bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of ethanol on eicosanoid synthesis by human gastric and colonic mucosal pieces
Authors: Goel R.K. , Tavares I.A. , Bennett A. 
Published: July 2012

Human gastric and colonic mucosa obtained at operation was cut into small pieces and incubated with different concentrations of ethanol.
Ethanol (5–40%) caused a concentration‐dependent increase in the amounts of prostaglandin E (PGE), thromboxane B2 (TXB2), 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α) and (up to 20% ethanol) leukotriene C4/D4 (LTC4/D4) in incubates of mucosal pieces from either region.
Higher concentrations of ethanol usually caused small increases or reductions of eicosanoid levels; gastric mucosal PGE and 6‐keto‐PGF1α were still increased by 100% ethanol, whereas TXB2 was unaltered, and LTC4/D4 was reduced. With the colonic mucosa, 100% ethanol increased PGE but reduced the other eicosanoids.
Gastric mucosal pieces incubated in water or phosphate buffer yielded generally similar amounts of eicosanoids. However, colonic mucosa yielded more when incubated in water, possibly indicating a greater sensitivity to osmotic damage. This difference between the two regions is consistent with the ability of the gastric mucosa to resist damage by water on its epithelial surface.
Segregation of discrete Gsα‐mediated responses that accompany homologous or heterologous desensitization in two related somatic hybrids
Authors: Kelly Eamonn , Keen Mary , Nobbs Peter , MacDermot John 
Published: July 2012

Prostacyclin and adenosine A2 receptors activate adenylate cyclase in the neuroblastoma hybrid cell lines NG108–15 and NCB‐20. Prolonged exposure of NG108–15 cells to iloprost (a stable analogue of prostacyclin) results in a subsequent reduction in the capacity for adenylate cyclase activation by iloprost, the adenosine analogue 5′‐(N‐ethyl)‐carboxamidoadenosine (NECA) or NaF. In contrast prolonged exposure of NCB‐20 cells to iloprost results only in the loss of iloprost responsiveness.
Iloprost pretreatment of NG108–15 cells also magnified the morphine‐dependent inhibition of iloprost‐stimulated adenylate cyclase activity from 36 to 48%. This change was not due to lower iloprost stimulation following desensitization, since the % inhibition of adenylate cyclase activity by morphine in control cells was constant irrespective of enzyme activity.
These heterologous effects observed in NG108–15 cells following iloprost pretreatment may involve changes in the Gsα protein, since there was a reduction of about 30% in the cholera toxin‐induced [32P]‐ADP‐ribosylation of a 45 kDa protein from cell membranes (corresponding to the extent of loss of NECA or NaF responsiveness). A similar reduction was not observed in NCB‐20 cells.
These results indicate that iloprost pretreatment induces different forms of desensitization in NG108–15 and NCB‐20 cell lines. The heterologous desensitization in the former may, like the human platelet, involve a functional loss of Gsα from the cell membrane. Changes in the activity of Gsα may also account for the heterologous effects on receptors that mediate inhibition of adenylate cyclase.
Anti‐inflammatory activity of bee venom peptide 401 (mast cell degranulating peptide) and compound 48/80 results from mast cell degranulation in vivo
Authors: Banks Barbara E.C. , Dempsey Christopher E. , Vernon Charles A. , Warner Jane A. , Yamey Jill 
Published: July 2012

The relationship between the anti‐inflammatory activity of the bee venom peptide 401 in the carrageenin‐induced oedema of the rat hind paw and its mast cell degranulating activity has been reinvestigated.
Mast cell degranulation caused by compound 48/80 (10 mg kg−1) or by allergen challenge in rats sensitized to Nippostrongylus brasiliensis also suppressed rat hind paw oedema in the same test.
The anti‐inflammatory activities of peptide 401 and compound 48/80 were partially suppressed by pretreatment of rats with mepyramine and methysergide, at doses (2.5 mg kg−1) that completely suppressed skin reactions to these mast cell‐derived amines. Pretreatment of rats with compound 48/80 also suppressed the apparent anti‐inflammatory actions of peptide 401 and of compound 48/80.
Injection of peptide 401 together with carrageenin increased the inflammatory response in the rat hind paw.
The anti‐inflammatory activity of peptide 401 and of compound 48/80 in the carrageenin‐induced swelling of the rat hind paw arises from mast cell degranulation in vivo.
Modulation of the reactivity of the guinea‐pig isolated trachealis by respiratory epithelium: Effects of cooling
Authors: Lamport Sheila J. , Fedan Jeffrey S. 
Published: July 2012

Examination has been made of the effects of epithelium removal on the reactivity of guinea‐pig trachealis to methacholine at 37°C and 22°C, and on responses to activation of the Na+/K+‐pump by abrupt temperature increase from 22°C to 37°C.
At 37°C, epithelium removal increased the sensitivity of isolated tracheal strips to methacholine without affecting the maximum isometric contractile response. Epithelium removal resulted at 22°C in a decrease in sensitivity to methacholine, i.e. an effect opposite to that seen at 37°C. While the maximum response of intact strips to methacholine was enhanced at 22°C, the maximum response of denuded preparations was decreased.
The increase in sensitivity to methacholine at 37°C after epithelium removal was mimicked in intact preparations by indomethacin (1 μm). Indomethacin did not mimic the decrease in methacholine sensitivity and maximum response caused by epithelium removal at 22°C.
Following incubation at 22°C, abrupt increase in temperature to 37°C elicited relaxation in both epithelium‐containing and epithelium‐denuded tracheal strips. In epithelium‐containing preparations the relaxation was more pronounced and followed by contraction. Ouabain (1 μm) converted the relaxation of denuded preparations to contraction, but was ineffective in intact strips. The relaxation of intact strips was, however, inhibited by a greater ouabain concentration (10 μm).
These findings indicate that the modulatory effect of the epithelium is temperature‐dependent. In cooled preparations, the epithelium enhances reactivity. At 37°C, an epithelium‐derived factor reduces reactivity, and this may partially be due to activation of the electrogenic Na+/K+‐pump.
Phaclofen‐insensitive presynaptic inhibitory action of (±)‐baclofen in neonatal rat motoneurones in vitro
Authors: Wang M.Y. , Dun N.J. 
Published: July 2012

Intracellular recordings were made from antidromically identified motoneurones in transverse spinal cord slices from neonatal (12–16 day) rats.
Superfusion of (±)‐baclofen (0.5–50 μm) reduced the excitatory postsynaptic potentials (e.p.s.ps) and inhibitory postsynaptic potentials (i.p.s.ps) evoked by dorsal root or dorsal root entry zone stimulation in a concentration‐dependent manner; the calculated EC50 was 2.4 μm. Baclofen in comparable concentrations also reversibly eliminated spontaneously occurring e.p.s.ps and i.p.s.ps.
(−)‐Baclofen was more effective as compared to baclofen in reducing the synaptic responses, whereas (+)‐baclofen at concentrations as high as 50 μm was ineffective.
Baclofen (< 5 μm) attenuated the synaptic responses without causing a significant change of passive membrane properties and depolarizations induced by exogenously applied glutamate. In addition to synaptic depression, baclofen (> 5 μm) caused a hyperpolarization associated with decreased membrane resistance in some of the motoneurones; the glutamate responses were also attenuated.
Baclofen reversibly depressed the spike after‐hyperpolarization of the motoneurones.
GABA (1–10 mm) depressed synaptic transmission and depolarized or hyperpolarized motoneurones. While potentiated by the uptake inhibitor nipecotic acid, the synaptic depressant effect of GABA was not antagonized by bicuculline.
The synaptic depressant effect of baclofen was neither blocked by GABAA antagonists bicuculline and picrotoxin (10–50 μm) nor by the GABAB antagonist phaclofen (0.1–1 mm).
It is suggested that baclofen depresses excitatory and inhibitory transmission in rat motoneurones by primarily a presynaptic mechanism in reducing the liberation of chemical transmitters from nerve endings via a phaclofen‐insensitive GABAB receptor.
The effects of epithelium removal on the actions of cholinomimetic drugs in opened segments and perfused tubular preparations of guinea‐pig trachea
Authors: Small R.C. , Good D.M. , Dixon J.S. , Kennedy I. 
Published: July 2012

Isolated segments of guinea‐pig trachea or perfused tracheal tubes were arranged for the recording of trachealis tension changes in Krebs solution containing indomethacin (2.8 μm).
In opened tracheal segments, epithelium removal caused modest (2–3 fold) potentiation of the effects of acetylcholine (ACh) and methacholine (MeCh) but failed to potentiate carbachol (CCh), bethanechol (BeCh), oxotremorine or KCl.
Pretreatment with ecothiopate potentiated effects of ACh and MeCh but not of CCh or BeCh. Removal of epithelium in ecothiopate‐treated tissue potentiated effects of ACh and MeCh but not of CCh or BeCh.
Guinea‐pig ileum challenged with ACh was used as a bioassay system for cholinesterase activity. Scrapings of tracheal epithelium did not hydrolyse ACh.
Histochemical staining revealed no fibres positive for acetylcholinesterase or pseudocholinesterase in the tracheal epithelium. However, the underlying tissues contained acetylcholinesterase‐positive nerve fibres and the trachealis muscle itself stained positively for pseudocholinesterase activity.
Neither tetrodotoxin (3 μm) nor hexamethonium (500 μm) modified the ability of epithelium removal to potentiate ACh.
In perfused tracheal tubes where spasmogens were added to the luminal perfusate, epithelium removal potentiated effects of ACh (31 fold), CCh (10 fold), oxotremorine (2 fold) and KCl.
In perfused tracheal tubes where spasmogens were added to the Krebs solution superfusing the adventitial surface of the tissue, epithelium removal significantly reduced the potency of CCh, oxotremorine and KCl.
It is concluded that the selectivity and magnitude of the potentiation of cholinomimetics caused by epithelium removal depends on the route by which the cholinomimetic agent gains access to the trachealis muscle. The potentiation of acetic acid esters of choline seen in opened tracheal segments does not reflect the loss of epithelial cholinesterase activity and does not depend on the activity of nervous reflex arcs in the tracheal wall. The reduced potency of adventitially‐applied cholinomimetics and KCl seen in epithelium‐denuded tissue strongly suggests that the epithelium can moderate trachealis sensitivity to cholinomimetic agents not only by releasing epithelium‐derived relaxing factor but also by acting as a barrier to drug diffusion.
Effects of metabolic inhibitors on endothelium‐dependent and endothelium‐independent vasodilatation of rat and rabbit aorta
Authors: Weir Cameron J. , Gibson Ian F. , Martin William 
Published: July 2012

Basal release of endothelium‐derived relaxing factor (EDRF) rendered endothelium‐containing rings of rat aorta 4.7 fold less sensitive to the contractile actions of phenylephrine and depressed the maximum response when compared with endothelium‐denuded rings. The responsiveness and maximum response to phenylephrine was, however, similar in rings of rabbit aorta with or without endothelium.
Rotenone (1 nm‐0.1 μm), an inhibitor of oxidative phosphorylation, induced a profound, irreversible blockade of phenylephrine‐induced tone in endothelium‐containing and endothelium‐denuded rings of rat aorta, but induced only slight inhibition of tone in rings of rabbit aorta.
2‐Deoxy glucose (10 mm), an inhibitor of glycolysis, had no effect on phenylephrine‐induced contraction in endothelium‐denuded rings of rat aorta, but inhibited reversibly the endothelium‐dependent depression of contraction in endothelium containing rings. 2‐Deoxy glucose had no effect on phenylephrine‐induced contraction in rings of rabbit aorta with or without endothelium.
Rotenone (0.1 μm) inhibited acetylcholine‐induced, endothelium‐dependent relaxation of phenylephrine‐contracted rings or rat and rabbit aorta. In endothelium‐denuded rings of rat aorta, relaxation induced by glyceryl trinitrate of isoprenaline was also inhibited, but relaxation induced by 8‐bromo cyclic GMP or dibutyryl cyclic AMP was not. Relaxation induced by verapamil on KCl‐contracted, endothelium‐denuded rings of rat aorta was also unaffected.
2‐Deoxy glucose (10 mm) inhibited acetylcholine‐induced, endothelium‐dependent relaxation of phenylephrine‐contracted rings of rat and rabbit aorta. In endothelium‐denuded rings of rat aorta, relaxation induced by glyceryl trinitrate and by isoprenaline was also inhibited, but relaxation induced by 8‐bromo cyclic GMP or dibutyryl cyclic AMP was not. Relaxation induced by verapamil on KCl‐contracted, endothelium‐denuded rings of rat aorta was also unaffected.
These data suggest that in rabbit and in rat aorta, rotenone inhibits acetylcholine‐induced relaxation by inhibiting EDRF production, and by depressing smooth muscle sensitivity to EDRF, respectively. They further suggest that 2‐deoxy glucose inhibits acetylcholine‐induced relaxation in both tissues by depressing the sensitivity to EDRF, probably as a result of reduced synthesis of cyclic GMP. The additional possibility that 2‐deoxy glucose inhibits EDRF production warrants further investigation.
The blockade by 2‐deoxy glucose of the endothelium‐dependent depression of phenylephrine‐induced tone in rat aorta probably reflects blockade of the actions of spontaneously released EDRF.
Contractile 5‐HT1 receptors in human isolated pial arterioles: correlation with 5‐HT1D binding sites
Authors: Hamel Edith , Bouchard Denis 
Published: July 2012

The 5‐hydroxytryptamine (5‐HT) receptor responsible for inducing vasoconstriction in human isolated pial arterioles has been pharmacologically characterized.
Of several 5‐HT agonists tested, 5‐carboxamidotryptamine (5‐CT) was the most potent and the rank order of agonist potency can be summarized as: 5‐CT > 5‐HT > RU 24969 = α‐methyl‐5‐HT = methysergide ≫ MDL 72832 = 2‐methyl‐5‐HT ≫ 2‐dipropylamino‐8‐hydroxy‐1,2,3,4‐tetrahydro‐naphthalene (8‐OH‐DPAT). With few exceptions, the maximal contractile responses of these agonists were comparable to that induced by 5‐HT.
A correlation analysis performed between the agonists vascular potency (pD2 values) and their affinities (pKD values) published at various subtypes of 5‐HT binding sites showed a positive significant correlation with rat cortical 5‐HT1B (r = 0.86; P < 0.01) and human caudate 5‐HT1D (r = 0.98; P < 0.005) subtypes.
Selective antagonists at 5‐HT2 (ketanserin, mianserin, MDL 11939) and 5‐HT3 (MDL 72222) sites were totally devoid of inhibitory activity on the 5‐HT‐induced contraction, an observation which agreed with the agonist data and further excluded activation of these receptors. In contrast, the 5‐HT1‐like/5‐HT2 antagonist methiothepin and the non‐selective 5‐HT1D compound metergoline inhibited with high affinity the contraction induced by 5‐HT with respective pA2 values of 8.55 ± 0.16 and 6.88 ± 0.05. This contractile response was, however, insensitive to 5‐HT1B (propranolol) and 5‐HT1C (mesulergine, mianserin) antagonists.
It is concluded that a 5‐HT1‐like receptor, which shares strong similarities with the 5‐HT1D binding sites identified in human caudate membranes, is mediating the vasocontractile action of 5‐HT in human pial arterioles.
Properties of 5‐hydroxytryptamine3 receptor‐gated currents in adult rat dorsal root ganglion neurones
Authors: Robertson Brian , Bevan Stuart 
Published: July 2012

Responses to 5‐hydroxytryptamine (5‐HT) were examined on rat dorsal root ganglion (DRG) neurones maintained in tissue cultures, by use of whole cell recording techniques.
5‐HT (usually 10 μm) evoked a depolarization associated with an increase in membrane conductance in 40% of DRG neurones. There was a considerable variation in the size and persistence of this response between different batches of cells.
The 5‐HT response was mimicked by applying the agonists 2‐methyl‐5‐HT (10 μm) and phenylbiguanide (10 μm). Responses were blocked by ICS 205–930 (100 nm), but not by methysergide (0.1–1.0 μm).
5‐HT currents could be carried by sodium and caesium ions, but not by choline ions. The amplitude and duration of the 5‐HT responses were dependent on the concentration of divalent cations in the extracellular solution: both became greater when calcium and magnesium concentrations were decreased.
Staurosporine, a putative antagonist of protein kinases, inhibited responses to 5‐HT.
Amantadine and sparteine inhibit ATP‐regulated K‐currents in the insulin‐secreting β‐cell line, HIT‐T15
Authors: Ashcroft Frances M. , Kerr Amanda J. , Gibson John S. , Williams Beatrice A. 
Published: July 2012

The effects of pharmacological agents that potentiate insulin release were studied on ATP‐regulated K‐currents (K‐ATP currents) in the insulin‐secreting β‐cell line HIT‐T15 by use of patch‐clamp methods.
The tricyclic drug, 1‐adamantanamine (amantadine), reversibly inhibited both whole‐cell currents (with a Ki of 120 μm) and single channel currents in inside‐out patches. This effect was principally due to an increase in a long closed state which reduced the channel open probability. The related compound, 1‐adamantanol, in which the amino group is substituted by a hydroxyl one, did not inhibit K‐ATP currents substantially.
The alkaloid, sparteine, reversibly inhibited both whole‐cell K‐ATP currents (Ki = 171 μm) and single channel currents in inside‐out patches.
The results suggest that sparteine and amantadine can block the K‐ATP channel from either side of the membrane and support the idea that at least part of the stimulatory effect of these agents on insulin secretion results from inhibition of this channel.
Differential effects of l‐arginine on the inhibition by NG‐nitro‐l‐arginine methyl ester of basal and agonist‐stimulated EDRF activity
Authors: Randall Michael D. , Griffith Tudor M. 
Published: July 2012

An isolated, buffer‐perfused rabbit ear preparation was used to investigate the influence of NG‐nitro‐l‐arginine methyl ester (l‐NAME) on endothelium‐dependent vasodilatation and modulation of vasoconstrictor responses and vascular conductance.
Acetylcholine (0.55 pmol‐1.6 nmol) caused dose‐related vasodilatation of preparations constricted by the combination of 5‐hydroxytryptamine and histamine (both 1 μm), with an ED50 = 31.1 ± 7.8 pmol and a maximum dilatation of 69.9 ± 4.3%. In the presence of 10 μm l‐NAME the dose‐response for vasodilator effects was shifted significantly (P < 0.001) to the right (ED50 = 3.07 ± 1.18 nmol) and there was a significant (P < 0.01) depression of the maximum response (Rmax = 44.3 ± 4.0%). The higher concentration of 100 μm l‐NAME completely abolished vasodilatation to acetylcholine. l‐Arginine (10 mm) did not reverse the inhibitory actions of l‐NAME at either concentration.
l‐NAME 100 μm, augmented vascular tone induced by 1 μm 5‐hydroxytryptamine and 1 μm histamine, thus altering the characteristics of both pressure/flow and conductance/flow relationships such that conductance was reduced at all flow rates. The augmentation of constrictor tone was reversed in a concentration‐dependent manner by l‐arginine (10 μm–10 mm) and the effect of l‐NAME on the conductance/flow relationships was similarly reversed by 10 mm l‐arginine. The augmentation of tone was endothelium‐dependent as it did not occur following functional destruction of the endothelium by perfusion of the vascular bed with the detergent CHAPS (0.3%) for 150 s.
In conclusion, l‐NAME is a potent inhibitor of agonist‐induced endothelium‐dependent vasodilatation. l‐NAME reduces vascular conductance in pharmacologically constricted preparations and this emphasizes the important role of EDRF in vascular regulation. The ability of l‐arginine to reverse l‐NAME‐induced inhibition of basal EDRF activity but not l‐NAME‐induced inhibition of agonist‐induced endothelium‐dependent relaxations suggests that there is pharmacological heterogeneity in the mechanisms responsible for the conversion of l‐arginine to EDRF.
The cardioprotective effect of γ‐glutamylcysteine ethyl ester during coronary reperfusion in canine hearts
Authors: Nishinaka Yasuto , Kitahara Shigehisa , Sugiyama Satoru , Yokota Mitsuhiro , Saito Hidehiko , Ozawa Takayuki 
Published: July 2012

The cardioprotective effect of γ‐glutamylcysteine ethyl ester was investigated on ischaemia‐reperfusion‐induced myocardial damage in anaesthetized dogs.
Open chest anaesthetized dogs were divided into four groups: 2 h occlusion of the left anterior descending coronary artery (LAD); 2 h LAD occlusion followed by 1 h reperfusion; 2 h LAD occlusion followed by 1 h reperfusion with administration of γ‐glutamylcysteine ethyl ester (10 mg kg−1 just before reperfusion); 2 h LAD occlusion followed by 1 h reperfusion with administration of GSH (the reduced form of glutathione, 10 mg kg−1 just before reperfusion).
After occlusion or reperfusion, heart mitochondria were prepared from the normal area and the occluded or the reperfused area, and mitochondrial function (rate of oxygen consumption in State III, and respiratory control index) was measured polarographically.
Mitochondrial GSH and GSSG (the oxidized form of glutathione) concentrations, and activities of glutathione peroxidase and glutathione reductase were measured.
Two h of LAD occlusion induced mitochondrial dysfunction with depletion of mitochondrial GSH concentration. One h of reperfusion after 2 h LAD occlusion induced significant mitochondrial dysfunction associated with a marked depletion of mitochondrial GSH concentration.
γ‐Glutamylcysteine ethyl ester reduced mitochondrial dysfunction and depletion of mitochondrial GSH concentration after 2 h LAD occlusion and 1 h reperfusion. In contrast, GSH did not prevent depletion of mitochondrial GSH concentration and mitochondrial dysfunction after 2 h LAD occlusion followed by 1 h reperfusion.
The activities of glutathione peroxidase and glutathione reductase did not change significantly in each group.
One h of reperfusion after 2 h occlusion of LAD induced ventricular arrhythmias. γ‐Glutamylcysteine ethyl ester markedly reduced the development of reperfusion arrhythmias, whilst GSH showed no protective effect.
γ‐Glutamylcysteine ethyl ester maintained mitochondrial GSH concentration, prevented reperfusion myocardial damage, and reduced reperfusion arrhythmias.