bluuebunny/crossref_metadata_2025_split huggingface dataset:
The booster injection of antigen during active sensitization of guinea‐pig modifies the anti‐anaphylactic activity of the PAF antagonist WEB 2086
Authors: Desquand S. , Lefort J. , Dumarey C. , Vargaftig B.B. 
Published: July 2012

Serum IgG levels of sensitized guinea‐pigs bled at various times after the booster injection were evaluated and its capacity to sensitize passively lung strips from normal guinea‐pigs assessed. Following the booster injection, both serum IgG and the ability to sensitize passively lung strips increased during the first week and decreased slowly thereafter.
The PAF antagonist WEB 2086 (3 mg kg−1, i.v.) blocked the anaphylactic bronchoconstriction induced by intravenous administration of ovalbumin (1 mg kg−1) when guinea‐pigs were challenged 2 and 4 days after the booster injection, but became ineffective when tested in guinea‐pigs challenged 7, 28 and 56 days after the booster injection.
The ability of WEB 2086 to reduce anaphylactic bronchoconstriction of guinea‐pigs challenged 2 and 4 days after the booster injection was unrelated to either the selective involvement of one type of immunoglobulin, low IgG titres in sera or a reduced sensitizing capacity.
The booster injection, which accounts for the loss of efficacy of WEB 2086 from the fourth day thereafter, probably operates as a PAF‐independent inflammatory challenge.
The protocol for immunisation and the day of experiment after the booster injection determines the sensitivity of the anaphylactic bronchoconstriction to inhibition by PAF antagonists.
NaF and guanine nucleotides modulate adenylate cyclase activity in NG108‐15 cells by interacting with both Gs and Gi
Authors: Kelly Eamonn , Keen Mary , Nobbs Peter , MacDermot John 
Published: July 2012

NaF (10 mm) produced a 2–3 fold increase in adenylate cyclase activity in homogenates of NG108‐15 cells incubated in the presence of 1 μm GTP. Higher concentrations of NaF suppressed adenylate cyclase activity.
In the presence of the adenosine receptor agonist 5′‐(N‐ethyl)‐carboxamidoadenosine (NECA; 100 μm) or the prostacyclin receptor agonist iloprost (10 nm), NaF produced a much smaller increase in adenylate cyclase activity, whereas in the presence of a saturating concentration of iloprost (1 μm), NaF only inhibited adenylate cyclase activity.
Similarly, Gpp(NH)p activated basal adenylate cyclase activity, and inhibited 1 μm iloprost‐activated enzyme activity. In the presence of 10 μm forskolin, NaF or Gpp(NH)p increased adenylate cyclase activity synergistically. Analysis of concentration‐effect curves indicated that NaF (2 mm) or Gpp(NH)p (100 μm) increased the potency with which forskolin activated adenylate cyclase, whilst reducing the maximum activation of adenylate cyclase by iloprost.
Opiate receptors mediate inhibition of adenylate cyclase, and the opiate agonist morphine (100 μm) reduced the capacity of NaF or Gpp(NH)p to inhibit iloprost‐activated adenylate cyclase. Unexpectedly, pertussis toxin treatment enhanced the ability of NaF or Gpp(NH)p to inhibit iloprost‐activated adenylate cyclase.
In the absence of GTP, NaF and Gpp(NH)p remained able both to activate basal adenylate cyclase and to be synergistic with forskolin in activating the enzyme. In contrast the ability of NaF and Gpp(NH)p to inhibit iloprost‐activated adenylate cyclase was substantially lost in the absence of added GTP.
These results suggest that NaF modulates adenylate cyclase activity in NG108‐15 cell membranes by interacting with the α subunits of both Gs and Gi regulatory proteins. The effects of NaF and Gpp(NH)p are critically dependent on the prior mode and extent of activation or inhibition of this transmembrane signalling pathway. This simple system may be of use in assessing alterations in Gs‐Gi interaction following manipulations such as hormone receptor desensitization.
Evaluation of the bronchodilator properties of Ro 31–6930, a novel potassium channel opener, in the guinea‐pig
Authors: Paciorek P.M. , Cowlrick I.S. , Perkins R.S. , Taylor J.C. , Wilkinson G.F. , Waterfall J. F. 
Published: July 2012

Ro 31–6930 (0.001‐0.3 μm), cromakalim (0.03‐3.0 μm), salbutamol (0.001‐0.3 μm) and theophylline (0.3–100 μm) evoked dose‐related reductions in guinea‐pig spontaneous tracheal tone with IC50 values of 0.044, 0.20, 0.021 and 21.0 μm respectively. All four agents also relaxed tone supported by betahistine, carbachol, 5‐hydroxytryptamine (5‐HT), leukotriene D4 (LTD4), U46619 and prostaglandin D2 (PGD2). The order of potency of tracheal relaxants was always salbutamol > Ro 31–6930 > cromakalim > theophylline.
All four agents evoked dose‐related reductions in 5‐HT‐ and histamine‐induced bronchoconstriction in pithed vagotomised guinea‐pigs. The dose of Ro 31–6930 producing 50% inhibition of a 5‐HT bronchoconstriction was 11.6 μg kg−1 and the dose producing 50% inhibition of a histamine bronchoconstriction was 4.4 μg kg−1. Salbutamol was approximately 4–5 times more potent than Ro 31–6930 whilst cromakalim was approximately 10 times less potent than Ro 31–6930 as a bronchodilator. Theophylline was markedly less potent than any of the other agents.
Ro 31–6930, cromakalim, salbutamol and theophylline each protected conscious guinea‐pigs from histamine‐induced respiratory distress. Ro 31–6930 and salbutamol were each effective at oral doses of 1.0 and 3.0 mg kg−1 whilst cromakalim was effective at oral doses of 3.0 and 10.0 mg kg−1. Theophylline showed activity only at 300 mg kg−1 p.o.
Ro 31–6930 is a novel potassium channel opener which is a potent relaxant of guinea‐pig tracheal smooth muscle in vitro and a bronchodilator in vivo.
Development of tolerance to the effects of vigabatrin (γ‐vinyl‐GABA) on GABA release from rat cerebral cortex, spinal cord and retina
Authors: Neal M.J. , Shah M.A. 
Published: July 2012

The effects of acute and chronic vigabatrin (γ‐vinyl‐GABA) (GVG) administration on γ‐aminobutyric acid (GABA) levels and release in rat cortical slices, spinal cord slices and retinas were studied.
GVG (250 mg kg−1 i.p.) administered to rats 18 h before death (acute administration) produced an almost 3 fold increase in GABA levels of the cortex and spinal cord and a 6 fold increase in retinal GABA. The levels of glutamate, aspartate, glycine and taurine were unaffected.
When GVG (250 mg kg−1 i.p.) was administered daily for 17 days (chronic administration) a similar (almost 3 fold) increase in cortical GABA occurred but the increases in spinal and retinal GABA were reduced by approximately 40%.
Acute administration of GVG strikingly increased the potassium‐evoked release (KCl 50 mm) of GABA from all three tissues. This enhanced evoked release was reduced by about 50% in tissues taken from rats that had been chronically treated with GVG.
Acute administration of GVG reduced GABA‐transaminase (GABA‐T) activity by approximately 80% in cortex and cord and by 98% in the retina. Following the chronic administration of GVG, there was a trend for GABA‐T activities to recover (significant only in cortex). Acute administration of GVG had no effect on glutamic acid decarboxylase (GAD) activity in cortex or spinal cord. However, chronic treatment resulted in significant decreases in GAD activity in both the cortex and cord (35% and 50% reduction respectively).
The K‐evoked release of glutamate, aspartate, glycine and taurine from cortical slices and the K‐evoked release of glycine from spinal slices and retinas were not affected by either acute or chronic GVG treatment.
These experiments indicate that GVG treatment increases specifically the K‐evoked release of GABA and that tolerance can develop to this enhancing effect of GVG on central GABA release. This tolerance may result from increased feedback inhibition of GAD with a consequent reduction of presynaptic GABA stores.
No effect of pertussis toxin on peripheral prejunctional α2‐adrenoceptor‐mediated responses and on endothelium‐dependent relaxations in the rat
Authors: Docherty J.R. 
Published: July 2012

We have investigated the effects of pertussis toxin treatment on a variety of peripheral tissues in the rat.
Incubation with pertussis toxin (1 μg ml−1) in vitro failed to alter the negative inotropic actions of acetylcholine in rat left atria.
Pretreatment with pertussis toxin (6 μg kg−1, i.v., 3–4 days) abolished the negative inotropic actions of acetylcholine in rat left atria.
Pretreatment with pertussis toxin (40 μg kg−l, i.v., 3–4 days) failed to alter the prejunctional inhibitory actions of the α2‐adrenoceptor agonist xylazine, either in terms of the isometric contraction to a single stimulus in rat vas deferens or in terms of stimulation‐evoked overflow of tritium in atria pre‐incubated with [3H]‐noradrenaline.
Pretreatment with pertussis toxin (6 μg kg−1, i.v., 3–4 days) failed to affect, and pertussis toxin (40 μg kg−1, i.v., 3–4 days) potentiated endothelium‐dependent relaxations of rat aorta to histamine and acetylcholine.
It seems unlikely that peripheral prejunctional actions of α2‐adrenoceptor agonists or endothelium‐dependent relaxations of rat aorta involve pertussis toxin‐sensitive G proteins.
Glibenclamide is a competitive antagonist of the thromboxane A2 receptor in dog coronary artery in vitro
Authors: Cocks Thomas M. , King Susannah J. , Angus James A. 
Published: July 2012

Glibenclamide, a sulphonylurea oral hypoglycaemic agent is a widely used antagonist of cromakalim‐activated K+ channels in smooth muscle.
In isolated ring segments of the large circumflex coronary artery from the dog, glibenclamide (1–30 μm) caused a concentration‐dependent reduction in both spontaneous isometric force and contractions induced by U46619, a thromboxane A2‐mimetic.
Glibenclamide behaved as a competitive antagonist of U46619 with an estimated pKB (‐log KB) value of 6.2 by Schild regression analysis (slope 1.07).
Glibenclamide (30 μm) was apparently selective since it had no effect on the concentration‐contraction curves to endothelin‐1, noradrenaline or KCl.
We suggest that this additional property of glibenclamide should be considered in any smooth muscle study where active force is raised by either the exogenous application or endogenous generation of thromboxane A2.
Evaluation of the effect of azapropazone on neutrophil migration in regional myocardial ischaemia/reperfusion injury in rabbits
Authors: Mousa Shaker A. , Brown Reginald , Thoolen Martin J.M. , Smith Ronald D. 
Published: July 2012

The purpose of the present study was to determine the myocardial cytoprotective efficacy of azapropazone (AZA) and its potential site of action on neutrophil infiltration into reperfused/ischaemic myocardium with or without in vivo activation of neutrophils in rabbits.
AZA, 100 mg kg−1, was administered i.v. 10 min after occlusion of the left circumflex (LCX) artery in rabbits with and without pretreatment with phorbol myristate acetate ester (PMA). The LCX occlusion was then released at 10 min after AZA administration. Haemodynamic parameters (heart rate, LV pressure, mean arterial blood pressure and dp/dt) were monitored throughout the experiment. After 60 min reperfusion, the area at risk was delineated and the heart was then excised and divided into epi‐ and endocardial pieces for analysis of myeloperoxidase activity.
AZA inhibited neutrophil infiltration into the reperfused/ischaemic rabbit myocardium with and without PMA treatment. The inhibition of neutrophil infiltration was more apparent in the epicardium than in the endocardium. Additionally, AZA inhibited to a similar extent the in vivo PMA‐stimulated neutrophil migration into the epicardium and endocardium area at risk. AZA had no significant effect on the haemodynamic parameters as compared to control.
AZA administered in an anaesthetized rabbit model of LCX occlusion/reperfusion resulted in the reduction of infarct size.
It is concluded that AZA has significant inhibitory effects on neutrophil migration which might contribute to its myocardial cytoprotective effect.
CGP 35348, a new GABAB antagonist, prevents antinociception and muscle‐relaxant effect induced by baclofen
Authors: Malcangio M. , Ghelardini C. , Giotti A. , Malmberg‐Aiello P. , Bartolini A. 
Published: July 2012

CGP 35348, a new GABAB antagonist, was examined on antinociception induced by (±)‐baclofen by use of the hot plate and writhing tests in mice and the paw pressure test in rats. CGP 35348 was also studied in mice on (±)‐baclofen‐induced impairment of rota‐rod performance.
CGP 35348, injected either i.p. (60–100 mg kg−1 in mouse) or intracerebroventricularly (i.c.v.) (0.5–2.5 μg per mouse; 25 μg per rat) prevented (±)‐baclofen‐induced antinociception.
CGP 35348 did not modify oxotremorine‐ and morphine‐induced antinociception in mice and rats.
CGP 35348 (2.5 μg i.c.v. per mouse) also prevented (±)‐baclofen‐induced impairment of the rota‐rod test.
Two other GABAB antagonists, phaclofen (50 μg i.c.v. per mouse) and 2‐OH‐saclofen (2.5 μg‐10 μg i.c.v. per mouse) did not modify (±)‐baclofen‐induced antinociception.
These results suggest that, at present, CGP 35348 is the only compound able to antagonize (±)‐baclofen‐induced antinociception.
Effect of pertussis pretreatment on plasma glucose and insulin responses to lithium in rats
Authors: Hermida O. García , Fontela T. , Ghiglione M. , Uttenthal L.O. 
Published: July 2012

Administration of lithium to rats causes a rise in plasma glucose and suppresses glucose‐stimulated insulin secretion. These effects are blocked by the α2‐adrenoceptor antagonist, yohimbine.
Pretreatment of rats with Bordetella pertussis toxin resulted in a reversal of the usual plasma glucose and insulin responses to intravenously administered lithium (4 mEq kg−1). There was a slow fall in plasma glucose, while plasma insulin rose to 267 ± 42% (± s.e.mean) of control values at 30 min. The effect of lithium on glucose‐stimulated insulin secretion was also reversed; there was a marked increase in the insulin response which contrasted with the suppression seen in normal controls.
In perifused islets of Langerhans isolated from pertussis pretreated rats, the previously described inhibition by lithium of the second phase of glucose‐stimulated insulin secretion from normal islets was almost completely abolished.
The results are consistent with the hypothesis that these effects of lithium are mediated by the influence of catecholamines on the islets. When the inhibitory effect of α2‐adrenoceptors is abolished by pertussis treatment, which blocks the action of the inhibitory guanine nucleotide‐binding protein Gi, effects of β‐adrenoceptor stimulation predominate, leading to an increased secretion of insulin.
Human interleukin‐1 induces a rapid relaxation of the rabbit isolated mesenteric artery
Authors: Marceau François , Petitclerc Eric , DeBlois Denis , Pradelles Philippe , Poubelle Patrice E. 
Published: July 2012

Strips of rabbit superior mesenteric artery, precontracted with phenylephrine, relaxed when exposed to human recombinant interleukin‐1 (IL‐1) of the α or β types. The effect was observed within 10 min, was optimal 32 min after the application of the cytokines and concentration‐dependent (12–290 pm).
IL‐1α and IL‐1β were equipotent in relaxing the rabbit mesenteric artery. A synthetic fragment corresponding to IL‐1β 163–171 was approximately one million fold less active than IL‐1β. The tripeptide Lys‐d‐Pro‐Thr, an analogue of IL‐1β 193–195, was inactive as an antagonist of IL‐1β on the preparation.
Indomethacin (2.8 μm) prevented or acutely reversed IL‐1‐induced relaxations in the rabbit mesenteric artery. Purified haemoglobin (10 μm) or the removal of endothelium had no effect on relaxations elicited by IL‐1β.
The preparation exhibited some selectivity for IL‐1 as recombinant human tumour necrosis factor‐α (TNF‐α), IL‐2 or IL‐6 failed to influence it. TNF‐α was not synergistic with a subthreshold concentration of IL‐1β.
Immunoreactive 6‐keto‐prostaglandin F1α and prostaglandin E2 were increased in the bathing fluid of isolated mesenteric arteries exposed to IL‐1β as compared to controls.
A supernatant of lipopolysaccharide‐stimulated human monocytes produced a relaxation of the preparation with a profile similar to that produced with IL‐1s and there was a good quantitative agreement between the extent of the relaxation and the enzyme immunoassay measurements of IL‐1α and IL‐1β in the supernatant. Furthermore the relaxation of crude monocyte IL‐1 was prevented by preincubating with antibodies to IL‐1α and IL‐1β. This experiment illustrates the possible use of the preparation for bioassay of IL‐1.
It is concluded that either form of IL‐1 relaxes the precontracted rabbit mesenteric artery by a prostaglandin‐dependent, nitric oxide‐independent mechanism. The model is also useful for distinguishing the mechanism of IL‐1‐induced hypotension in vivo in rabbits.
Maintenance of functional activity of human pulmonary arteries after cryopreservation
Authors: Ellis P. , Müller‐Schweinitzer E. 
Published: July 2012

Human intrapulmonary arteries have been investigated in vitro in fresh tissue or after storage at −190°C in foetal calf serum containing 1.8 m dimethyl sulphoxide.
After cryopreservation of the arteries, maximal contractile force was reduced to 76%. This was assessed by the responses (in g) to 10 nm of the thromboxane analogue, U 46619.
Constricting agonists such as noradrenaline, 5‐hydroxytryptamine, histamine and U 46619 stimulated fresh and frozen/thawed arteries producing pD2 values similar to the respective values determined on fresh tissues.
Endothelium‐independent relaxant responses of U 46619‐precontracted arteries to prostacyclin (PGI2), aminophylline and papaverine were generally unchanged after storage. The same was true for relaxant response to the potassium channel activator P‐1075 whereas the pD2 values for SDZ PCO 400, RP 49356 and cromakalim were somewhat diminished.
Nevertheless, a significant correlation was obtained when the apparent pD2 values for all agonists on fresh and frozen/thawed tissues were compared (P < 0.001).
The evidence suggests that after cryopreservation of human intrapulmonary arteries at −190°C, mechanisms of both contraction and relaxation are well‐maintained.
Prejunctional modulatory action of neuropeptide Y on responses due to antidromic activation of peripheral terminals of capsaicin‐sensitive sensory nerves in the isolated guinea‐pig ileum
Authors: Takaki Miyako , Nakayama Sosogu 
Published: July 2012

The effect of neuropeptide Y (NPY) on motor responses produced by activation of capsaicin‐sensitive primary afferents in the guinea‐pig isolated ileum was determined by use of capsaicin itself and electrical mesenteric nerve stimulation as stimuli.
NPY inhibited or suppressed the cholinergic contractile response produced by electrical mesenteric nerve stimulation while leaving the contractile response to a threshold concentration of capsaicin.
NPY had no effect on motor responses produced by a submaximal concentration of substance P, the putative endogenous mediator of the ‘efferent’ function of sensory fibres in this preparation.
It is concluded that NPY exerted a prejunctional inhibitory action on transmitter release from peripheral endings of capsaicin‐sensitive nerves at interneuronal synapses.
Regional haemodynamic effects of prolonged infusions of human α‐calcitonin gene‐related peptide in conscious, Long Evans rats
Authors: Gardiner S.M. , Compton A.M. , Kemp P.A. , Bennett T. , Foulkes R. , Hughes B. 
Published: July 2012

Haemodynamic measurements were made in conscious, Long Evans rats chronically instrumented for the assessment of changes in regional blood flows (renal, mesenteric and hindquarters, or internal and common carotid) and systemic arterial blood pressure and heart rate, before, during and after 3 day infusions of vehicle or human α‐calcitonin gene‐related peptide (CGRP) (1.5 or 15 nmol kg−1 h−1).
In animals with renal, mesenteric and hindquarters flow probes (n = 8), during the first day of infusion of human α‐CGRP (1.5 nmol kg−1 h−1) there was sustained tachycardia and hypotension, a sustained reduction in renal flow, a transient reduction in mesenteric flow and a relatively well‐maintained increase in hindquarters flow. All these effects were significantly different from the changes seen in vehicle‐infused rats (n = 8), but calculation of vascular conductances showed only the late mesenteric vasodilatation and the sustained hindquarters vasodilatation were different from the changes in vehicle‐infused rats. However, by the second day of infusion and thereafter cardiovascular variables in the animals receiving vehicle and those receiving human α‐CGRP were not different.
Nine animals instrumented with probes to monitor changes in internal and common carotid haemodynamics initially received human α‐CGRP infused at a rate of 1.5 nmol kg−1 h−1. Three of these animals still showed some response to the human α‐CGRP (tachycardia, hypotension, hyperaemic vasodilatation) throughout the second day of infusion and hence were taken through the 3 day infusion protocol. When the infusion was stopped on the fourth day all these animals showed reversal of the effects of human α‐CGRP. The other 6 animals in the original group showed complete desensitization to the effects of human α‐CGRP by the end of the second day of infusion (as seen in the group instrumented with renal, mesenteric and hindquarter probes). Therefore, in order to assess the extent of desensitization, at the beginning of the third day the dose of human α‐CGRP was increased to 15 nmol kg−1 h−1. The resulting tachycardia, hypotension and hyperaemia in the carotid vascular beds were significant, (but no greater than the initial responses to human α‐CGRP at 1.5 nmol kg−1 h−1). These effects were maintained throughout the third infusion day, but there was some desensitization to the effects of this higher dose of human α‐CGRP by the beginning of the fourth infusion day. However, when the infusion was stopped there was clear reversal of the effects of human α‐CGRP.
The results indicate substantial inter‐individual variation in the haemodynamic effects of prolonged infusions of human α‐CGRP in conscious, Long Evans rats. However, since increasing the dose of human α‐CGRP overcame the desensitization, it is feasible that, in the clinical setting, maintained increases in internal carotid blood flow could be achieved by individually‐adjusted infusions of human α‐CGRP.
Effects of midaglizole, a new hypoglycaemic drug on the electrophysiological properties of guinea‐pig papillary muscle
Authors: Noguchi Noriyasu , Hasegawa Junichi , Mashiba Hiroto 
Published: July 2012

The electrophysiological effects of midaglizole, a new oral hypoglycaemic agent which is an α2‐adrenoceptor antagonist, were assessed in the reserpinized ventricular myocardium of the guinea‐pig.
Midaglizole suppressed the maximal rate of rise (V̇max) and the amplitude of action potentials (APA) of the fast and the slow responses in a concentration‐dependent manner without influencing the resting potentials.
Voltage‐dependency of the V̇max block of the action potentials by midaglizole (10 μm) did not appear in solutions containing various concentrations of KCl.
It is concluded that midaglizole has inhibitory effects on the fast Na+ and slow Ca2+ currents of the membrane independent of the blockade of myocardial α‐adrenoceptors, and that these effects may be significant in some clinical uses of the drug.