bluuebunny/crossref_metadata_2025_split huggingface dataset:
Purine‐ and pyrimidine‐induced responses and P2Y receptor characterization in the hamster proximal urethra
Authors: Pinna Christian , Glass Rainer , Knight Gillian E , Bolego Chiara , Puglisi Lina , Burnstock Geoffrey 
Published: January 2005

Purine and pyrimidine compounds were investigated on hamster proximal urethral circular smooth muscle preparations. In situ hybridization studies were carried out to localize P2Y1, P2Y2, P2Y4 and P2Y6 mRNA. Protein expression was studied using Western blotting analysis with antibodies against P2Y1 and P2Y2 receptors.
The hamster urethra relaxed with an agonist potency order of: 2‐MeSADP>β,γ‐meATP=ATP=adenosine=ADP>2‐MeSATP>α,β‐meATP>TTP>CTP=UTP>GTP=UDP. The high potency of 2‐MeSADP is suggestive of an action via P2Y1 receptors. Although the order is not characteristic for any known single P2Y receptor subtype, it may represent a combination of P2Y receptor subtypes.
The selective P2Y1 receptor antagonist MRS2179 inhibited ATP‐, 2‐MeSADP‐, 2‐MeSATP‐, β,γ‐meATP‐, and to a lesser degree α,β‐meATP‐induced responses.
Adenosine, but not ATP, was inhibited by the adenosine receptor antagonist 8‐phenyltheophylline, indicating that ATP was not acting via adenosine following enzymatic breakdown.
Western blotting analysis showed the expression of both P2Y1 and P2Y2 receptors, confirming the results obtained with in situ hybridization that showed the expression of both P2Y1 and P2Y2, but not P2Y4 or P2Y6 mRNA, in smooth muscle layers of the hamster proximal urethra.
It is proposed that the relaxant response of the urethra to ATP may be evoked through the activation of the combination of receptors for P2Y1 and to a lesser extent P2Y2 receptors, which may mediate a trophic effect in addition. A P2Y subtype responsive to α,β‐meATP and P1 receptors may contribute to urethral smooth muscle relaxation.

British Journal of Pharmacology (2005) 144, 510–518. doi:10.1038/sj.bjp.0706047
Voltage‐dependent inhibition of recombinant NMDA receptor‐mediated currents by 5‐hydroxytryptamine
Authors: Kloda Anna , Adams David J 
Published: January 2005

The effect of 5‐HT and related indolealkylamines on heteromeric recombinant NMDA receptors expressed in Xenopus oocytes was investigated using the two‐electrode voltage‐clamp recording technique.
In the absence of external Mg2+ ions, 5‐HT inhibited NMDA receptor‐mediated currents in a concentration‐dependent manner. The inhibitory effect of 5‐HT was independent of the NR1a and NR2 subunit combination.
The inhibition of glutamate‐evoked currents by 5‐HT was use‐ and voltage‐dependent. The voltage sensitivity of inhibition for NR1a+NR2 subunit combinations by 5‐HT was similar, exhibiting an e‐fold change per ∼20 mV, indicating that 5‐HT binds to a site deep within the membrane electric field.
The inhibition of the open NMDA receptor by external Mg2+ and 5‐HT was not additive, suggesting competition between Mg2+ and 5‐HT for a binding site in the NMDA receptor channel. The concentration‐dependence curves for 5‐HT and 5‐methoxytryptamine (5‐MeOT) inhibition of NMDA receptor‐mediated currents are shifted to the right in the presence of external Mg2+.
The related indolealkylamines inhibited glutamate‐evoked currents with the following order of inhibitory potency: 5‐MeOT=5‐methyltryptamine>tryptamine>7‐methyltryptamine>5‐HT≫tryptophan=melatonin.
Taken together, these data suggest that 5‐HT and related compounds can attenuate glutamate‐mediated excitatory synaptic responses and may provide a basis for drug treatment of excitoxic neurodegeneration.

British Journal of Pharmacology (2005) 144, 323–330. doi:10.1038/sj.bjp.0706049
The composition of the GABA receptor at the Caenorhabditis elegans neuromuscular junction
Authors: Bamber Bruce A , Richmond Janet E , Otto James F , Jorgensen Erik M 
Published: January 2005

The unc‐49 gene of the nematode Caenorhabditis elegans encodes three γ‐aminobutyric acid type A (GABAA) receptor subunits. Two of these, UNC‐49B and UNC‐49C, are expressed at high abundance and co‐localize at the neuromuscular junction.
The UNC‐49B subunit is sufficient to form a GABAA receptor in vitro and in vivo. Furthermore, all loss‐of‐function unc‐49 alleles lack functional UNC‐49B. No mutations specifically inactivate UNC‐49C. Thus, UNC‐49C appears to be dispensable for receptor function; however, UNC‐49C has been conserved among different nematode species, suggesting it plays a necessary role.
To ascertain whether UNC‐49C is part of the GABAA receptor in vivo, we performed patch‐clamp electrophysiology on C. elegans muscle cells. Sensitivity to GABA, and to the antagonists picrotoxin and pregnenolone sulfate, matched the UNC‐49B/C heteromer rather than the UNC‐49B homomer, for both exogenous and synaptically‐released GABA.
The synaptic localization of UNC‐49C requires the presence of UNC‐49B, indicative of a physical association between the two subunits in vivo. Thus, the in vivo receptor is an UNC‐49B/C heteromer.
UNC‐49C plays a negative modulatory role. Using the rapid ligand‐exchange technique in vitro, we determined that UNC‐49C causes accelerated receptor desensitization. Previously, UNC‐49C was shown to reduce single‐channel conductance in UNC‐49B/C heteromers. Thus, the function of UNC‐49B is to provide GABA responsiveness and localization to synapses, while the function of UNC‐49C is to negatively modulate receptor function and precisely shape inhibitory postsynaptic currents.

British Journal of Pharmacology (2005) 144, 502–509. doi:10.1038/sj.bjp.0706052
The soy isoflavone genistein induces a late but sustained activation of the endothelial nitric oxide‐synthase system in vitro
Authors: Räthel Thomas R , Leikert Jürgen F , Vollmar Angelika M , Dirsch Verena M 
Published: January 2005

Cardiovascular diseases are known as the major causes of death or disability in western countries. Decreased bioavailability of endothelial derived nitric oxide (NO) is recognized as an important promoter in cardiovascular disease.
In vivo studies suggest that phytoestrogens, especially isoflavones from soy, enhance endothelium‐dependent vasoreactivity.
We hypothesized that isoflavones may affect the expression of endothelial‐type nitric oxide synthase (eNOS) and thereby NO formation in vitro.
Human EA.hy926 endothelial cells were treated with the soybean isoflavones biochanin A and formononetin and with their metabolites genistein and daidzein. eNOS promoter activity was examined by a luciferase reporter gene assay (20 h). Active eNOS was detected by quantifying conversion of L‐arginine to L‐citrulline and by measuring NO released from endothelial cells using the fluorescent probe DAF‐2 (20–96 h).
eNOS promoter activity increased in response to isoflavone treatment (20 h). NO and L‐citrulline production by EA.hy926 cells rose up to 1.7‐fold of control levels after stimulation with genistein for 48–96 h. From these results, we conclude that the suggested positive effects of soy isoflavones on vascular reactivity may be indeed mediated via a long‐term effect on the eNOS system.

British Journal of Pharmacology (2005) 144, 394–399. doi:10.1038/sj.bjp.0706075
The expanding field of cannabimimetic and related lipid mediators
Authors: Bradshaw Heather B , Walker J Michael 
Published: January 2005

The discovery of the endogenous cannabimimetic lipid mediators, anandamide and 2‐arachidonoyl glycerol, opened the door to the discovery of other endogenous lipid mediators similar in structure and function. The majority of these compounds do not bind appreciably to known cannabinoid receptors; yet some of them produce cannabimimetic effects while others exert actions through novel mechanisms that remain to be elucidated. This review explores the growing diversity of recently discovered putative lipid mediators and their relationship to the endogenous cannabinoid system. The possibility that there remain many unidentified signalling lipids coupled with the evidence that many of these yield bioactive metabolites due to actions of known enzymes (e.g. cyclooxygenases, lipoxygenases, cytochrome P450s) suggests the existence of a large and complex family of lipid mediators about which only little is known at this time. The elucidation of the biochemistry and pharmacology of these compounds may provide therapeutic targets for a variety of conditions including sleep dysfunction, eating disorders, cardiovascular disease, as well as inflammation and pain.British Journal of Pharmacology (2005) 144, 459–465. doi:10.1038/sj.bjp.0706093
Systems analysis of RNA trafficking in neural cells
Authors: Carson John H. , Barbarese Elisa 
Published: January 2005

AbstractIn neural cells, certain RNAs are targeted to dendrites by a specific RNA trafficking pathway, termed the A2 pathway, mediated by the trans‐acting trafficking factor, heterogeneous nuclear ribonucleoprotein (hnRNP) A2, which binds to an 11 nucleotide cis‐acting trafficking sequence, termed the hnRNP A2 response element (A2RE). RNAs containing A2RE‐like sequences are recognized by hnRNP A2 in the nucleus and exported to the cytoplasm where they assemble into trafficking intermediates, termed granules, which also contain components of the translation machinery and molecular motors (cytoplasmic dynein and conventional kinesin). RNA granules move along microtubules to the cell periphery where they become localized and where the encoded protein is translated. Intracellular trafficking of RNA molecules by the A2 pathway is mediated by a complex system consisting of five different subsystems, ∼35 different molecules and ∼45 different molecular interactions. Specificity in the A2 pathway is provided by specific interactions of hnRNP A2 with different molecular partners in different subsystems. Polarity of RNA trafficking is controlled by transitions of trafficking intermediates between different subsystems. Comprehensive understanding of the A2 RNA trafficking pathway will require quantitative analysis of concentrations and diffusion constants for each of the different molecules, on rates and off rates for each of the different interactions, relevant conditional operators controlling specific interactions, and interactions of different subsystems. Once the necessary quantitative data are available, mathematical models for the different RNA trafficking subsystems can be developed using computational platforms such as the ‘Virtual Cell’. Here we describe how each of the subsystems in the A2 system functions and how the different subsystems interact to regulate RNA trafficking.
Pace Mapping of Koch's Triangle Reduces Risk of Atrioventricular Block During Ablation of Atrioventricular Nodal Reentrant Tachycardia
Authors: DELISE PIETRO , SITTA NADIR , BONSO ALDO , CORO' LEONARDO , FANTINEL MAURO , MANTOVAN ROBERTO , SCIARRA LUIGI , ZOPPO FRANCO , VERLATO ROBERTO , MARRAS ELENA , D'ESTE DANIELE 
Published: January 2005

Introduction: Slow pathway (SP) ablation of AV nodal reentrant tachycardia (AVNRT) can be complicated by second‐ to third‐degree AV block. We assessed the usefulness of pace mapping of Koch's triangle in preventing this complication. Methods and Results: Nine hundred nine consecutive patients undergoing radiofrequency ablation of AVNRT were analyzed. Group 1 (n = 487) underwent conventional slow pathway ablation. Group 2 (n = 422) underwent ablation guided by pace mapping of Koch's triangle, which located the anterogradely conducting fast pathway (AFP) based on the shortest St‐H interval obtained by stimulating the anteroseptal, midseptal, and posteroseptal aspects of Koch's triangle. In group 2, AFP was anteroseptal in 384 (91%), midseptal in 33 (7.8%), and posteroseptal or absent in 5 (1.2%). In 32 of 33 patients with midseptal AFP, slow pathway ablation was performed strictly in the posteroseptal area. In 4 of 5 patients with posteroseptal or no AFP, retrograde fast pathway was ablated. Two patients refused ablation. Persistent second‐ to third‐degree AV block was induced in 7 (1.4%) of 487 group 1 patients versus 0 (0%) of 422 group 2 patients (P = 0.038). Ablation was successful in all patients in whom ablation was performed. Conclusion: Pace mapping of Koch's triangle identifies patients in whom the AFP is absent or is abnormally close to the slow pathway. In these cases, guiding ablation helps to avoid AV block.
Gender Differences in Electrophysiologic Effects of Mental Stress and Autonomic Tone Inhibition:
Authors: INSULANDER PER , VALLIN HANS 
Published: January 2005

Introduction: Gender differences exist in electrophysiologic properties and the occurrence of certain arrhythmias. Mental stress may trigger serious arrhythmias, including ventricular tachycardias and ventricular fibrillation. This study investigates gender differences in the electrophysiologic effects on different levels of the cardiac conduction system elicited by mental stress and autonomic tone inhibition. Methods and Results: Twenty‐three healthy volunteers (11 male and 12 female) participated in the study. Electrophysiologic and hemodynamic variables were measured at baseline, during mental stress produced by Stroop's color word conflict test (CWT), and after autonomic tone inhibition (ATI) with propranolol (0.15 mg/kg) and atropine (0.02 mg/kg). During CWT, men showed shorter QT and JT durations, whereas women had shorter refractoriness in the atrial tissue and AV node. After ATI, no gender differences in sinus nodal properties were noted, whereas AV nodal refractoriness and conduction time became shorter in women, and QT and JT duration and the refractory period of the right ventricle were shorter in men. Conclusion: In women, mental stress produces a pronounced effect on the AV node and on the sinus node. Men react with a more pronounced effect on ventricular electrophysiologic properties. Certain gender differences in cardiac electrophysiologic properties seem to be intrinsic. After ATI, women have a higher heart rate and shorter AV nodal refractoriness but longer QT and JT intervals and longer effective refractory periods in the right ventricle. These differences may partly explain why certain arrhythmias occur more often in women than in men.
Traditional and Nonlinear Heart Rate Variability Are Each Independently Associated with Mortality after Myocardial Infarction
Authors: STEIN PHYLLIS K. , DOMITROVICH PETER P. , HUIKURI HEIKKI V. , KLEIGER ROBERT E. ,   Cast Investigators
Published: January 2005

Introduction: Decreased heart rate variability (HRV) and abnormal nonlinear HRV shortly after myocardial infarction (MI) are risk factors for mortality. Traditional HRV predicts mortality in patients with a range of times post‐MI, but the association of nonlinear HRV and outcome in this population is unknown. Methods and Results: HRV was determined from 740 tapes recorded before antiarrhythmic therapy in Cardiac Arrhythmia Suppression Trial patients with ventricular premature contractions (VPCs) suppressed on the first randomized treatment. Patients were 70 ± 121 days post‐MI. Follow up was 362 ± 241 days (70 deaths). The association between traditional time and frequency‐domain HRV and mortality and nonlinear HRV and mortality were compared for the entire population (ALL), those without coronary artery bypass graft post‐MI (no CABG), and those without CABG or diabetes (no CABG, no DIAB) using univariate and multivariate Cox regression analysis. Strength of association was compared by P values and Wald Chi‐square values. Nonlinear HRV included short‐term fractal scaling exponent, power law slope, and SD12 (Poincaré dimension). For ALL and for no CABG, increased daytime SD12 had the strongest association with mortality (P = 0.002 ALL and P < 0.001 no CABG). For no CABG, no DIAB increased 24‐hour SD12 hours had the strongest association (P < 0.001) with mortality. Upon multivariate analysis, increased SD12, decreased ln ULF (ultra low frequency), and history of prior MI and history of congestive heart failure each remained in the model. Conclusion: Nonlinear HRV is associated with mortality post‐MI. However, as with traditional HRV, this is diluted by CABG surgery post‐MI and by diabetes. Results suggest that decreased long‐term HRV and increased randomness of heart rate are each independent risk factors for mortality post‐MI.
Impact of Amiodarone on Electrophysiologic Properties of Pulmonary Veins in Patients with Paroxysmal Atrial Fibrillation
Authors: ROSTOCK THOMAS , SERVATIUS HELGE , RISIUS TIM , VENTURA RODOLFO , WEISS CHRISTIAN , MEINERTZ THOMAS , WILLEMS STEPHAN 
Published: January 2005

Introduction: Pulmonary veins (PVs) are the predominant location of triggers for atrial fibrillation (AF), but little is known about the electrophysiologic properties of PVs. In addition, the influence of amiodarone on the electrophysiologic properties of PVs has not been elucidated. Methods and Results: Fifty‐five patients with symptomatic and drug‐resistant AF were divided into two groups: group 1 patients (n = 29) without antiarrhythmic drug therapy at the time of electrophysiologic study (EPS), and group 2 patients (n = 26) undergoing continuous long‐term treatment with amiodarone. EPS including programmed stimulation of both atria and within the PVs was performed in both groups. In group 1, the effective refractory period (ERP) of all PVs (174 ± 62 msec) was significantly shorter than the ERP of the left atrium ([LA] 254 ± 30 msec, P = 0.0001) and right atrium ([RA] 221 ± 29 msec, P = 0.0001). The same pattern was observed in group 2 (PV: 210 ± 58 msec; LA: 259 ± 35 msec, P = 0.0001; RA: 246 ± 37 msec, P = 0.0255). The ERP of all stimulated PVs was significantly lower in group 1 (174 ± 62 msec) than in group 2 (210 ± 58 msec; P = 0.0001). The ERP of the left superior and right superior PVs and RA but not the left inferior PV and LA were significantly increased in patients treated with amiodarone. Decremental conduction properties were observed in all stimulated PVs, and there were no significantly differences between the maximal decrement of both groups. Conclusion: The distinctive electrophysiologic properties of PVs are emphasized by amiodarone therapy. Long‐term amiodarone treatment is responsible for heterogeneous alteration of the PV electrophysiology, which may account for the individual antiarrhythmic responses in a subset of patients with paroxysmal AF.
“The Enemy of My Enemy Is My Friend” Is the Enemy: Dealing with the War-Provoking Rules of Intent
Authors: Saperstein Alvin M. 
Published: January 2005

A set of rules often invoked to explain or justify the evolution of intentions and the consequent behavior of competitive systems consists of the following: 1. The friend of my friend is my friend. 2. The friend of my enemy is my enemy. 3. The enemy of my friend is my enemy. 4. The enemy of my enemy is my friend. These rules have been modeled as a set of nonlinear, coupled differential equations from which predictions can be derived as to eventual alliance building or conflict in the system, predictions which are quite ominous for the behavior of simple three-body systems. This paper presents illustrations of the application of the rules to international behavior and discusses the relationship between the rules as usually verbally applied and the associated mathematical models. Not all of these rules are equally desirable: behavior in accordance to the fourth rule has led to major difficulties in the “real world.” This fourth rule cannot just be dropped, since the four rules are not independent of each other in the mathematical model. Hence the model must be altered. A simple mathematical modification is suggested which implies increased flexibility in the verbal statement and application of the rules; e.g., the fourth now reads “The enemy of my enemy may be my friend.” The altered model leads to altered predictions of the evolution of intent which are much less ominous for the outcome of three-body competitions.
Time tells: long‐term patterns in the population dynamics of the yew gall midge,Taxomyia taxi(Cecidomyiidae), over 35 years
Authors: Redfern Margaret , Hunter Mark D. 
Published: January 2005

Abstract. 1. Three populations of the yew gall midge,Taxomyia taxi, and its two chalcid parasitoids,Mesopolobus diffinisandTorymus nigritarsus, from Kingley Vale, West Sussex, U.K., were monitored each year between 1966 and 2002.Taxomyia taxi's life cycles are either hemivoltine or univoltine and the parasitoids' are univoltine (T. nigritarsus) or multivoltine (M. diffinis).2. Growth of the host trees, yewTaxus baccata, each year between 1950 and 1997 was assessed by width of annual rings in cores taken in 1998. Temperature and rainfall data were provided by the weather station in Southampton, representative of the climate of central southern England.3. Time‐series analyses were conducted to explore the effects of climate, tree growth, and parasitoids on eachT. taxipopulation and on the three populations combined. Four time‐delayed models were developed: for hemivoltine and univoltineT. taxiand for each of the parasitoids.4. HemivoltineT. taxipopulations showed troughs in density in the periods 1972–1975 and 1991–1992, which were more pronounced in even than odd years; these were closely tracked byM. diffinisand followed, after a delay, byT. nigritarsus. Time‐series models showed that, forT. taxi, its current density depended on the density of its hemivoltine parents moderated by the negative effects ofT. nigritarsuson these parents. In reciprocal fashion,T. nigritarsusdensity was influenced by that of its hemivoltine host as well as by its own previous density. Host and parasitoid appear to participate in a coupled interaction that regulates the populations of both via delayed density dependence, resulting in cycles of at least 14 years.Mesopolobus diffinishad no effect on the dynamics of hemivoltineT. taxi, most of which escaped its parasitism. Although univoltineT. taxican give rise to hemivoltine offspring, there was no evidence that they affected hemivoltine dynamics.5. The density of univoltineT. taxiwas usually much lower than hemivoltine density and varied irregularly over time. It was not attacked byT. nigritarsusbut parasitism byM. diffiniswas always high. Despite this, its density depended only on the density of its parents, especially the hemivoltine parents. Parasitism had no effect on the dynamics of univoltineT. taxi. Conversely,M. diffinisdensity depended solely on the densities of both univoltine and hemivoltine hosts.6. Tree growth appeared to have little effect on the dynamics of the host or parasitoids and there was no evidence that gall density had any effect on growth of the tree. The primary effect of climate appeared to be in maintaining the cyclic nature of theT. taxi–T. nigritarsusinteraction. If stochastic weather variables are removed from the models, the oscillations are of equivalent periodicity but dampen to equilibrium.