bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding and effect of KATP channel openers in the absence of Mg2+
Authors: Russ Ulrich , Lange Ulf , Löffler‐Walz Cornelia , Hambrock Annette , Quast Ulrich 
Published: May 2003

Openers of ATP‐sensitive K+ channels (KATP channels) are thought to act by enhancing the ATPase activity of sulphonylurea receptors (SURs), the regulatory channel subunits. At higher concentrations, some openers activate KATP channels also in the absence of MgATP. Here, we describe binding and effect of structurally diverse openers in the absence of Mg2+ and presence of EDTA.
Binding of openers to SUR2B was measured using a mutant with high affinity for [3H]glibenclamide ([3H]GBC). In the absence of Mg2+, ‘typical' openers (benzopyrans, cyanoguanidines and aprikalim) inhibited [3H]GBC binding with Ki values ∼200 × higher than in the presence of MgATP. Minoxidil sulphate and nicorandil were inactive, whereas binding of diazoxide was unaffected by MgATP.
In the absence/presence of MgATP, N‐cyano‐N′‐(1,1‐dimethylpropyl)‐N″‐3‐pyridylguanidine (P1075) activated the Kir6.2/SUR2B channel in inside–out patches with EC50=2000/67nM and Emax=32/134%. In the absence of Mg2+, responses were variable with only a small part of the variability being explained by a decrease in channel responsiveness with time after patch excision and to differences in the ATP sensitivity between patches.
The rank order of efficacy of the openers was P1075>rilmakalim ∼nicorandil>diazoxide>minoxidil sulphate.
The data show that structurally diverse openers are able to bind to, and to activate the Kir6.2/SUR2B channel by a pathway independent of ATP hydrolysis. These effects are observed at concentrations used to define the biochemical mechanism of the openers in the presence of MgATP and allow the openers to be classified into ‘typical’ and ‘atypical’ KCOs with diazoxide standing apart.

British Journal of Pharmacology (2003) 139, 368–380. doi:10.1038/sj.bjp.0705238
Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid‐induced colitis
Authors: Ukil A , Maity S , Karmakar S , Datta N , Vedasiromoni J R , Das Pijush K 
Published: May 2003

Inflammmatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leucocyte infiltration and upregulation of proinflammatory cytokines. In this study, we have investigated the protective effects of curcumin, an anti‐inflammatory and antioxidant food derivative, on 2,4,6‐ trinitrobenzene sulphonic acid‐induced colitis in mice, a model for IBD.
Intestinal lesions (judged by macroscopic and histological score) were associated with neutrophil infiltration (measured as increase in myeloperoxidase activity in the mucosa), increased serine protease activity (may be involved in the degradation of colonic tissue) and high levels of malondialdehyde (an indicator of lipid peroxidation).
Dose–response studies revealed that pretreatment of mice with curcumin (50 mg kg−1 daily i.g. for 10 days) significantly ameliorated the appearance of diarrhoea and the disruption of colonic architecture. Higher doses (100 and 300 mg kg−1) had comparable effects.
In curcumin‐pretreated mice, there was a significant reduction in the degree of both neutrophil infiltration (measured as decrease in myeloperoxidase activity) and lipid peroxidation (measured as decrease in malondialdehyde activity) in the inflamed colon as well as decreased serine protease activity.
Curcumin also reduced the levels of nitric oxide (NO) and O2− associated with the favourable expression of Th1 and Th2 cytokines and inducible NO synthase. Consistent with these observations, nuclear factor‐κB activation in colonic mucosa was suppressed in the curcumin‐treated mice.
These findings suggest that curcumin or diferuloylmethane, a major component of the food flavour turmeric, exerts beneficial effects in experimental colitis and may, therefore, be useful in the treatment of IBD.

British Journal of Pharmacology (2003) 139, 209–218. doi:10.1038/sj.bjp.0705241
Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by α2‐adrenoceptors in the presence of experimental colitis
Authors: Blandizzi Corrado , Fornai Matteo , Colucci Rocchina , Baschiera Fabio , Barbara Giovanni , Giorgio Roberto De , Ponti Fabrizio De , Breschi Maria Cristina , Tacca Mario Del 
Published: May 2003

This study investigates the influence of intestinal inflammation on: (1) the control of intestinal neurotransmission and motility by prejunctional α2‐adrenoceptors and (2) the expression of intestinal α2‐adrenoceptors. Experimental colitis was induced by intrarectal administration of 2,4‐dinitrobenzenesulphonic acid (DNBS) to rats.
UK‐14,304 inhibited atropine‐sensitive electrically evoked contractions of ileal and colonic longitudinal muscle preparations. UK‐14,304 acted with similar potency, but higher efficacy, on tissues from DNBS‐treated animals; its effects were antagonized with greater potency by phentolamine than rauwolscine.
Electrically induced [3H]noradrenaline release from ileal preparations was reduced in the presence of colitis. Tritium outflow was decreased by UK‐14,304 and stimulated by rauwolscine or phentolamine: these effects were enhanced in preparations from animals with colitis.
Reverse transcription–polymerase chain reaction and Western blot assay demonstrated the protein expression of α2A‐adrenoceptors in mucosal and muscular tissues isolated from ileum and colon. The induction of colitis increased α2A‐adrenoceptor expression in both ileal and colonic muscular layers, without concomitant changes in mucosal tissues.
Induction of colitis reduced gastrointestinal propulsion of a charcoal suspension in vivo. In this setting, the gastrointestinal transit was inhibited by intraperitoneal (i.p.) UK‐14,304 and stimulated by i.p. rauwolscine. After pretreatment with guanethidine, the stimulant action of rauwolscine no longer occurred, and UK‐14,304 exerted a more prominent inhibitory effect that was antagonized by rauwolscine.
The present results indicate that, in the presence of intestinal inflammation, prejunctional α2‐adrenoceptors contribute to an enhanced inhibitory control of cholinergic and noradrenergic transmission both at inflamed and noninflamed distant sites. Evidence was obtained that such modulatory actions depend on an increased expression of α2A‐adrenoceptors within the enteric nervous system.

British Journal of Pharmacology (2003) 139, 309–320. doi:10.1038/sj.bjp.0705249
Mechanisms involved in the stimulation of prostacyclin synthesis by human lymphocytes in human umbilical vein endothelial cells
Authors: Merhi‐Soussi Faten , Dominguez Zury , Macovschi Olga , Dubois Madeleine , Nemoz Georges , Lagarde Michel , Prigent Annie‐France 
Published: May 2003

Endothelial cells play an important role in the modulation of vascular tone because of their ability to produce vasoactive substances such as prostacyclin (PGI2). Cell–cell contact between human umbilical vein endothelial cells (HUVEC) and peripheral blood lymphocytes has been shown to stimulate endothelial PGI2 synthesis by increasing free arachidonic acid availability through endothelial cytosolic phospholipase A2 (cPLA2) activation. In this study, we sought to determine whether phospholipase C (PLC) and D (PLD) activation also contributes, besides cPLA2, to the lymphocyte‐induced PGI2 synthesis in HUVEC, and to delineate further the potential mechanisms of cPLA2 activation triggered by the interaction of HUVEC with lymphocytes.
Pretreatment of endothelial cells with the PI‐PLC inhibitor U‐73122 before the coincubation with lymphocytes markedly inhibited the PGI2 output whereas the diacylglycerol (DAG) lipase inhibitor RHC 80267 and ethanol had no effect. These results suggest that PLC may be involved through inositol trisphosphate generation and calcium mobilization, and that neither DAG nor phosphatidic acid (PtdOH) was used as sources of arachidonic acid.
The stimulated PGI2 synthesis was protein kinase C (PKC)‐independent but strongly inhibited by the mitogen‐activated protein kinase kinase (MEK) inhibitors PD98059 and U‐0126 and by the Src kinase inhibitor PP1.
Immunoblot experiments showed an increased phosphorylation of the extracellular signal‐regulated kinases 1/2 (ERK1/2) upon lymphocyte addition till 4 h coincubation. Phosphorylation was markedly inhibited by U‐0126 and PP1 addition.
Collectively, these results suggest that the signaling cascade triggered by lymphocytes in endothelial cells involves an Src kinase/ERK1/2 pathway leading to endothelial cPLA2 activation.

British Journal of Pharmacology (2003) 139, 321–328. doi:10.1038/sj.bjp.0705253
Deletion of the UT receptor gene results in the selective loss of urotensin‐II contractile activity in aortae isolated from UT receptor knockout mice
Authors: Behm David J , Harrison Stephen M , Ao Zhaohui , Maniscalco Kristeen , Pickering Susan J , Grau Evelyn V , Woods Tina N , Coatney Robert W , Doe Christopher P A , Willette Robert N , Johns Douglas G , Douglas Stephen A 
Published: May 2003

Urotensin‐II (U‐II) is among the most potent mammalian vasoconstrictors identified and may play a role in the aetiology of essential hypertension. Currently, only one mouse U‐II receptor (UT) gene has been cloned. It is postulated that this protein is solely responsible for mediating U‐II‐induced vasoconstriction.
This hypothesis has been investigated in the present study, which assessed basal haemodynamics and vascular reactivity to hU‐II in wild‐type (UT(+/+)) and UT receptor knockout (UT(−/−)) mice.
Basal left ventricular end‐diastolic and end‐systolic volumes/pressures, stroke volumes, mean arterial blood pressures, heart rates, cardiac outputs and ejection fractions in UT(+/+) mice and in UT(−/−) mice were similar.
Relative to UT(+/+) mouse isolated thoracic aorta, where hU‐II was a potent spasmogen (pEC50=8.26±0.08) that evoked relatively little vasoconstriction (17±2% 60 mM KCl), vessels isolated from UT(−/−) mice did not respond to hU‐II. However, in contrast, the superior mesenteric artery isolated from both the genotypes did not contract in the presence of hU‐II. Reactivity to unrelated vasoconstrictors (phenylephrine, endothelin‐1, KCl) and endothelium‐dependent/independent vasodilator agents (carbachol, sodium nitroprusside) was similar in the aorta and superior mesenteric arteries isolated from both the genotypes.
The present study is the first to directly link hU‐II‐induced vasoconstriction with the UT receptor. Deletion of the UT receptor gene results in loss of hU‐II contractile action with no ‘nonspecific’ alterations in vascular reactivity. However, as might be predicted based on the limited contractile efficacy recorded in vitro, the contribution that hU‐II and its receptor make to basal systemic haemodynamics appears to be negligible in this species.

British Journal of Pharmacology (2003) 139, 464–472. doi:10.1038/sj.bjp.0705254
Dihydroergotamine and its metabolite, 8′‐hydroxy‐dihydroergo‐tamine, as 5‐HT1A receptor agonists in the rat brain
Authors: Hanoun N , Saurini F , Lanfumey L , Hamon M , Bourgoin S 
Published: May 2003

In addition to stopping migraine attacks, dihydroergotamine (DHE) is an efficient drug for migraine prophylaxis. Whether 5‐HT1A receptors could contribute to the latter action was assessed by investigating the effects of DHE and its metabolite, 8′‐OH‐DHE, on these receptors in the rat brain.
Membrane binding assays with [3H]8‐OH‐DPAT and [3H]WAY 100635 as radioligands showed that both DHE (IC50=28–30 nM) and 8′‐OH‐DHE (IC50=8–11 nM) are high‐affinity 5‐HT1A receptor ligands.
Both DHE and 8′‐OH‐DHE enhanced the specific binding of [35S]GTP‐γ‐S to the dorsal raphe nucleus and the hippocampus in brain sections, but to a lower extent than 5‐carboxamido‐tryptamine (5‐CT) in the latter area.
Both DHE (EC50=10.9±0.3 nM) and 8′‐OH‐DHE (EC50=30.4±0.8 nM) inhibited the firing of serotoninergic neurons in the dorsal raphe nucleus within brain stem slices.
Intracellular recording showed that 8′‐OH‐DHE was more potent than DHE to hyperpolarize CA1 pyramidal cells in rat hippocampal slices.
Both the stimulatory effects of DHE and 8′‐OH‐DHE on [35S]GTP‐γ‐S binding and their electrophysiological effects were completely prevented by the selective 5‐HT1A receptor antagonist WAY 100635.
As expected of 5‐HT1A receptor partial agonists, DHE and 8′‐OH‐DHE prevented any subsequent hyperpolarization of CA1 pyramidal cells by 5‐HT or 5‐CT.
Through their actions at 5‐HT1A auto‐ (in the dorsal raphe nucleus) and hetero‐(notably in the hippocampus) receptors, DHE, and even more its metabolite 8′‐OH‐DHE, can exert both an inhibitory influence on neuronal excitability and anxiolytic effects which might contribute to their antimigraine prophylactic efficiency.

British Journal of Pharmacology (2003) 139, 424–434. doi:10.1038/sj.bjp.0705258
Cellular actions of opioids on periaqueductal grey neurons from C57B16/J mice and mutant mice lacking MOR‐1
Authors: Vaughan Christopher W , Bagley Elena E , Drew Geoffrey M , Schuller Alwin , Pintar John E , Hack Stephen P , Christie MacDonald J 
Published: May 2003

Patch clamp recordings were made from periaqueductal grey (PAG) neurons in vitro to investigate the cellular actions of opioids in wild‐type C57B16/J mice and mutant mice lacking the first exon of the μ‐opioid (MOP) receptor.
In wild‐type mice, the κ‐(KOP) agonist U‐69593 (300 nM) and the mixed μ/δ‐opioid agonist met‐enkephalin (10 μM), but not the δ‐(DOP) agonist deltorphin (300 nM), reduced the amplitude of evoked GABAA‐mediated inhibitory postsynaptic currents (IPSCs). Met‐enkephalin and U‐69593 also reduced the rate of spontaneous miniature IPSCs, but had no effect on their amplitude and kinetics. In μ‐receptor‐deleted mice, only U‐69593 (300 nM) reduced the amplitude of evoked IPSCs.
In wild‐type mice, the MOP agonist DAMGO (3 μM) produced an outward current in 76% of the neurons. Deltorphin and U‐69593 produced outward currents in 24 and 32% of the neurons, respectively. In μ‐receptor‐deleted mice, deltorphin and U‐69593 produced similar outward currents in 32 and 27% of the neurons, respectively, while DAMGO was without effect. All neurons in both the wild‐type and μ‐receptor‐deleted mice responded with similar outward currents to either the GABAB receptor agonist baclofen (10 μM), or the opioid‐like receptor ORL1 (NOP) agonist nociceptin (300 nM).
The DAMGO‐, deltorphin‐, U‐69593‐, baclofen‐ and nociceptin‐induced currents displayed inward rectification and reversed polarity at −109 to −116 mV.
These findings indicate that μ‐, δ‐ and κ‐opioid receptor activation has complex pre‐ and postsynaptic actions within the mouse PAG. This differs to the rat PAG where only μ‐opioid receptor actions have been observed.

British Journal of Pharmacology (2003) 139, 362–367. doi:10.1038/sj.bjp.0705261
Receptor signaling mechanisms underlying muscarinic agonist‐evoked contraction in guinea‐pig ileal longitudinal smooth muscle
Authors: Unno T , Kwon S‐C , Okamoto H , Irie Y , Kato Y , Matsuyama H , Komori S 
Published: May 2003

In guinea‐pig ileal longitudinal muscle, muscarinic partial agonists, 4‐(N‐[3‐chlorophenyl]‐carbomoyloxy)‐2‐butynyl‐trimethylammonium (McN‐A343) and pilocarpine, each produced parallel increases in tension and cytosolic Ca2+ concentration ([Ca2+]c) with a higher EC50 than that of the full agonist carbachol. The maximum response of [Ca2+]c or tension was not much different among the three agonists. The Ca2+ channel blocker nicardipine markedly inhibited the effects of all three agonists
The contractile response to any agonist was antagonized in a competitive manner by M2 receptor selective antagonists (N,N′‐bis[6‐[[(2‐methoyphenyl)methyl]amino]hexyl]‐1,8‐octanediamine tetrahydrochloride and 11‐[[2‐[(diethlamino)methyl]‐1‐piperidinyl]acetyl]‐5,11‐dihydro‐6H‐pyrido[2,3‐b][1,4] benzodiazepine‐6‐one), and the apparent order of M2 antagonist sensitivity was McN‐A343>pilocarpine>carbachol. M3 receptor selective antagonists, 1,1‐dimethyl‐4‐diphenylacetoxypiperidinium iodide and darifenacin, both severely depressed the maximum response for McN‐A343, while darifenacin had a similar action in the case of pilocarpine. Both M3 antagonists behaved in a competitive manner in the case of the carbachol response.
McN‐A343 failed to release Ca2+ from the intracellular stores, and the Ca2+‐releasing action of pilocarpine was very weak compared with that of carbachol. All three agonists were capable of increasing Ca2+ sensitivity of the contractile proteins.
McN‐A343 rarely produced membrane depolarization, but always accelerated electrical spike discharge. Pilocarpine effect was more often accompanied by membrane depolarization, as was usually seen using carbachol.
The results suggest that muscarinic agonist‐evoked contractions result primarily from the integration of Ca2+ entry associated with the increased spike discharge and myofilaments Ca2+ sensitization, and that Ca2+ store release may contribute to the contraction indirectly via potentiation of the electrical membrane responses. They may also support the idea that an interaction of M2 and M3 receptors plays a crucial role in mediating the contraction response.

British Journal of Pharmacology (2003) 139, 337–350. doi:10.1038/sj.bjp.0705267
Consequences of removing a keystone herbivore for the abundance and diversity of arthropods associated with a cruciferous shrub
Authors: González‐Megías Adela , Gómez José M. 
Published: May 2003

Abstract. 1. The effect of the removal of Timarcha lugens (Chrysomelidae), one of the main herbivores of Hormathophylla spinosa (Cruciferae), on the abundance of co‐occurring phytophagous insects, the abundance of non‐phytophagous arthropods (detritivores, predators, and parasitoids), and the structure and diversity of the entire arthropod community, was studied for 3 years (1999–2001).2. There was competition between T. lugens and co‐occurring herbivores; the removal of T. lugens was correlated with an increase in the abundance of sap‐suckers, flower‐feeders, and, above all, folivores.3. Timarcha lugens also had an indirect effect on arthropods belonging to other trophic levels; the abundance of predators increased significantly after the removal of T. lugens.4. Community composition was affected by the experimental removal. In addition, the diversity of the overall community increased after removal of T. lugens.5. The study demonstrated experimentally that T. lugens has a significant effect not only on other species belonging to the same trophic level, but also on the abundance of species belonging to higher trophic levels, and, consequently, on the entire structure and diversity of the complex community in which it is immersed.
Dispersal between host populations in field conditions: navigation rules in the parasitoid Venturia canescens
Authors: Desouhant E. , Driessen G. , Lapchin L. , Wielaard S. , Bernstein C. 
Published: May 2003

Abstract. 1. Dispersal is a life‐history trait that can have great ecological and evolutionary consequences, however understanding of how insects disperse is limited.2. Navigation rules of the solitary koinobiont parasitoid of the pyralid moth larvae Venturia canescens (Gravenhorst) were studied in conditions that it is likely to meet when dispersing between host populations and in the absence of cues related directly to the presence of hosts.3. Mark–release–recapture experiments were conducted in a natural host‐free habitat, and letting the animals disperse for different periods.4. In the presence of vegetation, wasps seemed to disperse rapidly (1 h for an area of ≥ 1 ha) and capture rates were independent of both dispersal time and distance from the release point.5. The navigation rules of V. canescens during dispersal between tree stands can be summarised as: move up‐ or down‐wind, avoid or pass through open, sunny areas, and go for shady and dense vegetation.6. The consequences of the navigation rules for host–parasitoid dynamics are discussed in relation to different spatial scales.
The use of field–based social information in eusocial foragers: local enhancement among nestmates and heterospecifics in stingless bees
Authors: Slaa E. Judith , Wassenberg Jacoba , Biesmeijer Jacobus C. 
Published: May 2003

Abstract. 1. Foragers of social insects can be guided to profitable food sources by social information transfer within the nest. This study showed that in addition to such an information‐centre strategy, social information in the field also plays an important role in individual foraging decisions. The effect of the presence of a nestmate on individual decision‐making on where to forage was investigated in six species of stingless bee that differ in their recruitment system. Some species preferred to feed close to a nestmate (local enhancement) whereas other species actively avoided landing close to a nestmate. The term local inhibition is introduced for this avoidance behaviour.2. Local enhancement and local inhibition were species specific but were not related to the species' recruitment system.3. Local enhancement and local inhibition were affected by the individual's experience with the food source. Newly recruited foragers of Trigona amalthea showed local enhancement whereas experienced foragers showed local inhibition.4. These individual decision‐making rules explained accurately the spatial distribution of recruited nestmates: foraging groups of T. amalthea, which shows local inhibition, were more dispersed than foraging groups of Oxytrigona mellicolor, which shows local enhancement.5. The effect of heterospecifics on stingless bee flower choice was investigated for 18 species combinations. Landing decisions were influenced significantly by the aggressiveness and the body size of the resident bee. Larger and more aggressive heterospecifics were avoided, whereas in some cases less aggressive bees acted as an attraction cue.
Temporal priority and intra‐guild predation in temporary waters: an experimental study using Namibian desert dragonflies
Authors: Padeffke Tanja , Suhling Frank 
Published: May 2003

Abstract. 1. Intra‐guild predation between early larval instars of two co‐existing dragonflies, Sympetrum fonscolombii and Trithemis kirbyi, was investigated with respect to temporal advantage and growth. Three situations were simulated experimentally: (1) Sympetrum fonscolombii began development 11 days before T. kirbyi. (2) Trithemis kirbyi began development 11 days before S. fonscolombii. (3) Both species began on the same day.2. With a temporal advantage of 11 days to the second species, the resulting larval density of the respective first species was significantly higher than that of the second species.3. Without a temporal advantage, the survival of S. fonscolombii was higher than that of T. kirbyi, and S. fonscolombii had a larger size due to faster growth than T. kirbyi. Hence, it is assumed that survival depended on early oviposition as well as on larval growth.4. To test the relevance of the laboratory results, observations at artificial ponds in the Namibian semi‐desert were conducted. Trithemis kirbyi was the first species colonising these ponds while S. fonscolombii arrived 15 days later. In field samples, many more Trithemis larvae than Sympetrum larvae were found, a pattern similar to the laboratory experiments in which T. kirbyi enjoyed a temporal advantage.