bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nerve‐induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis
Authors: Iversen Henrik H. , Celsing Fredrik , Leone Anna M. , Gustafsson Lars E. , Wiklund N. Peter 
Published: August 2006

Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve‐induced NO formation in vivo in the gastrointestinal tract.
Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis.
During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor Nω‐nitro‐L‐arginine methyl ester (l‐NAME 30 mg kg−1). Furthermore, L‐NAME significantly increased nerve‐induced gastric and colonic contractions, as well as spontaneous colonic contractions.
In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.
Cellular localization of the inhibitory action of abruquinone A against respiratory burst in rat neutrophils
Authors: Hsu Mei F , Raung Shue L , Tsao Lo T , Kuo Sheng C , Wang Jih P 
Published: August 2006

The possible mechanisms of action of the inhibitory effect of abruquinone A on the respiratory burst in rat neutrophils in vitro was investigated.
Abruquinone A caused an irreversible and a concentration‐dependent inhibition of formylmethionyl‐leucyl‐phenylalanine (fMLP) plus dihydrocytochalasin B (CB)‐ and phorbol 12‐myristate 13‐acetate (PMA)‐induced superoxide anion (O2.−) generation with IC50 values of 0.33±0.05 μg ml−1 and 0.49±0.04 μg ml−1, respectively.
Abruquinone A also inhibited O2 consumption in neutrophils in response to fMLP/CB and PMA. However, abruquinone A did not scavenge the generated O2.− in xanthine‐xanthine oxidase system and during dihydroxyfumaric acid (DHF) autoxidation.
Abruquinone A inhibited both the transient elevation of [Ca2+]i in the absence of [Ca2+]o (IC50 7.8±0.2 μg ml−1) and the generation of inositol trisphosphate (IP3) (IC50 10.6±2.0 μg ml−1) in response to fMLP.
Abruquinone A did not affect the enzyme activities of neutrophil cytosolic protein kinase C (PKC) and porcine heart protein kinase A (PKA).
Abruquinone A had no effect on intracellular guanosine 3′: 5′‐cyclic monophosphate (cyclic GMP) levels but decreased the adenosine 3′: 5′‐cyclic monophosphate (cyclic AMP) levels.
The cellular formation of phosphatidic acid (PA) and phosphatidylethanol (PEt) induced by fMLP/CB was inhibited by abruquinone A with IC50 values of 2.2±0.6 μg ml−1 and 2.5±0.3 μg ml−1, respectively. Abruquinone A did not inhibit the fMLP/CB‐induced protein tyrosine phosphorylation but induced additional phosphotyrosine accumulation on proteins of 73–78 kDa in activated neutrophils.
Abruquinone A inhibited both the O2.− generation in PMA‐activated neutrophil particulate NADPH oxidase (IC50 0.6±0.1 μg ml−1) and the iodonitrotetrazolium violet (INT) reduction in arachidonic acid (AA)‐activated cell‐free system (IC50 1.5±0.2 μg ml−1).
Collectively, these results indicate that the inhibition of respiratory burst in rat neutrophils by abruquinone A is mediated partly by the blockade of phospholipase C (PLC) and phospholipase D (PLD) pathways, and by suppressing the function of NADPH oxidase through the interruption of electron transport.

British Journal of Pharmacology (1997) 120, 917–925; doi:10.1038/sj.bjp.0700974
Effect of non‐toxic mercury, zinc or cadmium pretreatment on the capacity of human monocytes to undergo lipopolysaccharide‐induced activation
Authors: Koropatnick J , Zalups R K 
Published: August 2006

Metal salts can inhibit cell activity through direct toxicity to critical cellular molecules and structures. On the other hand, they can also change cell behaviour by inducing specific genes (including genes encoding members of the metallothionein [MT] gene family). Therefore, transition metals may affect cell functions either by acting as a toxin, or by transmitting or influencing signals controlling gene expression.
To explore the latter possibility, we measured the ability of low, non‐toxic metal pretreatment to alter immune cell behaviour. We previously found that pretreatment of human monocytes with zinc induces metallothionein gene expression and alters their capacity to undergo a bacterial lipopolysaccharide‐induced respiratory burst. We showed here that cadmium and mercury salts, at concentrations that exert no discernible toxicity, inhibit activation of human monocytic leukemia (THP‐1) cells. CdCl2 1 μm, ZnCl2 20–40 μm or HgCl2 2 μm pretreatment for 20 h induced MT‐2 mRNA and total MT protein accumulation and had no effect on proliferation potential or metabolic activity, but significantly inhibited the ability of subsequent lipopolysaccharide treatment to induce the oxidative burst, increased adhesion to plastic, and MT‐2 and interleukin‐1β (IL‐1β) mRNA accumulation.
The phenomenon of metal‐induced suppression of monocyte activation, at metal concentrations that have no effect on cell viability, has important implications for assessment of acceptable levels of human exposure to cadmium, zinc and mercury.

British Journal of Pharmacology (1997) 120, 797–806; doi:10.1038/sj.bjp.0700975
Differential regulation by protein kinase C isoforms of nitric oxide synthase induction in RAW 264.7 macrophages and rat aortic smooth muscle cells
Authors: Paul Andrew , Doherty Kirsten , Plevin Robin 
Published: August 2006

In RAW 264.7 murine macrophages and rat aortic smooth muscle (RASM) cells lipopolysaccharide (LPS) alone or in combination with interferon γ (IFNγ) or forskolin, respectively, stimulated the expression of the 130 kDa inducible isoform of nitric oxide synthase (iNOS) in both a time‐ and concentration‐dependent manner.
Incubation with the direct activator of protein kinase C (PKC), phorbol 12‐myristate 13‐acetate (PMA) alone, did not result in detectable iNOS expression in either cell type.
Chronic PMA pretreatment resulted in significant down‐regulation of α, β and ε isoforms of PKC in RAW 264.7 macrophages and corresponded to a 20–30% reduction in LPS‐induced iNOS expression. In contrast, IFNγ alone or in combination with LPS stimulated an approximate 20% and 50% potentiation, respectively.
Pre‐incubation with PKC inhibitors (calphostin C and H‐7) showed similar effects upon stimulated induction of iNOS.
In RASM cells chronic PMA pretreatment resulted in down‐regulation of α and ε PKC isoforms and corresponded to potentiation of iNOS expression in response to LPS alone or in combination with forskolin.
Co‐incubation of RASM cells in the presence of PMA, angiotensin II (AII) or foetal calf serum (FCS) resulted in the inhibition of iNOS expression in response to LPS alone or in combination with forskolin.
Differential sensitivity to PKC inhibitors (calphostin C and H‐7) was observed in RASM cells and exhibited both negative and positive modulation of stimulated induction.
In addition the PKC inhibitor compound Ro‐31–8220 abolished stimulated induction in both cell types in response to all treatments.
These results suggest that PKC activation is required for induction of the 130 kDa isoform of NOS in both RAW 264.7 macrophages and RASM cells. However, individual PKC isoforms regulate iNOS expression in both a positive and negative manner.

British Journal of Pharmacology (1997) 120, 940–946; doi:10.1038/sj.bjp.0700976
Renal adenosine A1 receptor binding characteristics and mRNA levels during the development of acute renal failure in the rat
Authors: Gould J , Morton M J , Sivaprasadarao A , Bowmer C J , Yates M S 
Published: August 2006

The binding characteristics and mRNA levels for renal adenosine A1 receptors were investigated in normal rats and rats with acute renal failure (ARF) induced by either glycerol or HgCl2.
Saturation isotherms determined from the binding of [3H]‐1,3‐dipropyl‐8‐cyclopentylxanthine ([3H]‐DPCPX), a selective adenosine A1 antagonist, to renal membranes of untreated rats gave values of 0.62 nm for the equilibrium dissociation constant (Kd) and 19.9 fmol mg−1 protein for the density of binding sites (Bmax). No saturable binding was observed with [3H]‐2‐(p‐(carboxylethyl)‐phenylethylamino)‐5′‐N‐ethylcarboxamido adenosine ([3H]‐CGS 21680), a selective adenosine A2a agonist.
By contrast to time‐matched controls, renal membranes obtained from rats 16 and 48 h following the induction of ARF with glycerol, showed statistically significant increases (2–4 fold) in both Bmax and Kd for the binding of [3H]‐DPCPX. No significant changes in the binding characteristics of [3H]‐DPCPX were noted with membranes from rats 48 h following the production of ARF with HgCl2.
Adenosine A1 receptor mRNA levels were significantly elevated 0.5, 16 and 48 h following induction of ARF with glycerol, whilst no change was noted in mRNA levels for β‐actin at the same time points. No statistically significant changes in adenosine A1 receptor or β‐actin mRNA levels were noted 48 h after the induction of ARF with HgCl2.
This study indicates that glycerol‐induced ARF in the rat is associated with an increase in renal adenosine A1 receptor density which appears to result from increased transcription of the gene for this receptor. An increase in adenosine A1 receptor density in renal resistance vessels may explain, at least in part, the enhanced renal vasoconstrictor response to adenosine in glycerol‐induced ARF that was noted in a previous study.

British Journal of Pharmacology (1997) 120, 947–953; doi:10.1038/sj.bjp.0700980
Inhibition of [3H]‐U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart
Authors: Zhang Wei‐Min , Wang Hong‐Xin , Xia Qiang , Wong Tak‐Ming 
Published: August 2006

The calcium channel blockers (CCBs), nifedipine, nicardipine, diltiazem and verapamil, were used to displace the binding of [3H]‐U69593 ((5a,7a,8b)‐(+)‐N‐methyl‐N‐(7‐[1‐pyrrolidinyl]‐1‐oxaspiro[4,5]dec‐8‐yl)‐benzeneacetamide), a specific κ‐opioid agonist, in the rat cardiac sarcolemma. The CCBs competed with the binding of [3H]‐U69593 (4 nm) in a dose‐dependent manner. The displacing potency of verapamil was 55 times greater than that of nifedipine.
The effects of two CCBs, verapamil and nifedipine, on the arrhythmogenic action of κ‐receptor stimulation by a specific κ‐receptor agonist, U50,488H (trans‐(±‐3,4‐dichloro‐N‐methyl‐N‐(2‐[1‐pyrrolidinyl] cyclohexyl) benzeacetamide methanesulphonate), were also studied in the rat isolated perfused heart. U50,488H 80–800 nmol dose‐dependently induced arrhythmias, which were completely abolished by a selective κ‐receptor antagonist, nor‐BNI (nor‐binaltorphimine,17,17′‐(dicyclopropylmethyl)‐6,6′,7,7′‐6,6′‐imino‐7,7′‐binorphinan‐3,4′,14, 14′‐tetrol), at 100 nmol. The arrhythmogenic effect was also attenuated by both verapamil and nifedipine in a dose‐dependent manner. The ED50 values for verapamil and nifedipine were 2.75 and 63.7 nmol, respectively. The antiarrhythmic potencies of these two CCBs were correlated to their displacing potencies and inversely related to their well known potencies in inhibiting transmembrane Ca2+ influx in the cardiac muscle.
Measurement of [Ca2+]i in the absence of free extracellular Ca2+ by a spectrofluorometric method, with fura‐2 as Ca2+ indicator, showed that U50,488H 5×10−5 m slowly increased [Ca2+]i in single ventricular myocytes and this effect was abolished by pretreatment with nor‐BNI (5 μm), or ryanodine (5 μm). Verapamil 1 and 10 μm abolished the effect of U50,488H in 37.5% (3 out of 8) and 100% (12 out of 12) of the cells studied, respectively. On the other hand, nifedipine 10 and 100 μm had no effect at all. Neither verapamil nor nifedipine exerted any significant effect on the caffeine‐induced Ca2+ transient.
The observations suggest that CCBs may inhibit the actions of κ‐receptor stimulation at the level of the κ‐receptor.

British Journal of Pharmacology (1997) 120, 827–832; doi:10.1038/sj.bjp.0700985
Nitric oxide modulation of transcellular biosynthesis of cys‐leukotrienes in rabbit leukocyte‐perfused heart
Authors: Buccellati Carola , Rossoni Giuseppe , Bonazzi Albino , Berti Ferruccio , Maclouf Jacques , Folco Giancarlo , Sala Angelo 
Published: August 2006

We have studied the role of nitric oxide (NO) in the regulation of the transcellular biosynthesis of sulphidopeptide leukotrienes (cys‐LT) generated upon neutrophil‐vascular wall interactions and their functional consequences, in the spontaneously beating, cell‐perfused, heart of the rabbit.
Hearts were perfused under recirculating conditions (50 ml) with 5×106 purified human neutrophils (PMNL), and challenged with 0.5 μm A‐23187 for 30 min. Coronary perfusion pressure (CPP) and left‐ventricular end‐diastolic pressure (LVEDP) were monitored. Cys‐LT formation was measured by reversed phase high performance liquid chromatography (h.p.l.c.) and u.v. spectral analysis. Myeloperoxidase (MPO) enzyme activity, assayed in aliquots of the recirculating buffer, was used as a marker of PMNL adhesion to the coronary endothelium.
Basal CPP and LVEDP values averaged 45±1.4 mmHg and 5±0.1 mmHg, respectively; A‐23187 triggered an increase in CPP (134±9 mmHg, at 30 min) which was significantly attenuated by pretreatment with l‐arginine, 100 μm (90±3 mmHg, at 30 min). Pretreatment with NG‐monomethyl‐l‐arginine, 10 μm (l‐NMMA), induced a marked increase in CPP (290±40 mmHg, at 20 min) and in LVEDP (47±16 mmHg), so pronounced that it caused cardiac arrest in systole in 5 out of 6 hearts and these were prevented by l‐arginine, 100 μm (CPP 115±10 mmHg, LVEDP 6±1.1 mmHg, at 30 min).
The increase in CPP was accompanied by the release of cys‐LT in the circulating buffer, which was reduced significantly by l‐arginine. Pretreatment with l‐NMMA, caused a marked rise in cys‐LT concentrations which was prevented by l‐arginine.
Neither l‐arginine nor l‐NMMA affected directly the A‐23187‐induced arachidonic acid (AA) metabolism in isolated PMNL alone.
Pretreatment with l‐NMMA caused a prompt drop in myeloperoxidase (MPO) activity, suggesting rapid adhesion of PMNL to the coronary wall; this effect was significantly blunted by l‐arginine.
This study suggests that NO provides cardioprotection in an organ model of transcellular metabolism of cys‐LT by preventing PMNL adhesion to the coronary intima.

British Journal of Pharmacology (1997) 120, 1128–1134; doi:10.1038/sj.bjp.0700994
Differential influence of D1 and D2 dopamine receptors on acute opiate withdrawal in guinea‐pig isolated ileum
Authors: Capasso A , Sorrentino L 
Published: August 2006

The effects exerted by D1 and D2 dopamine agonists and antagonists on the acute opiate withdrawal induced by μ‐ and κ‐receptor agonists were investigated in vitro.
Following a 4 min in vitro exposure to morphine (moderately selective μ‐agonist), [d‐Ala2, Me‐Phe4, Gly‐ol5]enkephalin (DAMGO, highly selective μ‐agonist) or U‐50488H (highly selective κ‐agonist) the guinea‐pig isolated ileum exhibited a strong contracture after the addition of naloxone.
The non‐selective dopamine receptor antagonist haloperidol when added before or after the opioid agonists, was able dose‐dependently to prevent or to reverse the naloxone‐induced contracture after exposure to μ‐ (morphine and DAMGO) and κ‐ (U‐50488H) opioid agonists. The non‐selective dopamine receptor agonist, apomorphine, was able to exert the same effects only at the highest concentration used.
The selective D2 dopamine receptor antagonist, sulpiride, was also able to reduce dose‐dependently both μ‐ and κ‐opioid withdrawal, whereas the D1‐receptor selective antagonist SCH 23390 did not affect either μ‐ or κ‐opioid withdrawal.
Bromocriptine, a D2 selective dopamine receptor agonist was able to increase significantly, and in a concentration‐dependent manner, the naloxone‐induced contracture by μ‐ and κ‐opioid agonists, whereas SKF 38393, a D1 selective dopamine receptor agonist, increased only the withdrawal after morphine or U50‐488H.
Our data indicate that both D1 and D2 dopamine agonists and antagonists are able to influence opiate withdrawal in vitro, suggesting an important functional interaction between the dopaminergic system and opioid withdrawal at both the μ‐ and κ‐receptor level.
Furthermore, the ability of sulpiride to block strongly opiate withdrawal when compared to SCH 23390, as well as the effect of bromocriptine to increase opiate withdrawal suggest that D2 dopamine receptors may be primarily involved in the control of opiate withdrawal.

British Journal of Pharmacology (1997) 120, 1001–1006; doi:10.1038/sj.bjp.0700995
Evidence for direct and indirect mechanisms in the potent modulatory action of interleukin‐2 on the release of acetylcholine in rat hippocampal slices
Authors: Seto David , Kar Satyabrata , Quirion Rémi 
Published: August 2006

The biphasic nature of the potent modulatory action of interleukin‐2 (IL‐2) on hippocampal acetylcholine (ACh) release was investigated by use of brain slice superfusion.
Both the potentiating (10−13 m) and inhibitory (10−9 m) effects of IL‐2 on hippocampal ACh release were stimulation‐dependent and were blocked by a neutralizing IL‐2 receptor antibody, suggesting the activation of typical IL‐2 receptors in both cases.
Tetrodotoxin (TTX; 10 μm) failed to block the potentiation of ACh release induced by a very low concentration of IL‐2 (10−13m) suggesting a direct effect on cholinergic nerve terminals.
In contrast, the inhibitory effect seen at a higher concentration (10−9 m) was TTX‐sensitive, and hence indicative of an indirect action.
To establish the nature of this intermediate mediator, blockers of nitric oxide synthesis, and of opioid and γ‐aminobutyric acid (GABA) receptors were used. Only GABAA and GABAB receptor antagonists altered the inhibitory action of IL‐2, suggesting the participation of GABA as mediator.
Taken together, these results provide further evidence for the potent role of IL‐2 in the modulation of cholinergic function in the rat hippocampus.

British Journal of Pharmacology (1997) 120, 1151–1157; doi:10.1038/sj.bjp.0701002
The relative potencies of dendrotoxins as blockers of the cloned voltage‐gated K+ channel, mKv1.1 (MK‐1), when stably expressed in Chinese hamster ovary cells
Authors: Owen David G , Hall Adam , Stephens Gary , Stow John , Robertson Brian 
Published: August 2006

The mKv1.1 voltage‐gated K+ channel has been expressed stably in Chinese hamster ovary cells and whole‐cell currents recorded by the patch‐clamp method.
A range of structurally related peptide toxins (dendrotoxins) from the venom of green mamba (Dendroaspis angusticeps) and black mamba (Dendroaspis polylepis polylepis) snakes were tested for mKv1.1 channel blocking activity. Their potencies were compared based on EC50s derived from their respective concentration‐inhibition relationships.
The rank order of potency, thus determined was: Toxin K>γ‐dendrotoxin(γ‐Dtx)>δ‐Dtx>Toxin I=α‐Dtx>β‐Dtx.
Block was independent of voltage and no effects of the toxins on the kinetics of activation were observed. These results are consistent with a mechanism involving the block of closed channels.
A wide range of activity was observed even between toxins with an extremely high degree of sequence homology. Toxin K, in particular was an exquisitely potent blocker of the mKv1.1 channel, having an EC50 of 30 pm compared with 1.8 nm for δ‐Dtx in spite of 95% sequence identity.

British Journal of Pharmacology (1997) 120, 1029–1034; doi:10.1038/sj.bjp.0701004
Effects of l‐NG‐nitro‐arginine on noradrenaline induced contraction in the rat anococcygeus muscle
Authors: Hoyo Yolanda , Giraldo Jesús , Vila Elisabet 
Published: August 2006

The influence of l‐NG‐nitro‐arginine (l‐NOARG, 30 μm) on contractile responses to exogenous noradrenaline was studied in the rat anococcygeus muscle.
Noradrenaline (0.1–100 μm) contracted the muscle in a concentration‐dependent manner. l‐NOARG (30 μm) had no effect on noradrenaline responses.
Phenoxybenzamine (Pbz 0.1 μm) depressed by 46% (P<0.001) the maximum response and shifted to the right (P<0.001) the E/[A] curve to noradrenaline (pEC50 control: 6.92±0.09; pEC50 Pbz: 5.30±0.10; n=20).
The nested hyperbolic null method of analysing noradrenaline responses after phenoxybenzamine showed that only 0.61% of the receptors need to be occupied to elicit 50% of the maximum response, indicating a very high functional receptor reserve.
Contractile responses to noradrenaline after partial α1‐adrenoceptor alkylation with phenoxybenzamine (0.1 μm) were clearly enhanced by l‐NOARG.
The potentiating effect of l‐NOARG on noradrenaline responses after phenoxybenzamine was reversed by (100 μm) l‐arginine but not by (100 μm) d‐arginine.
These results indicate that spontaneous release of NO by nitrergic nerves can influence the α1‐adrenoceptor‐mediated response to exogenous noradrenaline.

British Journal of Pharmacology (1997) 120, 1035–1038; doi:10.1038/sj.bjp.0701005
Inhibition of synaptic transmission and epileptiform activity in central neurones by fluspirilene
Authors: Wang Su‐Jane , Lu Kwok‐Tung , Gean Po‐Wu 
Published: August 2006

Recent studies have shown that fluspirilene, a dopamine D2 receptor antagonist which is a long‐acting neuroleptic useful in the maintenance therapy of schizophrenic patients, also displays Ca2+ channel blocking activity. In the present study, we have investigated the effect of fluspirilene on synaptic transmission and epileptiform activity induced in slices of hippocampus and amygdala.
Fluspirilene reversibly suppressed the field excitatory postsynaptic potential (f‐e.p.s.p) in a concentration‐dependent manner in the area CAl of the hippocampus without affecting the size and shape of fibre volley. Fluspirilene also inhibited the intracellularly recorded e.p.s.p. in amygdala neurones without affecting the resting membrane potential or neuronal input resistance.
Fluspirilene increased the ratio of paired‐pulse facilitation suggesting a presynaptic mode of action.
Epileptiform activity induced in the disinhibited slices was suppessed by fluspirilene in a concentration‐dependent manner. This antiepileptic effect was occluded in slices pretreated with the adenosine A1 receptor agonist, N6‐cyclopentyladenosine (CPA).
It is concluded that fluspirilene‐induced synaptic inhibition is probably due to a reduction in presynaptic Ca2+ currents. In clinical trials, the low incidence of seizures provoked by fluspirilene might be related to its intrinsic ability to inhibit synaptic transmission and epileptiform activity.

British Journal of Pharmacology (1997) 120, 1114–1118; doi:10.1038/sj.bjp.0701008