bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha‐1 adrenoceptors: evaluation of receptor subtype‐binding kinetics in intact arterial tissues and comparison with membrane binding
Authors: Tanaka Takashi , Zhang Li , Suzuki Fumiko , Muramatsu Ikunobu 
Published: February 2004

The binding kinetics of [3H]‐prazosin were measured using intact segments of rat tail artery (RTA) and thoracic aorta (RAO), and the data were compared with those obtained using a conventional membrane ligand‐binding method.
In intact RTA and RAO segments, [3H]‐prazosin bound reversibly in a time‐dependent and receptor‐specific manner at 4°C to alpha‐1 adrenoceptors (ARs) of the plasma membrane, with affinities (pKD: 9.5 in RTA; 9.9 in RAO) that were in agreement with values estimated by a conventional membrane ligand‐binding method. However, nonspecific binding was considerably higher in RAO than RTA, failing to detect clearly the specific binding at high concentrations (>300 pM) of [3H]‐prazosin in binding experiments with RAO segments and membranes.
The abundance of receptor in the RTA and RAO (Bmax mg−1 of total tissue protein), estimated using the tissue segment‐binding approach (527±14 fmol mg−1 for RTA; 138±4 fmol mg−1 for RAO), was about 25‐fold higher than values estimated using a conventional membrane‐binding method (22±5 fmol mg−1 for RTA; 5±1 fmol mg−1 for RAO).
Binding competition experiments using intact tissue segments or membranes derived from RTA tissue yielded comparable data, indicating a coexistence of alpha‐1A AR (high affinity for prazosin, KMD‐3213 and WB4101 and low affinity for BMY 7378) and alpha‐1B AR (high affinity for prazosin but low affinity for KMD‐3213, WB4101 and BMY 7378).
In RAO tissue, careful evaluation of the tissue segment‐binding assay revealed the coexpression of alpha‐1B AR (high affinity for prazosin, but low affinity for KMD‐3213 and BMY 7378) and alpha‐1D AR (high affinity for prazosin and BMY 7378, but low affinity for KMD‐3213), whereas the membrane‐binding approach failed to detect these receptor subtypes with certainty.
The present study indicates that previous estimates of alpha‐1 AR density and alpha‐1 AR subtypes obtained by a conventional membrane‐binding approach, as opposed to our improved tissue segment‐binding assay, may have substantially underestimated the abundance of receptors present in arterial tissues, and may have failed to identify accurately the presence of receptor subtypes. Advantages and disadvantages of the tissue segment‐binding approach are discussed.

British Journal of Pharmacology (2004) 141, 468–476. doi:10.1038/sj.bjp.0705627
5‐Hydroxytryptamine is biotransformed by CYP2C9, 2C19 and 2B6 to hydroxylamine, which is converted into nitric oxide
Authors: Fradette Caroline , Yamaguchi Nobuharu , Du Souich Patrick 
Published: February 2004

There is circumstantial evidence suggesting that 5‐hydroxytryptamine (5‐HT) could be biotransformed by enzymatic systems other than monoamino oxidase A, and that the isoforms of cytochrome P450 may be a source of nitric oxide. This study aimed to assess whether cytochrome P450 contributes to 5‐HT biotransformation, and to provide evidence that 5‐HT metabolism generates nitric oxide.
Addition of 5‐HT to cultured hepatocytes yielded 5‐hydroxyindol acetic acid, a formation modulated by cytochrome P450 enzyme inducers and inhibitors. Recombinant human CYP2B6, 2C9 and 2C19 biotransformed 5‐HT in 5‐hydroxyindol acetic acid, but not CYP1A2, 2D6 or 3A4.
Cultured hepatocytes with 5‐HT generated nitric oxide, the amount of which was altered by cytochrome P450 enzyme inducers and inhibitors. In the presence of CYP2B6, 2C9 and 2C19, 5‐HT relaxed precontracted isolated aortic rings, with or without endothelium, an effect prevented by the addition of methylene blue and an inhibitor of catalase, but not by myoglobin. In the absence of catalase, hydroxylamine was always assayed as a byproduct of 5‐HT metabolism.
In conclusion, CYP2B6, 2C9 and 2C19 biotransform 5‐HT, yielding hydroxylamine, which is converted to nitric oxide in the presence of catalase.

British Journal of Pharmacology (2004) 141, 407–414. doi:10.1038/sj.bjp.0705632
Octreotide regulates CC but not CXC LPS‐induced chemokine secretion in rat Kupffer cells
Authors: Valatas Vassilis , Kolios George , Manousou Pinelopi , Notas George , Xidakis Costas , Diamantis Ioannis , Kouroumalis Elias 
Published: February 2004

Kupffer cells (KC) and lipopolysaccharide (LPS) interaction is the initial event leading to hepatic inflammation and fibrosis in many types of liver injury. We studied chemokine secretion by KC activated with LPS and the possible effect of the somatostatin analogue octreotide, in the regulation of this process.
KC isolated from Sprague–Dawley rats were cultured in the presence of LPS added alone or with different concentrations of octreotide for 24 and 48 h, and chemokine production was assessed in culture supernatants by ELISA. CC chemokine mRNA expression was assessed by semiquantitative RT–PCR.
Vehicle‐stimulated KC produced a basal amount of CC and CXC chemokines. LPS‐stimulated KC secreted significantly increased amounts of IL‐8 (GRO/CINC‐1) (P<0.001), MIP‐2 (P<0.001), MCP‐1 (P<0.001), and RANTES (P<0.01).
Octreotide inhibited LPS‐induced secretion of the CC chemokines MCP‐1 (P<0.05) and RANTES (P<0.05), but not the CXC chemokines IL‐8 (GRO/CINC‐1) and MIP‐2, in a concentration‐dependent manner. Downregulation of basal and LPS‐induced mRNA expression of the CC chemokines was also observed in the presence of octreotide.
Pretreatment with phosphatidylinositol 3 (PI3)‐kinase inhibitors reduced chemokine production by LPS‐treated KC in both the mRNA and protein level. Furthermore, it prevented the octreotide inhibitory effect on LPS‐induced chemokine secretion, indicating a possible involvement of the PI3‐kinase pathway.
In conclusion, these data demonstrate that chemokine secretion by KC can be differentially regulated by octreotide, and suggest that this somatostatin analogue may have immunoregulatory effects on resident liver macrophages.

British Journal of Pharmacology (2004) 141, 477–487. doi:10.1038/sj.bjp.0705633
Differential effects of P2Y1 and P2Y12 nucleotide receptors on ERK1/ERK2 and phosphatidylinositol 3‐kinase signalling and cell proliferation in serum‐deprived and nonstarved glioma C6 cells
Authors: Czajkowski Rafał , Banachewicz Wiktor , Ilnytska Olga , Drobot Ludmila B , Barańska Jolanta 
Published: February 2004

We have previously shown that, in glioma C6 cells, two nucleotide ADP‐sensitive receptors coexist: P2Y1, coupled to PLC and responsible for Ca2+ release, and P2Y12, negatively coupled to adenylate cyclase. In the present study, we examined the effects of the stimulation of these two receptors on ERK1/2 and PI3‐K activation, and cell proliferation in either serum‐deprived or nonstarved C6 cells.
In response to ADP and its analogues, in serum‐starved cells, both p44 ERK1 and p42 ERK2 were activated in a time‐dependent manner, as monitored by Western blot analysis using an antiphospho‐p42/p44 MAPK antibody. The phosphorylation was reduced both by removal of the extracellular Ca2+ and partially or almost completely by MRS2179 or AR‐C69931MX, specific antagonists of the P2Y1 and P2Y12 receptors, respectively. The inhibitory effect of antagonists was additive. These data indicate the involvement of both receptors, P2Y1 and P2Y12, in the ERK1/2 activation, but the P2Y12 receptor contribution predominates.
ERK1/2 activity was positively correlated with cell proliferation of cultured glioma C6 cells.
In nonstarved cells, ADP markedly decreased the PI3‐K activity. In contrast, in serum‐starved cells, ADP evoked an increase in the PI3‐K activity. Blocking of the P2Y1 receptor by MRS2179 additionally increased this ADP response. These results suggest that the P2Y1 receptor has an inhibitory and the P2Y12 receptor a stimulatory effect on PI3‐K signalling pathway.
RT–PCR analysis revealed different mRNA expression of both receptors in starved and nonstarved cells. In nonstarved cells, the P2Y1 receptor mRNA predominates, whereas in serum‐deprived cells the expression of P2Y12 mRNA becomes more pronounced.

British Journal of Pharmacology (2004) 141, 497–507. doi:10.1038/sj.bjp.0705639
The contractile action of leukotriene B4 in the guinea‐pig lung involves a vascular component
Authors: Sakata Kiyoto , Dahlén Sven‐Erik , Bäck Magnus 
Published: February 2004

Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant, acting on specific receptors, BLT receptors. The aim of this study was to examine the mechanism of action of LTB4 in the guinea‐pig lung, using strips of lung parenchyma (GPLP), spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA). Mechanical responses were studied in organ baths, and mediator release was assessed using enzyme immuno assay.
LTB4 induced similar contractions of GPLP and GPPA, whereas LTB4 had only small contractile effects in GPT and GPB. In addition, the contractile response to LTB4 was reproduced in the human pulmonary artery.
In the GPLP, the unselective BLT receptor antagonist ONO‐4057 abolished the contractions induced by LTB4, whereas the selective BLT1 receptor antagonist U–75302 only partly inhibited the LTB4‐induced contractions. In the GPPA, both antagonists abolished the response to LTB4.
The effect of LTB4 in GPPA and GPLP was indirect and mediated by the release of thromboxane A2 and histamine, as supported by selective pharmacologic interventions and measurements of thromboxane B2 and histamine in the organ baths.
In conclusion, the results indicate a new biological function of LTB4, namely to constrict isolated pulmonary arteries. Moreover, the findings suggest that the LTB4‐induced contractions of GPPA were mediated by a BLT1 receptor, whereas BLT2 receptor activation accounted for a major part of the contraction of GPLP, making the latter preparation a suitable assay for BLT2 receptors.

British Journal of Pharmacology (2004) 141, 449–456. doi:10.1038/sj.bjp.0705641
Structure–activity analysis of a novel NR2C/NR2D‐preferring NMDA receptor antagonist: 1‐(phenanthrene‐2‐carbonyl) piperazine‐2,3‐dicarboxylic acid
Authors: Feng Bihua , Tse Heong W , Skifter Donald A , Morley Richard , Jane David E , Monaghan Daniel T 
Published: February 2004

(2S*,3R*)‐1‐(biphenyl‐4‐carbonyl)piperazine‐2,3‐dicarboxylic acid (PBPD) is a moderate affinity, competitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist with an atypical pattern of selectivity among NMDA receptor 2 subunit (NR2) subunits. We now describe the activity of several derivatives of PBPD tested at both rat brain NMDA receptors using L‐[3H]‐glutamate binding assays and at recombinant receptors expressed in Xenopus oocytes.
Substituting various branched ring structures for the biphenyl group of PBPD reduced NMDA receptor activity. However, substituting linearly arranged ring structures – fluorenone or phenanthrene groups – retained or enhanced activity.
Relative to PBPD, the phenanthrene derivative (2S*,3R*)‐1‐(phenanthrene‐2‐carbonyl)piperazine‐2,3‐dicarboxylic acid (PPDA) displayed a 30‐ to 78‐fold increase in affinity for native NMDA receptors. At recombinant receptors, PPDA displayed a 16‐fold (NR2B) to 94‐fold (NR2C) increase in affinity over PBPD.
Replacement of the biphenyl group of PBPD with a 9‐oxofluorene ring system resulted in small changes in receptor affinity and subtype selectivity.
2′‐Bromo substitution on the biphenyl group of PBPD reduced antagonist affinity 3‐ to 5‐fold at NR2A‐, NR2B‐ and NR2D‐containing receptors, but had little effect on NR2C‐containing receptors. In contrast, 4′‐fluoro substitution of the biphenyl ring of PBPD selectively increased NR2A affinity.
The aromatic rings of PBPD and PPDA increase antagonist affinity and appear to interact with a region of the NMDA receptor displaying subunit heterogeneity. PPDA is the most potent and selective NR2C/NR2D‐preferring antagonist yet reported and thus may be useful in defining NR2C/NR2D function and developing related antagonists with improved NMDA receptor subtype selectivity.

British Journal of Pharmacology (2004) 141, 508–516. doi:10.1038/sj.bjp.0705644
Effects of variation among plant species on the interaction between a herbivore and its parasitoid
Authors: Helms Sandra E. , Connelly Scott J. , Hunter Mark D. 
Published: February 2004

Abstract.  1. Previous studies have demonstrated that phenotypic traits of plants have the potential to affect interactions between herbivores and their natural enemies. Consequently, the impact of natural enemies on herbivore vital rates and population dynamics may vary among plant species. This study was designed to investigate the potential for density‐dependent parasitism of an aphid herbivore feeding on six different host plant species.2. Population densities of the aphid Aphis nerii B de F (Homoptera: Aphididae) and its parasitoid Lysiphlebus testaceipes Cresson (Hymenoptera: Braconidae) were recorded within a single growing season on six different species of milkweed in the genus Asclepias L. (Asclepiadaceae). Asclepias species are known to vary in their quality as food for herbivores. Although data on plant quality were not available in this study, population data were analysed to determine the effects of different Asclepias species on rates of parasitism and aphid population growth.3. Parasitism rates of A. nerii varied among Asclepias species but were temporally density dependent over at least some range of aphid density on all plant species. Aphid population growth rates also varied among Asclepias species, and declined with an increase in the maximum parasitism rates among plant species; however, in no case was density‐dependent parasitism sufficient to prevent exponential population growth of aphids within the growing season. The results serve to emphasise that, if natural enemies are to regulate herbivore populations, density‐dependent mortality is a necessary, but not sufficient, condition for regulation.
Tracking larval insect movement within soil using high resolution X‐ray microtomography
Authors: Johnson Scott N. , Read Derek B. , Gregory Peter J. 
Published: February 2004

Abstract.  1. In contrast to above‐ground insects, comparatively little is known about the behaviour of subterranean insects, due largely to the difficulty of studying them in situ.2. The movement of newly hatched (neonate) clover root weevil (Sitona lepidus L. Coleoptera: Curculinidae) larvae was studied non‐invasively using recently developed high resolution X‐ray microtomography.3. The movement and final position of S. lepidus larvae in the soil was reliably established using X‐ray microtomography, when compared with larval positions that were determined by destructively sectioning the soil column.4. Newly hatched S. lepidus larvae were seen to attack the root rhizobial nodules of their host plant, white clover (Trifolium repens L.). Sitona lepidus larvae travelled between 9 and 27 mm in 9 h at a mean speed of 1.8 mm h−1.5. Sitona lepidus larvae did not move through the soil in a linear manner, but changed trajectory in both the lateral and vertical planes.
Seasonal extension of the soldier instar as a route to increased defence investment in the social aphid Pemphigus spyrothecae
Authors: Pike N. , Braendle C. , Foster W. A. 
Published: February 2004

Abstract.  1. The possibility that the duration of the soldier instar could be extended over the course of the galling season was examined in Pemphigus spyrothecae Passerini (Hemiptera: Aphididae). In this species, the individuals of one morph of the dimorphic first instar are non‐sterile specialised defenders known as soldiers.2. In the face of a declining birth rate, the proportion of first‐instar soldiers to first‐instar non‐soldiers was found to increase. This provides strong evidence of extension of the soldier instar over time.3. Instar extension provides a mechanism for post‐natal investment in soldiers and allows individuals with insufficient time to mature to remain in the defensive stage so that they may continue to make an indirect contribution to their clone's reproductive success.
Using food for different purposes: female responses to prey in the predator Coccinella septempunctata L. (Coleoptera: Coccinellidae)
Authors: Evans Edward W. , Richards Douglas R. , Kalaskar Anupama 
Published: February 2004

Abstract.  1. Although predatory insects often feed on diverse prey, their reproductive activity may be linked most strongly to a more restricted range of prey. The propensity of adult females of the ladybird beetle, Coccinella septempunctata L., to attack two natural prey species, pea aphids [Acyrthosiphon pisum (Harris)] and alfalfa weevil larvae [Hypera postica (Gyllenhal)], was compared, and the degree to which ladybird egg production depends on consumption of aphids vs. weevils was assessed.2. Coccinella septempunctata females more readily attacked aphids than weevil larvae. This was true regardless of whether females had fed previously on aphids or on weevil larvae.3. When females were provided with few to many aphids daily, or few aphids plus an excess number of weevil larvae, their rates of egg production depended primarily on the number of aphids consumed.4. Addition of weevil larvae to diets of limited numbers of aphids increased egg production, but only modestly. Thus, consumption of weevil larvae may have served mostly for self‐maintenance, thereby enabling females to use for egg production more of the nutrients and energy obtained from limited consumption of aphids.5. The females' linkage of egg production primarily to aphid rather than weevil consumption may be adaptive, as their offspring are much less able as larvae to survive and mature on a diet of weevils rather than aphids.
Development, growth, and egg production of Ageneotettix deorum (Orthoptera: Acrididae) in response to spider predation risk and elevated resource quality
Authors: Danner Bradford. J. , Joern Anthony 
Published: February 2004

Abstract.  1. Predation risk to insects is often size‐ or stage‐selective and usually decreases as prey grow. Any factor, such as food quality, that accelerates developmental and growth rates is likely to reduce the period over which prey are susceptible to size‐dependent predation.2. Using field experiments, several hypotheses that assess growth, development, and egg production rates of the rangeland grasshopper Ageneotettix deorum (Scudder) were tested in response to combinations of food quality and predation risk from wolf spiders to investigate performance variation manifested through a behaviourally mediated path affecting food ingestion rates.3. Grasshoppers with nutritionally superior food completed development ≈ 8–18% faster and grew 15–45% larger in the absence of spiders, in comparison with those subjected to low quality food exposed to spider predators. Growth and development did not differ for grasshoppers feeding on high quality food when predators were present in comparison with lower quality food unimpeded by predators. Responses indicated a compensatory relationship between resource quality and predation risk.4. Surviving grasshoppers produced fewer eggs compared with individuals not exposed to spiders. Because no differences were found in daily egg production rate regardless of predation treatment, lower egg production was attributed to delayed age of first reproduction. Results compare favourably with responses observed in natural populations.5. Risk of predation from spiders greatly reduced growth, development, and ultimately egg production. Increased food quality counteracts the impact of predation risk on grasshoppers through compensatory responses, suggesting that bottom‐up factors mediate effects of spiders.
Accumulating wing damage affects foraging decisions in honeybees (Apis melliferaL.)
Authors: Higginson A. D. , Barnard C. J. 
Published: February 2004

Abstract. 1. Nectar‐foraging honeybees (Apis mellifera) on lavender (Lavandula stoechas) appear to forage so as to maximise net energy return from foraging bouts; however, evidence from other studies suggests that foraging has a detrimental effect on survival, due at least in part to physiological deterioration of the flight mechanism. But foragers also acquire wing damage during foraging, which may increase foraging effort and reduce foraging lifespan.2. The accumulation of damage over time and its effects on foraging flight and flower choice were studied in the field using a system in which the criteria for flower preference by foragers was known from previous work. Wing damage accumulated exponentially over time and resulted in foragers becoming less choosy about the flowers they visited.3. Damage added experimentally contributed independently to the effect on choosiness. Effects of wing damage (natural and added experimentally) were also independent of those of a relative measure of age, which related in an inconsistent way to changes in foraging preferences.
Constraints on the utilisation of the invasive Chinese tallow tree Sapium sebiferum by generalist native herbivores in coastal prairies
Authors: Lankau Richard A. , Rogers William E. , Siemann Evan 
Published: February 2004

Abstract.  1. Introduced plants generally have lower generalist herbivore loads than native plants. Herbivores may be avoiding a potentially edible food source (Behavioural Constraint Hypothesis) or defences of introduced plants may be unusually toxic (Novel Defence Hypothesis).2. To examine these hypotheses, acridid grasshoppers (Melanoplus angustipennis and Orphullela pelidna) were enclosed in a Texas grassland. Each enclosure contained native prairie vegetation and a seedling of either introduced Sapium sebiferum (Chinese tallow tree) or native Celtis laevigata (hackberry). Sapium invades many ecosystems in the south‐east U.S.A. Celtis seedlings also establish in these ecosystems.3. Although grasshoppers usually feed sparingly on Sapium, in field enclosures they fed heavily on this introduced tree species, supporting a role for behavioural avoidance. In laboratory feeding trials, M. angustipennis grasshoppers preferred Sapium foliage over the foliage of three native tree species. In a greenhouse experiment, M. angustipennis individuals fed more on Sapium in prairie mesocosms if they were conditioned on Sapium.4. In another field experiment with single seedlings in enclosures, grasshoppers consumed similar amounts of Sapium from its introduced (Texas, U.S.A.) and native (China) ranges, suggesting that Sapium may have been a suitable host plant since it was introduced. Behavioural avoidance by generalist herbivores may contribute to Sapium's low herbivore load in its introduced range.