mutated SOD1 were killed at the advanced phase of the pathology, when they showed signs of ingestion disability, because of paralysis of the posterior limbs. In control mice glycine concentration‐dependently evoked [3H]D‐ASP and [3H]GABA release. Potentiation of the spontaneous release of both amino acids is likely to be mediated by activation of a glycine transporter, since the effects of glycine were counteracted by the glycine transporter blocker glycyldodecylamide but not by the glycine receptor antagonists strychnine and 5,7‐dichlorokynurenate. The glycine‐evoked release of [3H]D‐ASP, but not that of [3H]GABA, was significantly more pronounced in SOD1‐G93A(+) than in control animals.

British Journal of Pharmacology (2003) 138, 1021–1025. doi:10.1038/sj.bjp.0705142
Differential effects of ascorbate on endothelium‐derived hyperpolarizing factor (EDHF)‐mediated vasodilatation in the bovine ciliary vascular bed and coronary artery
Authors: McNeish Alister J , Nelli Silvia , Wilson William S , Dowell Fiona J , Martin William
Published: April 2003

The ability of ascorbate to inhibit endothelium‐derived hyperpolarizing factor (EDHF)‐mediated vasodilatation was compared in the bovine perfused ciliary vascular bed and isolated rings of coronary artery.

Acetylcholine‐induced, EDHF‐mediated vasodilatation of the ciliary circulation was blocked following inclusion of ascorbate (50 μM, 120 min) in the perfusion fluid. The blockade was highly selective since ascorbate had no effect on the vasodilator actions of the KATP channel opener, levcromakalim, nor on the tonic vasodepressor action of basally released nitric oxide.

The possibility that concentration of ascorbate by the ciliary body was a prerequisite for blockade to occur was ruled out, since EDHF was still blocked when the anterior and posterior chambers were continuously flushed with Krebs solution or when both the aqueous and vitreous humour were drained.

Ascorbate at 50 μM failed to affect bradykinin‐ or acetylcholine‐induced, EDHF‐mediated vasodilatation in rings of bovine coronary artery. Raising the concentration to 3 mM did produce blockade of EDHF, but this was nonselective, since vasodilator responses to endothelium‐derived nitric oxide were also inhibited.

Thus, ascorbate (50 μM) is not a universal blocker of EDHF. Whether its ability to block in the bovine ciliary circulation, but not in the coronary artery, is due to differences in the nature of EDHF at the two sites, differences in vessel size (resistance arterioles versus conduit artery), the presence or absence of flow, or to some other factor remains to be determined.

British Journal of Pharmacology (2003) 138, 1172–1180. doi:10.1038/sj.bjp.0705143
Mechanisms of hydrogen‐peroxide‐induced biphasic response in rat mesenteric artery
Authors: Gao Yu‐Jing , Hirota Simon , Zhang Da‐Wei , Janssen Luke J , Lee Robert M K W
Published: April 2003

In phenylephrine (PHE) (1 μM)‐precontracted superior mesenteric arteries from adult rats, low concentration of hydrogen peroxide (H2O2, 10–100 μM) caused only contraction, while high concentration of H2O2 (0.3–1 mM) caused a biphasic response: a transient contraction followed by a relaxation response.

Endothelium removal did not affect the biphasic response. 7,7‐Dimethyl‐(5Z,8Z)‐eicosadienoic acid, diclofenac, furegrelate, or SQ 29548 greatly inhibited the contraction but did not affect the relaxation. 17‐Octadecynoic acid, eicosatriynoic acid, ICI 198615, SQ 22536, or ODQ did not inhibit the biphasic response.

KCl at 40 mM inhibited the relaxation response to H2O2 by 98±24%. 4‐Aminopyridine (4‐AP) inhibited while tetraethylammonium chloride (TEA), charybdotoxin, or glibenclamide attenuated the relaxation response. A combination of 4‐AP, TEA and glibenclamide mimicked the effects of 40 mM KCl. Iberiotoxin, apamin, or barium chloride did not inhibit the relaxation response.

H2O2 at 1 mM hyperpolarized membrane potential and reversibly augmented K+ current in smooth muscle cells of mesenteric artery. These effects of H2O2 were attenuated significantly by 4‐AP.

In summary, in PHE‐precontracted rat mesenteric artery: (1) the response to H2O2 shifted qualitatively from contraction to a biphasic response as H2O2 increased to 0.3 mM or higher; (2) the relaxation response is caused by the activation of K+ channels, with voltage‐dependent K+ channels playing a primary role; and the contraction is likely to be mediated by thromboxane A2; (3) the K+ channel activation by H2O2 is independent of phospholipase A2, cyclooxygenase, lipoxygenase, cytochrome P450 monooxygenase, adenylate or guanylate cyclase.

British Journal of Pharmacology (2003) 138, 1085–1092. doi:10.1038/sj.bjp.0705147
Structural requirements for novel willardiine derivatives acting as AMPA and kainate receptor antagonists
Authors: More Julia C A , Troop Helen M , Dolman Nigel P , Jane David E
Published: April 2003

The natural product willardiine is an AMPA receptor agonist. We have examined the structural changes required to convert willardiine into an antagonist at AMPA and kainate receptors. Structure–activity analysis has been carried out to discover the structural features required to increase the potency and/or selectivity of the antagonists at AMPA or kainate receptors.

Reduction of the fast component of the dorsal root‐evoked ventral root potential (fDR‐VRP) has been used to investigate AMPA receptor antagonist activity. To examine antagonist activity at kainate receptors, the ability of compounds to depress kainate‐induced depolarisations of dorsal root fibres was assessed.

Blocking ionisation of the uracil ring by adding a methyl group to the N3 position was not sufficient to convert willardiine into an antagonist. However, willardiine derivatives with a side‐chain bearing a carboxylic acid group at the N3‐position of the uracil ring could antagonise AMPA and kainate receptors.

S stereochemistry was optimal for antagonism. When compounds with differing interacidic group chain lengths were compared, a group chain length of two methylene groups was preferable for AMPA receptor antagonism in the series of compounds bearing a carboxyalkyl side chain (UBP275, UBP277 and UBP279 reduced the fDR‐VRP with IC50 values of 287±41, 23.8±3.9 and 136±17 μM, respectively). For kainate receptor antagonism, two or three methylene groups were almost equally acceptable (UBP277 and UBP279 reduced dorsal root kainate responses with apparent KD values of 73.1±4.5 and 60.5±4.1 μM, respectively).

Adding an iodo group to the 5‐position of UBP277 and UBP282 enhanced activity at kainate receptors (UBP291 and UBP301 antagonised kainate responses on the dorsal root with apparent KD values of 9.83±1.62 and 5.94±0.63 μM, respectively).

The most useful antagonist identified in this study was UBP301, which was a potent and ∼30‐fold selective kainate receptor antagonist. UBP282 may also be of use in isolating a non‐GluR5‐mediated kainate response.

British Journal of Pharmacology (2003) 138, 1093–1100. doi:10.1038/sj.bjp.0705148
Oral nicorandil recaptures the waned protection from preconditioning in vivo
Authors: Iliodromitis Efstathios K , Cokkinos Philip , Zoga Anastasia , Steliou Ioulia , Vrettou Agathi R , Kremastinos Dimitrios Th
Published: April 2003

Protection from preconditioning (PC) wanes and is eventually lost when multiple bouts of short ischemia or a prolonged reperfusion interval precedes the following sustained ischemia. The activation of mitochondrial KATP channels plays a pivotal role in the intracellular signaling of PC. We tested whether the KATP channel opener nicorandil (nic) preserves the given protection from PC in conditions where this benefit decays and is lost.

Eight groups of rabbits were divided into two equal series of experiments, one without nic (placebo) and one with nic treatment. Nic was given orally for 5 consecutive days in a dose of 5 mg kg−1 d−1. In a second step, four additional groups were treated with nic plus the KATP channel blocker 5HD and 1 additional control group with nitroglycerin only. All the animals were anesthetized and then subjected to 30 min of myocardial ischemia and 2 h of reperfusion with one of the following interventions before the sustained ischemia: Control groups to no intervention; 3PC groups to three cycles of 5‐min ischemia–10‐min reperfusion; 8PC groups to eight cycles of 5‐min ischemia – 10‐min reperfusion; and 3PC90 groups to the same interventions as the 3PC groups but with a prolonged (90 min) intervening reperfusion interval before the sustained ischemia. The infarcted and the risk areas were expressed in percent.

There was no significant change in infarct size between the placebo, the nic and the 5HD‐nic in the control groups (41.5±4.7, 43.9±7.1 and 48.7±6.4%) and 3PC groups (10.3±3.4, 12.2±3.9 and 12.6±4.5%). However, there was a significant decrease after nic treatment in groups 8PC (47.7±8.8% vs 13.0±2.6%, P<0.01) and 3PC90 (37.3±6.0% vs 14.2±2.4%, P<0.01), which was abrogated (38.2±4.7 and 42.7±4.4%, respectively, for 8PC and 3PC90 groups). Nitroglycerin had no effect on infarct size (39.1±3.1%, P=NS vs other controls).

Oral treatment with nic recaptures the waned protection of PC, both after repetitive bouts of short ischemia or after a prolonged reperfusion interval, preserving the initially obtained benefit. Nic by itself is insufficient to initiate PC in vivo.

British Journal of Pharmacology (2003) 138, 1101–1106. doi:10.1038/sj.bjp.0705149
Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB‐1893 and MPEP
Authors: Mathiesen Jesper Mosolff , Svendsen Nannette , Bräuner‐Osborne Hans , Thomsen Christian , Ramirez M Teresa
Published: April 2003

We have identified 2‐methyl‐6‐(2‐phenylethenyl)pyridine (SIB‐1893) and 2‐methyl‐6‐phenylethynyl pyridine hydrochloride (MPEP) as positive allosteric modulators for the hmGluR4. SIB‐1893 and MPEP enhanced the potency and efficacy of L‐2‐amino‐4‐phophonobutyrate (L‐AP4) in guanosine 5′‐O‐(3‐[35S]thiotriphosphate ([35S]GTPγS) binding and efficacy in cAMP studies. These effects were fully blocked by the mGluR4 competitive antagonist (RS)‐α‐cyclopropyl‐4‐phosphonophenylglycine (CPPG), indicating a dependency on receptor activation. Although SIB‐1893 and MPEP had no effects alone in GTPγS binding, effects were observed in the cell‐based cAMP assay due to media‐derived activation as indicated by CPPG inhibition. Positive modulation of the mGluR4 was a receptor‐specific effect since SIB‐1893 and MPEP had neither effects on mGluR2‐expressing cells nor on the parent BHK cell line. In [3H]L‐AP4 binding, a two‐fold decrease in KD but not in Bmax was observed with 100 μM SIB‐1893, whereas MPEP affected neither parameter. Finally, SIB‐1893 and MPEP failed to displace [3H]L‐AP4 binding. Taken together, these data identify positive allosteric modulators for the hmGluR4.

British Journal of Pharmacology (2003) 138, 1026–1030. doi:10.1038/sj.bjp.0705159
Erythropoietin fosters both intrinsic and extrinsic neuronal protection through modulation of microglia, Akt1, Bad, and caspase‐mediated pathways
Authors: Chong Zhao Zhong , Kang Jing‐Qiong , Maiese Kenneth
Published: April 2003

Erythropoietin (EPO) plays a significant role in the hematopoietic system, but the function of EPO as a neuroprotectant and anti‐inflammatory mediator requires further definition. We therefore examined the cellular mechanisms that mediate protection by EPO during free radical injury in primary neurons and cerebral microglia.

Neuronal injury was evaluated by trypan blue, DNA fragmentation, phosphatidylserine (PS) exposure, Akt1 phosphorylation, Bad phosphorylation, mitochondrial membrane potential, and cysteine protease activity. Microglial activation was assessed through proliferating cell nuclear antigen and PS receptor expression.

EPO provides intrinsic neuronal protection that is both necessary and sufficient to prevent acute genomic DNA destruction and subsequent membrane PS exposure, since protection by EPO is completely abolished by cotreatment with an anti‐EPO neutralizing antibody.

Extrinsic protection by EPO is offered through the inhibition of cerebral microglial activation and the suppression of microglial PS receptor expression for the prevention of neuronal phagocytosis. In regards to microglial chemotaxis, EPO modulates neuronal poptotic membrane PS exposure necessary for microglial activation primarily through the regulation of caspase 1.

EPO increases Akt1 activity, phosphorylates Bad, and maintains neuronal nuclear DNA integrity through the downstream modulation of mitochrondrial membrane potential, cytochrome c release, and caspase 1, 3, and 8‐like activities.

Elucidating the intrinsic and extrinsic protective pathways of EPO that mediate both neuronal integrity and inflammatory microglial activation may enhance the development of future therapies directed against acute neuronal injury.

British Journal of Pharmacology (2003) 138, 1107–1118. doi:10.1038/sj.bjp.0705161