bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of sensory nerves in vasodilator responses to acetylcholine and potassium ions in rat hepatic artery
Authors: Högestätt Edward D , Johansson Rebecka , Andersson David A , Zygmunt Peter M 
Published: January 2005

In the presence of ouabain (1 mM), acetylcholine and KCl (5 mM) evoked endothelium‐independent relaxations in rat hepatic arteries. Treatment with capsaicin (10 μM), scopolamine (1 μM) or CGRP8–37 (3 μM) prevented these relaxations. Acetylcholine‐induced relaxations in intact arterial segments in the presence of indomethacin (10 μM) and NG‐nitro‐L‐arginine (0.3 mM) were only partially inhibited by ouabain plus BaCl2 (30 μM). However, ouabain plus BaCl2 almost abolished such relaxations in capsaicin‐pre‐treated preparations. In arteries without endothelium, the neurosecretagogue α‐latrotoxin (1 nM) induced complete relaxations, which were abolished by CGRP8–37 or pre‐treatment with capsaicin. α‐Latrotoxin also induced a smooth muscle hyperpolarization (12±2 mV), which was abolished by CGRP8–37. The ability of ouabain to disclose a CGRP‐mediated neurogenic relaxation must be considered when this agent is used as a pharmacological tool. The results further suggest that CGRP is a nerve‐derived hyperpolarizing factor in the rat hepatic artery.British Journal of Pharmacology (2000) 130, 27–32; doi:10.1038/sj.bjp.0703258
Selective block of late Na+ current by local anaesthetics in rat large sensory neurones
Authors: Baker Mark D 
Published: January 2005

The actions of lignocaine and benzocaine on transient and late Na+ current generated by large diameter (50 μm) adult rat dorsal root ganglion neurones, were studied using patch‐clamp techniques.
Both drugs blocked whole‐cell late Na+ current in a concentration‐dependent manner. At 200 ms following the onset of a clamp step from −110 to −40 mV, the apparent K for block of late Na+ current by lignocaine was 57.8±15 μM (mean±s.e.mean, n=4). The value for benzocaine was 24.9±3.3 μM, (mean±s.e.mean, n=3).
The effect of lignocaine on transient current, in randomly selected neurones, appeared variable (n=8, half‐block from ∼50 to 400 μM). Half‐block by benzocaine was not attained, but both whole‐cell (n=11) and patch data suggested a high apparent K,>250 μM. Transient current always remained after late current was blocked.
The voltage‐dependence of residual late current steady‐state inactivation was not shifted by 20 μM benzocaine (n=3), whereas 200 μM benzocaine shifted the voltage‐dependence of transient current steady‐state inactivation by −18.7±5.9 mV (mean±s.e.mean, n=4).
In current‐clamp, benzocaine (250 μM) could block subthreshold, voltage‐dependent inward current, increasing the threshold for eliciting action potentials, without preventing their generation (n=2).
Block of late Na+ current by systemic local anaesthetic may play a part in preventing ectopic impulse generation in sensory neurones.

British Journal of Pharmacology (2000) 129, 1617–1626; doi:10.1038/sj.bjp.0703261
Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil
Authors: Izzo Angelo A , Pinto Luisa , Borrelli Francesca , Capasso Raffaele , Mascolo Nicola , Capasso Francesco 
Published: January 2005

We have evaluated the effect of cannabinoid drugs, administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.) on upper gastrointestinal transit in control and in croton oil‐treated mice.
The cannabinoid agonists, WIN 55,212‐2 (2–239 nmol mouse−1) and cannabinol (24–4027 nmol mouse−1), decreased while the CB1 antagonist SR141716A (2–539 nmol mouse−1) increased transit in control mice. WIN 55,212‐2, cannabinol and SR141716A had lower ED50 values when administered i.c.v., than when administered i.p. The CB2 antagonist SR144528 (52 nmol mouse−1, i.p.) was without effect.
During croton oil (0.01 ml mouse−1, p.o.)‐induced diarrhoea, the ED50 values of i.p.‐injected WIN 55,212‐2 and cannabinol (but not SR141716A) were significantly decreased (compared to control mice). However, the ED50 values of WIN 55,212‐2 were similar after i.p. or i.c.v. administration.
The inhibitory effects of WIN 55,212‐2 and cannabinol were counteracted by SR141716A (16 nmol mouse−1, i.p.) but not by SR144528 (52 nmol mouse−1, i.p.) both in control and croton‐oil treated mice.
Ganglionic blockade with hexamethonium (69 nmol mouse−1, i.p.) did not modify the inhibitory effect of i.p.‐injected cannabinoid agonists either in control or in croton‐oil treated mice.
The lower ED50 values of cannabinoid drugs after i.c.v. administration suggest a central (CB1) site of action. However, a peripheral site of action is suggested by the lack of effect of hexamethonium. In addition, croton oil‐induced diarrhoea enhances the effect of cannabinoid agonists by a peripheral mechanism.

British Journal of Pharmacology (2000) 129, 1627–1632; doi:10.1038/sj.bjp.0703265
Loss of muscarinic antinociception by antisense inhibition of M1 receptors
Authors: Ghelardini Carla , Galeotti Nicoletta , Bartolini Alessandro 
Published: January 2005

The effect on cholinergic analgesia of inactivation of the M1 gene by an antisense oligodeoxyribonucleotide (aODN) was investigated in the mouse hot plate test. Mice received a single intracerebroventricular (i.c.v.) injection of anti‐M1 aODN (0.3, 1.0 or 2.0 nmol per injection), degenerate ODN (dODN) or vehicle on days 1, 4 and 7.
A dose‐dependent inhibition of the antinociception induced by the muscarinic agonists oxotremorine (0.1 mg kg−1 s.c.) and McN‐A‐343 (30 μg per mouse i.c.v.) and the cholinesterase inhibitor physostigmine (0.2 mg kg−1 s.c.) was observed 24 h after the last i.c.v. injection of aODN. Time‐course experiments revealed that, after the end of the aODN treatment, sensitivity to analgesic drugs progressively appeared reaching the normal range at 96 h.
The anti‐M1 aODN was selective against muscarinic antinociception since the enhancement of pain threshold produced by morphine and baclofen were not affected by the above‐mentioned treatment. dODN, used as control, did not affect muscarinic antinociception.
Binding studies evidenced a selective reduction of M1 receptor levels in the hippocampus of aODN‐treated mice.
Neither aODN, dODN nor vehicle produced any behavioural impairment of mice as revealed by the rota‐rod and Animex experiments.
These results indicate that activation of M1 muscarinic receptor subtype is fundamental to induce central cholinergic analgesia in mice.

British Journal of Pharmacology (2000) 129, 1633–1640; doi:10.1038/sj.bjp.0703268
Glucocorticoids act within minutes to inhibit recruitment of signalling factors to activated EGF receptors through a receptor‐dependent, transcription‐independent mechanism
Authors: Croxtall Jamie D , Choudhury Qam , Flower Rod J 
Published: January 2005

Recruitment to activated tyrosine kinase growth factor receptors of Grb2 and p21ras leads to downstream activation of the kinases Raf, MAPK/Erk kinase (Mek) and, subsequently, extracellular signal‐regulated kinase (Erk). Activated Erk phosphorylates specific serine residues within cytosolic phospholipase A2 (PLA2), promoting enzyme translocation to membranes and facilitating liberation of arachidonic acid (AA).
In the A549 human adenocarcinoma cell line dexamethasone inhibited epidermal growth factor (EGF)‐stimulated cytosolic PLA2 (cPLA2) activation and AA release by blocking the recruitment of Grb2 to the activated EGF receptor (EGF‐R) through a glucocorticoid receptor (GR)‐dependent (RU486‐sensitive), transcription‐independent (actinomycin‐insensitive), mechanism.
The dexamethasone‐induced block of Grb2 recruitment was parallelled by changes in phosphorylation status and subcellular localization of lipocortin 1 (LC1) and an increase in the amount of the tyrosine phosphoprotein co‐localized with EGF‐R.
Like dexamethasone, peptides containing E‐Q‐E‐Y‐V from the N‐terminal domain of LC1 also blocked ligand‐induced association of Grb2, p21ras and Raf.
Our results point to an unsuspected rapid effect of glucocorticoids, mediated by occupation of GR but not by changes in gene transcription, which is brought about by competition between LC1 and Grb2 leading to a failure of recruitment off signalling factors to EGF‐R

British Journal of Pharmacology (2000) 130, 289–298; doi:10.1038/sj.bjp.0703272
Induction of skeletal muscle contracture and calcium release from isolated sarcoplasmic reticulum vesicles by sanguinarine
Authors: Hu C M , Cheng H W , Cheng Y W , Kang J J 
Published: January 2005

The benzophenanthrine alkaloid, sanguinarine, was studied for its effects on isolated mouse phrenic‐nerve diaphragm preparations. Sanguinarine induced direct, dose‐dependent effects on muscle contractility.
Sanguinarine‐induced contracture was partially inhibited when the extracellular Ca2+ was removed or when the diaphragm was pretreated with nifedipine. Depletion of sarcoplasmic reticulum (SR) internal calcium stores completely blocked the contracture.
Sanguinarine induced Ca2+ release from the actively loaded SR vesicles was blocked by ruthenium red and dithiothreitol (DTT), consistent with the ryanodine receptor (RyR) as the site of sanguinarine action.
Sanguinarine altered [3H]‐ryanodine binding to the RyR of isolated SR vesicles, potentiating [3H]‐ryanodine binding at lower concentrations and inhibiting binding at higher concentrations. All of these effects were reversed by DTT, suggesting that sanguinarine‐induced Ca2+ release from SR occurs through oxidation of critical SH groups of the RyR SR calcium release channel.

British Journal of Pharmacology (2000) 130, 299–306; doi:10.1038/sj.bjp.0703279
Correlation of leukocyte adhesiveness, adhesion molecule expression and leukocyte‐induced contraction following balloon angioplasty
Authors: Kennedy Simon , McPhaden Allan R , Wadsworth Roger M , Wainwright Cherry L 
Published: January 2005

The aim of this study was to examine the changes in leukocyte adhesion and leukocyte‐induced contraction in balloon‐injured rabbit subclavian artery and to correlate these changes with vessel morphology and expression of adhesion molecules on the injured arteries.
Rabbits were anaesthetized and their left subclavian arteries were injured by balloon inflation and withdrawal followed by sacrifice at 2, 24, 48 h or 8 days after injury. The left and right subclavian arteries were removed and leukocytes were isolated from autologous rabbit blood. Leukocyte‐induced contraction was measured in 5‐HT precontracted artery rings and leukocyte adhesion was measured using 51Cr‐labelled leukocytes. Immunocytochemistry using paraffin‐embedded tissue was employed to detect changes in the expression of adhesion molecules on injured arteries.
Autologous leukocytes caused a contraction of rabbit subclavian artery rings, which was prevented by L‐NAME (10−3 M). Balloon‐induced injury abolished the contractile response to leukocytes, which correlated with loss of carbachol‐induced relaxation
Balloon injury markedly enhanced the adhesiveness of the subclavian artery for leukocytes, most notably at 24 and 48 h after injury (1.7 and 1.8 fold respectively). Increased leukocyte adhesion at these two time points correlated with an upregulation of E‐selectin, P‐selectin and VCAM‐1 expression on the remaining endothelium of the injured artery.
Vessel morphology revealed that balloon inflation had induced an infiltration of inflammatory cells into the vessel wall, the greatest increase being seen at 24 h after injury.
It is concluded that an increase in the expression of E‐selectin, P‐selectin and VCAM‐1 following balloon‐induced injury leads to enhanced leukocyte adhesion and migration into the injured vessel.

British Journal of Pharmacology (2000) 130, 95–103; doi:10.1038/sj.bjp.0703282
Cisplatin‐induced early and delayed emesis in the pigeon
Authors: Tanihata Sachiko , Igarashi Hiroaki , Suzuki Masami , Uchiyama Toshimitsu 
Published: January 2005

Intravenously injected cisplatin at a dose of 4 mg kg−1 induced early and delayed emesis in all pigeons without occurrence of lethality during a 72 h observation period. The early emetic response occurred with a latency of 81.3±8.0 min (n=15) and reached a peak at 2–3 h, and decreased gradually within 8 h after injection. Then the delayed emetic response, whose peak was found between 10 to 23 h, lasted up to 48 h. The emetic response markedly declined after 48 h.
Reserpine markedly reduced monoamine levels in both brain and intestine and completely abolished the early and delayed emesis. Dexamethasone markedly reduced not only the early but also the delayed emetic responses. p‐Chlorophenylalanine decreased the level of serotonin in brain and intestine without affecting noradrenaline and dopamine and partly reduced the early emetic response, but did not affect delayed emesis.
Bilateral vagotomy prolonged the latency time to the onset of early emesis, and reduced the emetic responses in both the early and delayed phases.
The above results suggest that the cisplatin‐induced early emesis in the pigeon is partially mediated via the vagal nerve and reserpine‐sensitive monoaminergic systems including the serotonergic system; the delayed emesis is associated with monoaminergic but not the serotonergic systems.

British Journal of Pharmacology (2000) 130, 132–138; doi:10.1038/sj.bjp.0703283
Non‐NF‐κB elements are required for full induction of the rat type II nitric oxide synthase in vascular smooth muscle cells
Authors: Zhang Hanfang , Teng Xingwu , Snead Connie , Catravas John D 
Published: January 2005

We have investigated the role of the NF‐κB binding sites and other promoter elements beyond NF‐κB in iNOS induction in rat vascular smooth muscle cells (SMC).
Rat aortic SMC transfected with iNOS promoter constructs with either mutation or deletion of the downstream NF‐κB site exhibited about 50% reduction in promoter activity in response to a cytokine mixture, whereas either mutation or deletion of the upstream NF‐κB site reduced promoter activity by 90%, suggesting that the latter site is the most important, and that co‐existence of two NF‐κB sites is necessary for iNOS induction.
Nuclear NF‐κB activity was robustly induced by TNF‐α. However, TNF‐α alone did not induce iNOS promoter activity, protein expression, or nitrite production, indicating that NF‐κB activation alone is not sufficient for iNOS induction.
The construct up to −890 bp, containing the downstream NF‐κB site, exhibited little response to cytokines. The construct up to −1.0 kb, containing the two NF‐κB sites exhibited only 22% of full promoter activity. The regions −1001 to −1368 bp and −2 to −2.5 kb contributed an additional 43 and 22% promoter activity, respectively.
Internal deletion or reversal of the orientation of −1001 to −1368 bp in the full promoter resulted in 40% reduction in promoter activity.
These data suggest that the co‐existence of two NF‐κB sites is essential for core promoter activity, but that full induction of the rat SMC iNOS gene requires other elements located between −1.0 to −1.37 and −2.0 to −2.5 kb of the promoter.

British Journal of Pharmacology (2000) 130, 270–278; doi:10.1038/sj.bjp.0703284
Ecto‐nucleotide pyrophosphatase modulates the purinoceptor‐mediated signal transduction and is inhibited by purinoceptor antagonists
Authors: Grobben Bert , Claes Patrik , Roymans Dirk , Esmans Edgard L , Van Onckelen Harry , Slegers Herman 
Published: January 2005

The effect of ecto‐nucleotide pyrophosphatase (ecto‐NPPase; EC 3.6.1.9) on the ATP‐ and ADP‐mediated receptor activation was studied in rat C6 glioma cells. The P2‐purinoceptor antagonists pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) and reactive blue (RB2) are potent inhibitors (IC50=12±3 μM) of the latter enzyme. 4,4′‐diisothiocyanatostilbene‐2,2′ disulfonic acid (DIDS), 5′‐phosphoadenosine 3′‐phosphate (PAP) and suramin were less potent inhibitors with an IC50 of 22±4, 36±7 and 72±11 μM respectively.
P1‐purinoceptor antagonists CGS 15943, cyclo‐pentyl theophylline (CTP) and theophylline did not affect the activity of the ecto‐NPPase.
ATP‐ and ADP‐mediated P2Y1‐like receptor activation inhibited the (−)‐isoproterenol‐induced increase of intracellular cyclic AMP concentration. PPADS, an ineffective P2Y‐antagonist in C6, potentiated the ATP and ADP effect approximately 3 fold due to inhibition of nucleotide hydrolysis by the ecto‐NPPase.
We conclude that ecto‐NPPase has a modulatory effect on purinoceptor‐mediated signalling in C6 glioma cell cultures.

British Journal of Pharmacology (2000) 130, 139–145; doi:10.1038/sj.bjp.0703289
Role of L‐arginine in the vascular actions and development of tolerance to nitroglycerin
Authors: Abou‐Mohamed Gamal , Kaesemeyer Wayne H , Caldwell Ruth B , Caldwell Robert W 
Published: January 2005

The goal of this work was to test the role of nitric oxide synthase (NOS) and its substrate L‐arginine in development of tolerance to nitroglycerin's (GTN) vasodilator actions.
GTN's effects on NOS activity and NO formation were tested in cultured bovine aortic endothelial cells (BAECs). The arginine to citrulline conversion assay showed that GTN stimulated NOS basal activity in BAECs by ∼40%, comparable with acetylcholine (ACh)‐treated controls. Both effects were blocked by L‐NMMA. Photometric assays showed that both GTN and ACh‐stimulated NO formation. Both effects were potentiated by L‐arginine and inhibited by L‐NAME. L‐NAME inhibited ACh responses ∼80% compared with ∼40% for GTN responses.
The aortic ring assay showed that 2 h pretreatment with GTN caused substantial tolerance to GTN's vasodilating effects as evidenced by a 38 fold rightward shift of the concentration‐relaxation curve. In contrast to D‐arginine, addition of L‐arginine substantially inhibited this effect, reducing the rightward shift to 4.4 fold of control values. GTN tolerance was associated with a 40% reduction in L‐arginine tissue levels. GTN had a biphasic effect on BAEC uptake of L‐arginine, stimulating uptake at 5 and 15 min, and suppressing uptake after 1 and 4 h
In summary, acute GTN treatment stimulates endothelial NOS activity in producing NO and increases cellular uptake of L‐arginine. Prolonged GTN exposure reduces GTN's vasodilator actions, decreases L‐arginine tissue levels and depresses BAECs uptake of L‐arginine. Supplementation of L‐arginine reduces development of GTN tolerance. These data indicate that GTN tolerance depends in part on activation of the NOS pathway.

British Journal of Pharmacology (2000) 130, 211–218; doi:10.1038/sj.bjp.0703293
Activation of I2‐imidazoline receptors enhances supraspinal morphine analgesia in mice: a model to detect agonist and antagonist activities at these receptors
Authors: Sánchez‐Blázquez Pilar , Boronat M Assumpció , Olmos Gabriel , García‐Sevilla Jesús A , Garzón Javier 
Published: January 2005

This work investigates the receptor acted upon by imidazoline compounds in the modulation of morphine analgesia. The effects of highly selective imidazoline ligands on the supraspinal antinociception induced by morphine in mice were determined.
Intracerebroventricular (i.c.v.) or subcutaneous (s.c.) administration of ligands selective for the I2‐imidazoline receptor, 2‐BFI, LSL 60101, LSL 61122 and aganodine, and the non selective ligand agmatine, increased morphine antinociception in a dose‐dependent manner. Neither moxonidine, a mixed I1‐imidazoline and α2‐adrenoceptor agonist, RX821002, a potent α2‐adrenoceptor antagonist that displays low affinity at I2‐imidazoline receptors, nor the selective non‐imidazoline α2‐adrenoceptor antagonist RS‐15385‐197, modified the analgesic responses to morphine.
Administration of pertussis toxin (0.25 μg per mouse, i.c.v.) 6 days before the analgesic test blocked the ability of the I2‐imidazoline ligands to potentiate morphine antinociception.
The increased effect of morphine induced by I2‐imidazoline ligands (agonists) was completely reversed by idazoxan and BU 224. Identical results were obtained with IBI, which alkylates I2‐imidazoline binding sites. Thus, both agonist and antagonist properties of imidazoline ligands at the I2‐imidazoline receptors were observed.
Pre‐treatment (30 min) with deprenyl, an irreversible inhibitor of monoamine oxidase B (IMAO‐B), produced an increase of morphine antinociception. Clorgyline, an irreversible IMAO‐A, given 30 min before morphine did not alter the effect of the opioid. At longer intervals (24 h) a single dose of either clorgyline or deprenyl reduced the density of I2‐imidazoline receptors and prevented the I2‐mediated potentiation of morphine analgesia.
These results demonstrate functional interaction between I2‐imidazoline and opioid receptors. The involvement of Gi‐Go transducer proteins in this modulatory effect is also suggested.

British Journal of Pharmacology (2000) 130, 146–152; doi:10.1038/sj.bjp.0703294
Role of uptake inhibition and autoreceptor activation in the control of 5‐HT release in the frontal cortex and dorsal hippocampus of the rat
Authors: Hervás Ildefonso , Queiroz Claudio M T , Adell Albert , Artigas Francesc 
Published: January 2005

Using brain microdialysis, we compared the relative role of 5‐hydroxytryptamine (5‐HT; serotonin) blockade and somatodendritic 5‐HT1A and/or terminal 5‐HT1B autoreceptor activation in the control of 5‐HT output.
Fluoxetine (10 mg kg−1 i.p.) doubled the 5‐HT output in frontal cortex and dorsal hippocampus. The 5‐HT1A receptor antagonist WAY 100635, (0.3 mg kg−1 s.c.) potentiated the effect of fluoxetine only in frontal cortex (to ∼500 % of baseline).
Methiothepin (10 mg kg−1 s.c.) further enhanced the 5‐HT rise induced by fluoxetine+WAY 100635, to 835±179% in frontal cortex and 456±24% in dorsal hippocampus. Locally applied, methiothepin potentiated the fluoxetine‐induced 5‐HT rise more in the former area.
The selective 5‐HT1B receptor antagonist SB‐224289 (4 mg kg−1 i.p.) enhanced the effect of fluoxetine (10 mg kg−1 i.p.) in both areas. As with methiothepin, SB‐224289 (4 mg kg−1 i.p.) further enhanced the 5‐HT increase produced by fluoxetine+WAY 100635 more in frontal cortex (613±134%) than in dorsal hippocampus (353±59%).
Locally applied, fluoxetine (10–300 μM; EC50=28–29 μM) and citalopram (1–30 μM; EC50=1.0–1.4 μM) increased the 5‐HT output two to three times more in frontal cortex than in dorsal hippocampus.
These data suggest that the comparable 5‐HT increase produced by systemic fluoxetine in frontal cortex and dorsal hippocampus results from a greater effect of reuptake blockade in frontal cortex that is offset by a greater autoreceptor‐mediated inhibition of 5‐HT release. As a result, 5‐HT autoreceptor antagonists preferentially potentiate the effect of fluoxetine in frontal cortex.

British Journal of Pharmacology (2000) 130, 160–166; doi:10.1038/sj.bjp.0703297