bluuebunny/crossref_metadata_2025 huggingface dataset:
Petrogenesis of lavas from Detroit Seamount: Geochemical differences between Emperor Chain and Hawaiian volcanoes
Authors: Huang S. , Regelous M. , Thordarson T. , Frey F. A.
Published: January 2005

The Hawaiian Ridge and Emperor Seamount Chain define a hot spot track that provides an 80 Myr record of Hawaiian magmatism. Detroit Seamount (∼76 to 81 Ma) is one of the oldest Emperor Seamounts. Volcanic rocks forming this seamount have been cored by the Ocean Drilling Program at six locations. Only tholeiitic basalt occurs at Site 884 on the eastern flank and only alkalic basalt, probably postshield lavas, occurs at Sites 883 and 1204 on the summit plateau. However, at Site 1203 the basement core (453 m penetration) includes four thick flows of pahoehoe alkalic basalt underlying ∼300 m of volcaniclastic rocks interbedded with submarine erupted tholeiitic basalt. The geochemical characteristics of these alkalic lavas indicate that phlogopite was important in their petrogenesis; they may represent preshield stage volcanism. The surprising upward transition from subaerial to submarine eruptives implies rapid subsidence of the volcano, which can be explained by the inferred near‐ridge axis setting of the seamount at ∼80 Ma. A near‐ridge axis setting with thin lithosphere is also consistent with a shallow depth of melt segregation for Detroit Seamount magmas relative to Hawaiian magmas, and the significant role for plagioclase fractionation as the Detroit Seamount magmas evolved in the crust. An important long‐term trend along the hot spot track is that 87Sr/86Sr decreases in lavas erupted from ∼40 to 80 Ma. Tholeiitic basalt at Site 884 on Detroit Seamount is the extreme and overlaps with the 87Sr/86Sr‐143Nd/144Nd field of Pacific mid‐ocean ridge basalts (MORB). Complementary evidence for a depleted component in Detroit Seamount lavas is that relative to Hawaiian basalt, Detroit Seamount lavas have lower abundances of incompatible elements at a given MgO content. These lavas, especially from Sites 883 and 884, trend to extremely unradiogenic Pb isotopic ratios which are unlike MORB erupted at the East Pacific Rise. A component with relatively low 87Sr/86Sr and 206Pb/204Pb is required. Lavas erupted from a spreading center in the Garrett transform fault, 13°28′S on the East Pacific Rise, have this characteristic. A plausible hypothesis is mixing of a plume‐related component with a component similar to that expressed in lavas from the Garrett transform fault. However, basaltic glasses from Detroit Seamount also have relatively high Ba/Th, a distinctive characteristic of Hawaiian lavas. We argue that all Detroit Seamount lavas, including those from Site 884, are related to the Hawaiian hot spot. Rejuvenated stage Hawaiian lavas also have high Ba/Th and define a trend to low 87Sr/86Sr and 206Pb/204Pb. We speculate that rejuvenated stage lavas and Detroit Seamount lavas sample a depleted mantle component, intrinsic to the plume, over the past 80 Myr.
A proper monsoon index for seasonal and interannual variations of the East Asian monsoon
Authors: Zhu Congwen , Lee Woo‐Sung , Kang Hongwen , Park Chung‐Kyu
Published: January 2005

This study assesses how well the East Asian monsoon index (EAMI), developed on the basis of zonal and meridional land–sea thermal contrasts over the Asia‐Pacific region, can represent the seasonal and interannual variations of the East Asian summer and winter monsoons (EASM and EAWM). It suggests that the EAMI can be used to estimate the timing of the onset and the relative intensity of the EASM, characterized by dominant meridional circulation and rainfall patterns over the Asia‐Pacific region, as well as represent the EAWM, which is dominated by a nearly zonal dipole structure composed of Siberian high and Aleutian low prevailing in the middle and high latitudes. The EAMI is therefore of benefit in understanding the seasonal evolution of the East Asian monsoon circulation and interannual variation of the individual monsoons both in summer and in winter.
Numerical models of volcanotectonic earthquake triggering on non‐ideally oriented faults
Authors: Roman Diana C.
Published: January 2005

Calculation of inflation‐induced Coulomb stress changes on faults of varying orientation indicates that local faults of almost any orientation are susceptible to slip in response to dike inflation. Additionally, as dikes typically inflate in the direction of regional minimum compressive stress, the sense of inflation‐induced strike‐slip faulting predicted by Coulomb stress change models is opposite to that expected from regional tectonic forces. Observations of volcanotectonic (VT) earthquake fault‐plane solutions with pressure (p‐) axes oriented ∼90° to regional maximum compression confirm this prediction. In detail, imperfect agreement between Coulomb stress change models and the ranges of fault‐plane orientations observed in VT fault‐plane solution studies and observed locations of VT seismicity indicates that the orientation and location of pre‐existing faults around the conduit ultimately determine the seismic response of host rock to an inflating dike.
On the identification of plasma sheet flapping waves observed by Cluster
Authors: Golovchanskaya I. V. , Maltsev Y. P.
Published: January 2005

Runov et al. [2003] and Sergeev et al. [2003, 2004] have reported on low‐frequency oscillations of the plasma sheet generated by some impulsive source in the center of the magnetospheric tail and propagating toward the flanks, with velocities that range from a few tens to a few hundreds of km/s. To interpret the finding, a number of wave modes have been invoked and then discarded, for either the group velocities or propagation directions were inconsistent with the observations. In the present paper we examine the MHD ballooning‐type waves first described by Safargaleev and Maltsev [1986] who termed them internal “gravitational” waves, as a possible candidate to match the observed flapping motions. The role of gravity is played by the centrifugal force, acting on hot plasma in a curved magnetic field. The corresponding dispersion relation indicates propagation in the positive/negative azimuthal direction with a group velocity dependent on the wave number across the magnetic field, half‐thickness of the current sheet, and thermal velocity of ions in the neutral sheet. The calculated group velocity ranges from 40 to 400 km/s, being consistent with the observations.
Advantageous GOES IR results for ash mapping at high latitudes: Cleveland eruptions 2001
Authors: Gu Yingxin , Rose William I. , Schneider David J. , Bluth Gregg J. S. , Watson I. Matthew
Published: January 2005

The February 2001 eruption of Cleveland Volcano, Alaska allowed for comparisons of volcanic ash detection using two‐band thermal infrared (10–12 μm) remote sensing from MODIS, AVHRR, and GOES 10. Results show that high latitude GOES volcanic cloud sensing the range of about 50 to 65°N is significantly enhanced. For the Cleveland volcanic clouds the MODIS and AVHRR data have zenith angles 6–65 degrees and the GOES has zenith angles that are around 70 degrees. The enhancements are explained by distortion in the satellite view of the cloud's lateral extent because the satellite zenith angles result in a “side‐looking” aspect and longer path lengths through the volcanic cloud. The shape of the cloud with respect to the GOES look angle also influences the results. The MODIS and AVHRR data give consistent retrievals of the ash cloud evolution over time and are good corrections for the GOES data.
The deep feeding system of Vesuvius involved in recent violent strombolian eruptions
Authors: Marianelli P. , Sbrana A. , Métrich N. , Cecchetti A.
Published: January 2005

Mt. Vesuvius has experienced a period of semipersistent volcanic activity over the last three centuries, producing mainly lava effusions and some mixed effusive‐explosive eruptions of higher magnitude. We present a systematic study on major and volatile elements of melt inclusions trapped in olivine crystals peculiar to lapilli fallout emplaced during the more intense episodes of explosive activity. Based on these data, we propose that the deep feeding system active during this period was formed by a vertically extended volume of crust containing interconnected cracks filled by magma, at pressures >200 MPa. The rise of deep CO2‐H2O‐rich magma blobs from this system triggered the high Volcanic Explosivity Index (VEI 2–3) eruptions, provoking the emission of intense lava effusions of degassed magmas and abrupt transition to intense lava fountains and sustained columns.
Horizontal coseismic deformation of the 2003 Bam (Iran) earthquake measured from SPOT‐5 THR satellite imagery
Authors: Binet R. , Bollinger L.
Published: January 2005

On 26 December 2003, a destructive Mw 6.5 earthquake occurred in Kerman province, Iran, killing more than 30,000 people around the ancient city of Bam. We map the fault zone and determine the slip distribution using sub‐pixel correlation of images taken by the SPOT‐5 THR sensor before and after the main shock. Our results show that the surface displacement occurred on a blind fault oriented N174 and located South of Bam. A 15 km along‐strike profile depicts a distribution with a maximum displacement of 1.2 ± 0.15 m near the centre of the fault. The mean slip that we infer (∼0.77 ± 0.05 m) is much higher than the ground displacement measured in the field (∼0.2 m). We suggest that field‐measured displacements are underestimated due to slip accommodation within an 500 m wide shear zone. Furthermore, we demonstrate for the first time the relevancy of 2.5 m SPOT‐5 THR images for sub‐pixel ground displacement measurements.
Sensitivity of thermal tides in the Venus atmosphere to basic zonal flow and Newtonian cooling
Authors: Takagi M. , Matsuda Y.
Published: January 2005

A numerical model is constructed to investigate sensitivity of thermal tides in the Venus atmosphere to distributions of basic mean‐zonal wind and Newtonian cooling rate. It is found that the amplitude and spatial structure of the diurnal tide are strongly influenced by the midlatitudinal jets and the Newtonian cooling rates. In all cases examined in this study, the diurnal tide propagates downward in the lower atmosphere below the cloud levels, and reaches the ground. The semidiurnal tide is generally less dependent on these parameters, but its zonal winds are increased in the upper jet regions.
Differences in the quasi‐biennial oscillation and quasi‐triennial oscillation characteristics of the solar, interplanetary, and terrestrial parameters
Authors: Kane R. P.
Published: January 2005

The 12‐month running means (12 m) and the parameter (12–36 m) representing the quasi‐biennial oscillation (QBO) and quasi‐triennial oscillation (QTO) were examined and spectrally analyzed for several solar, interplanetary, and terrestrial parameters. Solar indices (including solar open magnetic flux in solar latitudes <45°) had a QBO in the form of double peaks separated by ∼2–3 years during sunspot maximum years and smaller waves in other phases of the sunspot cycle. In the interplanetary space a similar structure was seen only in interplanetary total magnetic field B. Interplanetary N and V had long‐term variations different from solar variations. For ground‐level solar proton events as well as all solar proton events observed in satellites and for geomagnetic Dst and Ap, a partial relationship with V (solar wind) is indicated. Cosmic rays observed on Earth seem to have peaks matching with those of solar indices. In the terrestrial atmosphere, stratospheric wind has a predominant QBO similar to solar indices, but the sequence is more uniform than that of the QBO of solar indices. The El Niño‐Southern Oscillation (ENSO) indices (T‐D) and Pacific sea surface temperature have overall characteristics different from those of stratospheric winds or solar indices. Thus there seem to be probably at least four QBO‐QTO regimes, namely those of (1) solar indices at low solar latitudes, (2) interplanetary parameters near Earth, (3) terrestrial low‐latitude stratospheric zonal winds, and (4) terrestrial ENSO phenomena.
Far‐ultraviolet signature of polar cusp during southward IMF Bz observed by TIMED/Global Ultraviolet Imager and DMSP
Authors: Zhang Y. , Meng C.‐I. , Paxton L. J. , Morrison D. , Wolven B. , Kil H. , Newell P. , Wing S. , Christensen A. B.
Published: January 2005

The coincident TIMED/Global Ultraviolet Imager (TIMED/GUVI) optical and DMSP particle observations have revealed new features of the optical signature of the polar cusp under a southward interplanetary magnetic field (IMF). We have found that cusp auroras usually take the shape of a thin arc with a width around 100–200 km. This provides the first far‐ultraviolet evidence of the narrow cusp under a southward IMF [Newell and Meng, 1987]. The cusp auroras could extend down to 0800 magnetic local time (MLT) in the morningside and 1400 MLT in the duskside. Its length is about a few thousand kilometers. A large solar wind density, speed, and IMF are necessary conditions for GUVI to observe the cusp aurora. We found that the cusp location at 1200 MLT changes linearly (−10 nT Bz < 0 nT) and nonlinearly (Bz < −10 nT) with the IMF Bz. The nonlinear effect can be explained by an L−3 dependence of the Earth's equatorial magnetic field.
Pi2 pulsations associated with poleward boundary intensifications during the absence of substorms
Authors: Kim K.‐H. , Takahashi K. , Lee D.‐H. , Sutcliffe P. R. , Yumoto K.
Published: January 2005

Pi2 pulsations during the intervals of extremely quiet geomagnetic conditions (Kp = 0) have been reported by Sutcliffe and Lyons [2002]. These authors observed that several Pi2 bursts occurred simultaneously at high (magnetic latitude = 71°) and low (42°) latitudes during the absence of magnetospheric substorms and found that the bursts are strongly correlated with poleward boundary intensifications (PBIs). The authors discussed the correlation between the PBI‐associated Pi2 (PBI‐Pi2) bursts and enhancements of energetic particle fluxes in the plasma sheet, but they did not focus on the wave properties of the PBI‐Pi2 pulsations. In this study we examine whether the PBI‐Pi2 pulsations at middle/low latitudes exhibit spatial variations similar to substorm‐associated Pi2 pulsations. Using ground‐based data from latitudinally and longitudinally extended magnetometer network and spacecraft data in the duskside, we investigate the spatial variation of the frequency, amplitude, phase, and interstation coherence of the PBI‐Pi2 events. We show that the PBI‐Pi2 pulsations in this study have different features at different local times and suggest that their period and duration are determined at a source region, where fast earthward flows brake.
Direct evidence for magnetic reconnection in the solar wind near 1 AU
Authors: Gosling J. T. , Skoug R. M. , McComas D. J. , Smith C. W.
Published: January 2005

We have obtained direct evidence for local magnetic reconnection in the solar wind using solar wind plasma and magnetic field data obtained by the Advanced Composition Explorer (ACE). The prime evidence consists of accelerated ion flow observed within magnetic field reversal regions in the solar wind. Here we report such observations obtained in the interior of an interplanetary coronal mass ejection (ICME) or at the interface between two ICMEs on 23 November 1997 at a time when the magnetic field was stronger than usual. The observed plasma acceleration was consistent with the Walen relationship, which relates changes in flow velocity to density‐weighted changes in the magnetic field vector. Pairs of proton beams having comparable densities and counterstreaming relative to one another along the magnetic field at a speed of ∼1.4VA, where VA was the local Alfven speed, were observed near the center of the accelerated flow event. We infer from the observations that quasi‐stationary reconnection occurred sunward of the spacecraft and that the accelerated flow occurred within a Petschek‐type reconnection exhaust region bounded by Alfven waves and having a cross section width of ∼4 × 105 km as it swept over ACE. The counterstreaming ion beams resulted from solar wind plasma entering the exhaust region from opposite directions along the reconnected magnetic field lines. We have identified a limited number (five) of other accelerated flow events in the ACE data that are remarkably similar to the 23 November 1997 event. All such events identified occurred at thin current sheets associated with moderate to large changes in magnetic field orientation (98°–162°) in plasmas characterized by low proton beta (0.01–0.15) and high Alfven speed (51–204 km/s). They also were all associated with ICMEs.
Vertical heat and constituent transport in the mesopause region by dissipating gravity waves at Maui, Hawaii (20.7°N), and Starfire Optical Range, New Mexico (35°N)
Authors: Liu Alan Z. , Gardner Chester S.
Published: January 2005

Vertical heat flux profiles induced by dissipating gravity waves in the mesopause region (85–100 km altitude) are derived from Na lidar measurements of winds and temperatures at Maui (20.7°N, 156.3°W), Hawaii, and compared with earlier results from Starfire Optical Range (SOR, 35.0°N, 106.5°W), New Mexico. The heat flux profile at SOR has a single downward maximum of 2.25 ± 0.3 K m/s at 88 km, while the profile at Maui has two downward maxima of 1.25 ± 0.5 K m/s and 1.40 ± 0.5 K m/s at 87 and 95 km, respectively. The common maximum below 90 km can be attributed to high probability of convective instability. Comparison of the horizontal wind shear suggests that the second maximum at 95 km at Maui may be associated with dynamic instability. The measured Na flux and predicted Na flux based on measured heat flux at Maui agree well, further confirming earlier findings using SOR data. The dynamical flux of atomic oxygen estimated from the heat flux is smaller at Maui compared with that at SOR, but both are comparable to or larger than the eddy flux. The results also suggest that weaker gravity wave dissipation at Maui may cause two opposite effects on the energy balance in the mesopause region, a reduced cooling from heat transport and reduced chemical heating from atomic oxygen transport.
Postsynaptic 5‐HT1B receptors modulate electroshock‐induced generalised seizures in rats
Authors: Stean Tania O , Atkins Alan R , Heidbreder Christian A , Quinn Leann P , Trail Brenda K , Upton Neil
Published: January 2005

Although an important regulatory role for serotonin (5‐HT) in seizure activation and propagation is well established, relatively little is known of the function of specific 5‐HT receptor subtypes on seizure modulation.

The aim of the present study was to investigate the role of 5‐HT1A, 1B and 1D receptors in modulating generalised seizures in the rat maximal electroshock seizure threshold (MEST) test.

The mixed 5‐HT receptor agonists SKF 99101 (5–20 mg kg−1 i.p.) and RU 24969 (1–5 mg kg−1 i.p.), 0.5 h pretest, both produced marked dose‐related increases in seizure threshold. These agents share high affinity for 5‐HT1A, 1B and 1D receptors.

Antiseizure effects induced by submaximal doses of these agonists were maintained following p‐chlorophenylalanine (150 mg kg−1 i.p. × 3 days)‐induced 5‐HT depletion.

The anticonvulsant action of both SKF 99101 (15 mg kg−1 i.p.) and RU 24969 (2.5 mg kg−1 i.p.) was dose‐dependently abolished by the selective 5‐HT1B receptor antagonist SB‐224289 (0.1–3 mg kg−1 p.o., 3 h pretest) but was unaffected by the selective 5‐HT1A receptor antagonist WAY 100635 (0.01–0.3 mg kg−1 s.c., 1 h pretest). This indicates that 5‐HT1B receptors are primarily involved in mediating the anticonvulsant properties of these agents.

In addition, the ability of the 5‐HT1B/1D receptor antagonist GR 127935 (0.3–3 mg kg−1 s.c., 60 min pretest) to dose‐dependently inhibit SKF 99101‐induced elevation of seizure threshold also suggests possible downstream involvement of 5‐HT1D receptors in the action of this agonist, although confirmation awaits the identification of a selective 5‐HT1D receptor antagonist.

Overall, these data demonstrate that stimulation of postsynaptic 5‐HT1B receptors inhibits electroshock‐induced seizure spread in rats.

British Journal of Pharmacology (2005) 144, 628–635. doi:10.1038/sj.bjp.0706027
Effects of NS1608, a BKCa channel agonist, on the contractility of guinea‐pig urinary bladder in vitro
Authors: Mora Ticiana Camila , Suarez‐Kurtz Guilherme
Published: January 2005

The functional effects of NS1608 ((N‐(3‐(trifluoromethyl)phenyl)‐N′‐(2‐hydroxy‐5‐chlorophenyl)urea), an opener of the large conductance, Ca2+‐activated K+ (BKCa) channel, on the contractility of guinea‐pig urinary bladder muscle are described.

NS1608 (0.3–30 μM) had no significant effect on the integrated myogenic activity (tension integral) or the electrically evoked twitches of detrusor muscle strips. Possible mechanisms for the discrepancy between the lack of functional effects of NS1608 per se on detrusor contractility and this drug's agonistic effect on BKCa currents in isolated bladder myocytes are discussed.

4‐Aminopyridine (1 mM), a blocker of voltage‐gated K+ (KV) channels, increased the tension integral 2.7‐fold, on average. NS1608 (30 μM) counteracted this effect.

Apamin (100 nM), a selective blocker of the small conductance, Ca2+‐activated K+ (SKCa) channel, increased the tension integral 1.7‐fold, on average. This effect was reversed by NS1608 (30 μM).

Ryanodine (10 μM), a modulator of the sarcoplasmic reticulum (SR) Ca2+‐release channel, increased the tension integral 1.9‐fold, on average. This effect was reversed by NS1608 (30 μM).

Iberiotoxin (IbTX, 50 nM), a selective blocker of the BKCa channel, caused additional increases in the tension integral of detrusor strips pretreated with apamin or ryanodine and prevented the inhibitory effects of NS1608 (30 μM) in detrusor contractility.

The present study shows that blockade of repolarizing currents carried by, respectively apamin‐ and 4‐aminopyridine‐sensitive K+ channels unmasks an activation of BKCa in guinea‐pig urinary bladder smooth muscle strips.

British Journal of Pharmacology (2005) 144, 636–641. doi:10.1038/sj.bjp.0706034
AT2 receptors mediate tonic renal medullary vasoconstriction in renovascular hypertension
Authors: Duke Lisa M , Widdop Robert E , Kett Michelle M , Evans Roger G
Published: January 2005

Renal medullary blood flow is relatively insensitive to angiotensin II (Ang II)‐induced vasoconstriction, due partly to AT1‐mediated release of nitric oxide and/or prostaglandins. AT2‐receptor activation appears to blunt AT1‐mediated vasodilatation within the medullary circulation. This could affect long‐term efficacy of antihypertensive pharmacotherapies targeting the renin/angiotensin system, particularly in Ang II‐dependent forms of hypertension.

We tested the effects of AT1‐ and AT2‐receptor blockade on basal cortical and medullary laser Doppler flux (CLDF and MLDF), and on responses to renal arterial infusion of Ang II, in rats with 2 kidney, 1 clip (2K1C) hypertension and sham‐operated controls. Studies were carried out in thiobutabarbital (175 mg kg−1, i.p.) anaesthetised rats, 4 weeks after clipping, or sham surgery (n=6 in each of eight groups).

Candesartan (10 μg kg−1 h−1, intravenous (i.v.)) reduced mean arterial pressure (∼17%) and increased CLDF (∼24%), similarly in both sham and 2K1C rats, but did not significantly affect MLDF. PD123319 (1 mg kg−1 h−1, i.v.) increased basal MLDF (19%) in 2K1C but not sham rats, without significantly affecting other variables.

In sham rats, renal arterial infusion of Ang II (1–100 ng kg−1 min−1) dose dependently decreased CLDF (up to 44%), but did not significantly affect MLDF. These effects were markedly blunted in 2K1C rats. After PD123319, Ang II dose dependently increased MLDF (up to 38%) in sham but not 2K1C rats. Candesartan abolished all effects of Ang II, including those seen after PD123319.

Our data indicate that AT1 receptors mediate medullary vasodilatation, which is opposed by AT2‐receptor activation. In 2K1C hypertension, AT2‐receptor activation tonically constricts the medullary circulation.

British Journal of Pharmacology (2005) 144, 486–492. doi:10.1038/sj.bjp.0706036
Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A1 and A2A subtype receptor agonists
Authors: Schindler Charles W , Karcz‐Kubicha Marzena , Thorndike Eric B , Müller Christa E , Tella Srihari R , Ferré Sergi , Goldberg Steven R
Published: January 2005

The cardiovascular effects of the adenosine A1 receptor agonist N6‐cyclopentyladenosine (CPA) and the adenosine A2A receptor agonist 2‐p‐(2‐carboxyethyl)phenethylamino‐5′‐N‐ethylcarboxamidoadenosine (CGS 21680) were investigated in rats implanted with telemetry transmitters for the measurement of blood pressure and heart rate.

Intraperitoneal (i.p.) injections of the adenosine A1 receptor agonist CPA led to dose‐dependent decreases in both blood pressure and heart rate. These effects of 0.3 mg kg−1 CPA were antagonized by i.p. injections of the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dimethyl‐xanthine (CPT), but not by i.p. injections of the adenosine A2A receptor antagonist 3‐(3‐hydroxypropyl)‐8‐(m‐methoxystyryl)‐7‐methyl‐1‐propargylxanthine phosphate disodium salt (MSX‐3). Injections (i.p.) of the peripherally acting nonselective adenosine antagonist 8‐sulfophenyltheophylline (8‐SPT) and the purported nonselective adenosine antagonist caffeine also antagonized the cardiovascular effects of CPA.

The adenosine A2A agonist CGS 21680 given i.p. produced a dose‐dependent decrease in blood pressure and an increase in heart rate. These effects of 0.5 mg kg−1 CGS 21680 were antagonized by i.p. injections of the adenosine A2A receptor antagonist MSX‐3, but not by i.p. injections of the antagonists CPT, 8‐SPT or caffeine.

Central administration (intracerebral ventricular) of CGS 21680 produced an increase in heart rate, but no change in blood pressure. MSX‐3 given i.p. antagonized the effects of the central injection of CGS 21680.

These results suggest that adenosine A1 receptor agonists produce decreases in blood pressure and heart rate that are mediated by A1 receptors in the periphery, with little or no contribution of central adenosine A1 receptors to those effects.

The heart rate increasing effect of adenosine A2A agonists appears to be mediated by adenosine A2A receptors in the central nervous system. The blood pressure decreasing effect of adenosine A2A agonists is most probably mediated in the periphery.

British Journal of Pharmacology (2005) 144, 642–650. doi:10.1038/sj.bjp.0706043
Selective release of ATP from sympathetic nerves of rat vas deferens by the toxin TsTX‐I from Brazilian scorpion Tityus serrulatus
Authors: Conceição Isaltino M , Jurkiewicz Aron , Fonseca Daniela R , Opperman Andrea R , Freitas Thalma A , Lebrun Ivo , Garcez‐do‐Carmo Lúcia
Published: January 2005

The effects of the main component of the Tityus serrulatus scorpion venom, toxin TsTX‐I, were studied on the contractility and release of neurotransmitters in the rat vas deferens. Since TsTX‐I is known to act on sodium channels, we used veratridine, another sodium channel agent, for comparison.

Toxin TsTX‐I induced concentration‐dependent contractions with an EC50 value of 47.8±0.1 nM and a maximum effect of 84.4±10.4% of that for BaCl2.

Contractions by TsTX‐I were abolished by denervation or tetrodotoxin (0.1 μM), showing that the toxin effects depend on the integrity of sympathetic nerve terminals.

To check for the presence of a noradrenergic component, experiments were conducted after removal of adrenergic stores in nerve terminals by reserpinization (10 mg kg−1, 24 h prior to experiments) or blockade of α1 adrenoceptors by prazosin (30 μM), showing that these procedures did not modify the response to TsTX‐I, and therefore that adrenoceptors were not involved in contractions.

To check for the presence of a purinergic component, experiments were carried out after blockade of P2X receptors by suramin (0.1 mM) or desensitization by α,β‐methylene‐ATP (30 μM). These agents greatly abolished the contractile response to TsTX‐I (about 83% by desensitization and 96% by suramin), showing the involvement of purinergic receptors.

The release of noradrenaline and purinergic agents (ATP, ADP, AMP and adenosine) was detected by HPLC. Together, the total release of purines in the presence of TsTX‐I was about 42 times higher than in the control group. In contrast, TsTX‐I did not modify the overflow of noradrenaline, showing that the release was selective for purines.

The release of purinergic agents was reduced by the N‐type calcium channel blocker ω‐conotoxin GVIA (1 μM) and by the P/Q‐type blocker ω‐conotoxin MVIIC (1 μM), showing that the effects of TsTX‐I are calcium‐dependent.

The results show that TsTX‐I produced a selective release of purines from postganglionic sympathetic nerves in the rat vas deferens.

British Journal of Pharmacology (2005) 144, 519–527. doi:10.1038/sj.bjp.0706062
Vasomotion: cellular background for the oscillator and for the synchronization of smooth muscle cells
Authors: Aalkjær Christian , Nilsson Holger
Published: January 2005

Vasomotion is the oscillation of vascular tone with frequencies in the range from 1 to 20 min−1 seen in most vascular beds. The oscillation originates in the vessel wall and is seen both in vivo and in vitro.

Recently, our ideas on the cellular mechanisms responsible for vasomotion have improved. Three different types of cellular oscillations have been suggested. One model has suggested that oscillatory release of Ca2+ from intracellular stores is important (the oscillation is based on a cytosolic oscillator). A second proposed mechanism is an oscillation originating in the sarcolemma (a membrane oscillator). A third mechanism is based on an oscillation of glycolysis (metabolic oscillator). For the two latter mechanisms, only limited experimental evidence is available.

To understand vasomotion, it is important to understand how the cells synchronize. For the cytosolic oscillators synchronization may occur via activation of Ca2+‐sensitive ion channels by oscillatory Ca2+ release. The ensuing membrane potential oscillation feeds back on the intracellular Ca2+ stores and causes synchronization of the Ca2+ release. While membrane oscillators in adjacent smooth muscle cells could be synchronized through the same mechanism that sets up the oscillation in the individual cells, a mechanism to synchronize the metabolic‐based oscillators has not been suggested.

The interpretation of the experimental observations is supported by theoretical modelling of smooth muscle cells behaviour, and the new insight into the mechanisms of vasomotion has the potential to provide tools to investigate the physiological role of vasomotion.

British Journal of Pharmacology (2005) 144, 605–616. doi:10.1038/sj.bjp.0706084
Addition of a signal peptide sequence to the α1D‐adrenoceptor gene increases the density of receptors, as determined by [3H]‐prazosin binding in the membranes
Authors: Petrovska Ramona , Kapa Ivo , Klovins Janis , Schiöth Helgi B , Uhlén Staffan
Published: January 2005

Both in mammalian tissues and in transfected cells, only low levels of α1D‐adrenoceptors are detected in radioligand binding studies. It has been implicated that the comparatively long N‐terminal tail of the α1D‐adrenoceptor is responsible for the inefficient surface expression of the receptor.

In the present study, we created gene constructs for six N‐terminally truncated variants of the human α1D‐adrenoceptor. These constructs were used to transfect Neuro2A cells. We show that the density of α1D‐adrenoceptors, observed by [3H]‐prazosin binding, gradually increased with longer truncations of the N‐terminus. This seems to indicate that the long N‐terminal tail nonspecifically interferes with receptor translocation to the plasma membrane.

The addition of a 16 amino acids long signal peptide to the N‐terminus of the wild‐type α1D‐adrenoceptor increased the density of receptor binding sites 10‐fold in Neuro2A and COS‐7 cells. This indicates that, after the addition of a signal peptide, the long N‐terminal tail of the α1D‐adrenoceptor does not interfere with proper translocation of the receptor to the plasma membrane. This, in turn, indicates that the N‐terminal tail of the wild‐type α1D‐adrenoceptor, merely by its long length, hinders the first transmembrane helix of the receptor from being a signal anchor.

Neither the wild‐type α1D‐adrenoceptor (for which the expression level of [3H]‐prazosin binding sites is low) nor the truncated α1D‐adrenoceptor variant (for which the expression level of [3H]‐prazosin binding sites is high) showed any constitutive activity in stimulating inositol phosphate accumulation. This indicates that the low expression level of [3H]‐prazosin binding sites, after transfection with the wild‐type α1D‐adrenoceptor, is not caused by constitutive activity of the receptor and subsequent receptor downregulation.

British Journal of Pharmacology (2005) 144, 651–659. doi:10.1038/sj.bjp.0706087
Effects of connexin‐mimetic peptides on gap junction functionality and connexin expression in cultured vascular cells
Authors: Martin Patricia E M , Wall Colin , Griffith Tudor M
Published: January 2005

We have investigated the effects of connexin‐mimetic peptides homologous to the Gap 26 and Gap 27 domains of Cxs 37, 40 and 43 against gap junctional communication and connexin expression in rat aortic endothelial cells (RAECs) and A7r5 myocytes.

Immunostaining and Western blot analysis confirmed the presence of gap junction plaques containing Cx43, but not Cx40, in RAECs, whereas plaques containing Cxs 40 and 43 were evident in A7r5 cells. Expression of Cx37 was limited in RAECs and absent from A7r5 cells.

Under control conditions calcein‐loaded RAECs transferred dye to ∼70% of subjacent A7r5 cells after coculture for 4–5 h. Dye transfer was inhibited by a peptide targeted to Cxs 37 and 43 (37,43Gap 27), but minimally affected by peptides targeted to Cxs 37 and 40 (37,40Gap 26 and 40Gap 27). These findings suggest that the myoendothelial gap junctions that couple RAECs and A7r5 cells are constructed principally from Cx43.

Inhibition of dye transfer from RAECs to A7r5 cells cocultured in the presence of 37,43Gap 27 plus 37,40Gap 26 for 5 h was fully reversible.

In A7r5 cells, endogenous expression of Cx40 and Cx43 was unaffected by incubation with 37,43Gap 27, 37,40Gap 26, either individually or in combination, and the peptide combination did not impair connexin trafficking or the de novo formation of gap plaques in A7r5 cells transfected to express Cx43‐GFP.

Treatment of A7r5 cells with 37,43Gap 27 plus 37,40Gap 26 abolished synchronized oscillations in intracellular [Ca2+] induced by the α1‐adrenoceptor agonist phenylephrine.

The reversibility and lack of effect of the peptides on plaque formation suggests that they may be considered ideal probes for functional studies of connexin‐mediated communication in the vascular wall.

British Journal of Pharmacology (2005) 144, 617–627. doi:10.1038/sj.bjp.0706102
SEA0400, a specific inhibitor of the Na+–Ca2+ exchanger, attenuates sodium nitroprusside‐induced apoptosis in cultured rat microglia
Authors: Nagano Takayuki , Osakada Masakazu , Ago Yukio , Koyama Yutaka , Baba Akemichi , Maeda Sadaaki , Takemura Motohiko , Matsuda Toshio
Published: January 2005

Using SEA0400, a potent and selective inhibitor of the Na+–Ca2+ exchanger (NCX), we examined whether NCX is involved in nitric oxide (NO)‐induced disturbance of endoplasmic reticulum (ER) Ca2+ homeostasis followed by apoptosis in cultured rat microglia.

Sodium nitroprusside (SNP), an NO donor, decreased cell viability in a dose‐ and time‐dependent manner with apoptotic cell death in cultured microglia.

Treatment with SNP decreased the ER Ca2+ levels as evaluated by measuring the increase in cytosolic Ca2+ level induced by exposing cells to thapsigargin, an irreversible inhibitor of ER Ca2+‐ATPase.

The treatment with SNP also increased mRNA expression of CHOP and GPR78, makers of ER stress.

SEA0400 at 0.3–1.0 μM protected microglia against SNP‐induced apoptosis.

SEA0400 blocked not only the SNP‐induced decrease in ER Ca2+ levels but also SNP‐induced increase in CHOP and GRP78 mRNAs.

SEA0400 did not affect capacitative Ca2+ entry in the presence and absence of SNP.

SNP increased Na+‐dependent 45Ca2+ uptake and this increase was blocked by SEA0400.

These results suggest that SNP induces apoptosis via the ER stress pathway and SEA0400 attenuates SNP‐induced apoptosis via suppression of the ER stress in cultured microglia. Our findings imply that NCX plays a role in ER Ca2+ depletion under pathological conditions.

British Journal of Pharmacology (2005) 144, 669–679. doi:10.1038/sj.bjp.0706104
Andrographolide interferes with binding of nuclear factor‐κB to DNA in HL‐60‐derived neutrophilic cells
Authors: Hidalgo María A , Romero Alex , Figueroa Jaime , Cortés Patricia , Concha Ilona I , Hancke Juan L , Burgos Rafael A
Published: January 2005

Andrographolide, the major active component from Andrographis paniculata, has shown to possess anti‐inflammatory activity. Andrographolide inhibits the expression of several proinflammatory proteins that exhibit a nuclear factor kappa B (NF‐κB) binding site in their gene.

In the present study, we analyzed the effect of andrographolide on the activation of NF‐κB induced by platelet‐activating factor (PAF) and N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) in HL‐60 cells differentiated to neutrophils.

PAF (100 nM) and fMLP (100 nM) induced activation of NF‐κB as determined by degradation of inhibitory factor B α (IκBα) using Western blotting in cytosolic extracts and by binding to DNA using electrophoretic mobility shift assay (EMSA) in nuclear extracts.

Andrographolide (5 and 50 μM) inhibited the NF‐κB‐luciferase activity induced by PAF. However, andrographolide did not reduce phosphorylation of p38 MAPK or ERK1/2 and did not change IκBα degradation induced by PAF and fMLP.

Andrographolide reduced the DNA binding of NF‐κB in whole cells and in nuclear extracts induced by PAF and fMLP.

Andrographolide reduced cyclooxygenase‐2 (COX‐2) expression induced by PAF and fMLP in HL‐60/neutrophils.

It is concluded that andrographolide exerts its anti‐inflammatory effects by inhibiting NF‐κB binding to DNA, and thus reducing the expression of proinflammatory proteins, such as COX‐2.

British Journal of Pharmacology (2005) 144, 680–686. doi:10.1038/sj.bjp.0706105
Effects of statins on vascular function of endothelin‐1
Authors: Mraiche Fatima , Cena Jonathan , Das Debarsi , Vollrath Bozena
Published: January 2005

Although statins have been reported to inhibit the prepro‐endothelin‐1 (ET‐1) gene transcription in endothelial cells, their effects on the vascular function of ET‐1 have not been explored. We, therefore, examined the effects of statins on contraction and DNA synthesis mediated by ET‐1 in vascular smooth muscle. The effects of statins on contraction induced by ET‐1 were compared to those mediated by noradrenaline (NA) and KCl.

Simvastatin (SV) induced a concentration‐dependent relaxation of tonic contraction mediated by ET‐1 (10 nM) (IC50 value of 1.3 μM). The relaxation was also observed in rings precontracted with NA (0.1 μM) and KCl (60 mM). In contrast, pravastatin did not have any effect on the contractions.

Endothelial denudation or pretreatment with L‐NAME did not prevent the relaxation, but did reduce the relaxant activity of SV.

SV prevented Rho activation caused by ET‐1 and KCl in aortic homogenates, as assessed by a Rho pulldown assay.

The Rho kinase inhibitor HA‐1077 mimicked the effects of SV on tonic contractions induced by ET‐1, NA and KCl.

Pretreatment with the Kv channels inhibitor, 4‐aminopyridine, attenuated the ability of SV to relax contractions mediated by ET‐1 and NA.

In quiescent VSM cells, SV significantly inhibited DNA synthesis and Rho translocation stimulated by ET‐1, as assessed by [3H]thymidine incorporation and Western blot, respectively.

Inhibition of Rho geranylgeranylation by GGTI‐297, or treatment with HA‐1077, mimicked the effects of SV on DNA synthesis stimulated by ET‐1.

The results show that the statin potently inhibits both ET‐1‐mediated contraction and DNA synthesis via multiple mechanisms. Clinical benefits of statins may result, in part, from their effects on vascular function of ET‐1.

British Journal of Pharmacology (2005) 144, 715–726. doi:10.1038/sj.bjp.0706114
Interleukin-1 and the Interleukin-1 Type 1 Receptor are Essential for the Progressive Neurodegeneration that Ensues Subsequent to a Mild Hypoxic/Ischemic Injury
Authors: Basu Anirban , Lazovic Jelena , Krady J Kyle , Mauger David T , Rothstein Raymond P , Smith Michael B , Levison Steven W
Published: January 2005

Excessive inflammation has been implicated in the progressive neurodegeneration that occurs in multiple neurological diseases, including cerebral ischemia, and elevated levels of the proinflammatory cytokine interleukin-1 (IL-1) have been shown to exacerbate brain damage, whereas diminishing IL-1 levels limits the extent of injury. However, to date there is no consensus regarding which receptor(s) mediates the detrimental effects of IL-1. Because we have previously demonstrated that signaling through the IL-1 type 1 receptor (IL-1R1) is necessary for microglial activation and because results from other studies have implicated microglia as effectors of neurodegeneration, we hypothesized that inactivating the IL-1R1 would decrease the extent of damage caused by a hypoxic-ischemic (H/I) insult. It is shown that a mild insult initiates progressive neurodegeneration that leads to cystic infarcts, which can be prevented by inactivating the IL-1R1. The IL-1R1 null mice also show preserved sensorimotor function at 1 month's recovery. The mild insult induces multiple proinflammatory cytokines and activates microglia, and these responses are dramatically curtailed in mice lacking the IL-1R1. Importantly, the neuroinflammation precedes the progressive enlargement of the infarct, suggesting that the inflammation is causal rather than a consequence of the brain damage. These findings show that abrogating the inflammation consequent to a mild H/I insult will prevent brain damage and preserve neurological function. Additionally, these data incriminate the IL-1R1 as a master proinflammatory cytokine receptor.
Damage to the Endoplasmic Reticulum and Activation of Apoptotic Machinery by Oxidative Stress in Ischemic Neurons
Authors: Hayashi Takeshi , Saito Atsushi , Okuno Shuzo , Ferrand-Drake Michel , Dodd Robert L , Chan Pak H
Published: January 2005

The endoplasmic reticulum (ER), which plays a role in apoptosis, is susceptible to oxidative stress. Because superoxide is produced in the brain after ischemia/reperfusion, oxidative injury to this organelle may be implicated in ischemic neuronal cell death. Activating transcription factor-4 (ATF-4) and C/EBP-homologous protein (CHOP), both of which are involved in apoptosis, are induced by severe ER stress. Using wild-type and human copper/zinc superoxide dismutase transgenic rats, we observed induction of these molecules in the brain after global cerebral ischemia and compared them with neuronal degeneration. In ischemic, wild-type brains, expression of ATF-4 and CHOP was increased in the hippocampal CA1 neurons that would later undergo apoptosis. Transgenic rats had a mild increase in ATF-4 and CHOP and minimal neuronal degeneration, indicating that superoxide was involved in ER stress-induced cell death. We further confirmed attenuation on induction of these molecules in transgenic mouse brains after focal ischemia. When superoxide was visualized with ethidium, signals for ATF-4 and superoxide overlapped in the same cells. Moreover, lipids in the ER were robustly peroxidized by ischemia but were attenuated in transgenic animals. This indicates that superoxide attacked and damaged the ER, and that oxidative ER damage is implicated in ischemic neuronal cell death.
Na+-Dependent Chloride Transporter (NKCC1)-Null Mice Exhibit Less Gray and White Matter Damage after Focal Cerebral Ischemia
Authors: Chen Hai , Luo Jing , Kintner Douglas B , Shull Gary E , Sun Dandan
Published: January 2005

We previously demonstrated that pharmacological inhibition of Na+−K+−Cl− cotransporter isoform 1 (NKCC1) is neuroprotective in in vivo and in vitro ischemic models. In this study, we investigated whether genetic ablation of NKCC1 provides neuroprotection after ischemia. Focal ischemia was induced by 2 hours occlusion of the left middle cerebral artery (MCAO) followed by 10 or 24 hours reperfusion. Two hours MCAO and ten or twenty-four hours reperfusion caused infarction (˜85 mm3) in NKCC1 wild-type (NKCC1+/+) mice. Infarction volume in NKCC1−/− mice was reduced by ˜30% to 46%. Heterozygous mutant (NKCC1+/–) mice showed ˜28% reduction in infarction ( P>0.05). Two hours MCAO and twenty-four hours reperfusion led to a significant increase in brain edema in NKCC1+/+ mice. In contrast, NKCC1+/– and NKCC1−/− mice exhibited ˜50% less edema ( P<0.05). Moreover, white matter damage was assessed by immunostaining of amyloid precursor protein (APP). An increase in APP was detected in NKCC1+/+ mice after 2 hours MCAO and 10 hours reperfusion. However, NKCC1−/− mice exhibited significantly less APP accumulation ( P<0.05). Oxygen-glucose deprivation (OGD) induced ˜67% cell death and a fourfold increase in Na+ accumulation in cultured NKCC1+/+ cortical neurons. OGD-mediated cell death and Na+ influx were significantly reduced in NKCC1−/− neurons ( P<0.05). In addition, inhibition of NKCC1 by bumetanide resulted in similar protection in NKCC1+/+ neurons and astrocytes ( P<0.05). These results imply that stimulation of NKCC1 activity is important in ischemic neuronal damage.
Long-Term Neuroprotection with 2-Iminobiotin, An Inhibitor of Neuronal and Inducible Nitric Oxide Synthase, after Cerebral Hypoxia-Ischemia in Neonatal Rats
Authors: Tweel Evelyn RW van den , van Bel Frank , Kavelaars Annemieke , Peeters-Scholte Cacha MPCD , Haumann Johan , Nijboer Cora HA , Heijnen Cobi J , Groenendaal Floris
Published: January 2005

The short- and long-term neuroprotective effects of 2-iminobiotin, a selective inhibitor of neuronal and inducible nitric oxide synthase, were studied in 12-day-old rats following hypoxia-ischemia. Hypoxia-ischemia was induced by occlusion of the right carotid artery followed by 90 minutes of hypoxia (FiO2 0.08). Immediately on reoxygenation, 12 and 24 hours later the rats were treated with vehicle or 2-iminobiotin at a dose of 5.5, 10, 30, or 60 mg/kg per day. Histologic analysis of brain damage was performed at 6 weeks after hypoxia-ischemia. To assess early changes of cerebral tissue, levels of HSP70, nitrotyrosine, and cytochrome c were determined 24 hours after reoxygenation. Significant neuroprotection was obtained using a dose of 30 mg/kg per day of 2-iminobiotin. Levels of HSP70 were increased in the ipsilateral hemisphere in both groups ( P<0.05), but the increase was significantly ( P<0.05) less in the rats receiving the optimal dose of 2-iminobiotin (30 mg/kg per day). Hypoxia-ischemia did not lead to increased levels of nitrotyrosine, nor did 2-iminobiotin influence levels of nitrotyrosine. In contrast, hypoxia-ischemia induced an increase in cytochrome c level that was prevented by 2-iminobiotin. In conclusion, 2-iminobiotin administered after hypoxia-ischemia provides long-term neuroprotection. This neuroprotection is obtained by mechanisms other than a reduction of nitrotyrosine formation in proteins.