bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alphaxalone reveals GABAA receptor-mediated inhibition in guinea-pig ileum
Authors: Healing Claire , Hilton Trudi , Simmonds Michael 
Published: April 2011

Abstract
Contractions of the transmurally stimulated guinea-pig ileum were not affected by 10 μM bicuculline, a competitive GABAA receptor antagonist. The GABAA potentiator alphaxalone depressed the responses to 2 and 20 Hz stimulation by 20% and 40%, respectively, but had no effect on 0·2 Hz responses. The depressions were prevented by 10 μM bicuculline. This suggests that endogenous activation of GABAA receptors during transmural stimulation was normally subthreshold but, when pharmacologically potentiated, inhibitory effects were seen.
The effect of Ca deprivation and of Ca-blocking drugs on oxytocin-induced contractions of the male mouse anococcygeus
Authors: Gibson A , Shaw C R 
Published: April 2011

Abstract
Oxytocin (4 nM)-induced contractions of the male mouse anococcygeus were rapidly and completely lost in EGTA (2 mM)-containing, Ca-free Krebs solution. Contractions were also lost, although more slowly, in Ca-free Krebs solution without EGTA; under such conditions, readdition of Ca did not by itself cause contraction, but readdition of Ca (0·1–2·5 mm) in the presence of 4 nM oxytocin resulted in a rapid contractile response. These Ca-induced responses, in the presence of oxytocin, and those to oxytocin in normal Ca-containing Krebs solution, were unaffected by nitrendipine (0·01–1 μM). Contractions to oxytocin were completely blocked by the calmodulin antagonists trifluoperazine (50 μM) and W-7 (75 μM). It is concluded that oxytocin-induced contraction of the mouse anococcygeus does not require opening of nitrendipine-sensitive Ca channels, and there is no Ca-independent component of the contractile response; the cellular mechanisms linked to the oxytocin receptor in the anococcygeus are therefore different from those in the uterus.
Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat
Authors: Barwell C J , Basma A N , Lafi M A K , Leake L D 
Published: April 2011

Abstract
The selectivity of the naturally occurring mine, N,N-dimethyltyramine (hordenine) for monoamine oxidase (MAO) and its action upon isolated vasa deferentia of the rat was investigated. Hordenine was deaminated by rat liver MAO with a Michaelis constant of 479 μM and maximum velocity of 128 nmol (mg protein)−1 h−1 compared with 144 μM and 482 nmol (mg protein)−1 h−1 for tyramine. Studies, with selective irreversible inhibitors of MAO, showed that hordenine was a highly selective substrate for MAO-B of liver and that it was not deaminated by the MAO-A of intestinal epithelium. In contrast to tyramine, hordenine did not produce contractions of isolated vasa deferentia. However, 25 μM hordenine potentiated contractile responses of vasa, from control animals, to submaximal doses of noradrenaline and inhibited responses to tyramine. It did not alter responses, to noradrenaline, of vasa denervated by chronic pretreatment of rats with guanethidine. Therefore, it appears that hordenine acted as an inhibitor of noradrenaline uptake, in isolated vasa deferentia. These results indicate that dietary-hordenine is unlikely to be deaminated by intestinal MAO as this is predominantly MAO-A. Consequently, it is likely to be absorbed and could affect the sympathetic nervous system, by virtue of its action as an inhibitor of noradrenaline uptake.
The Effect of Captopril on the Membrane Properties of Central Neurons In-vitro
Authors: Robinson E L , Greenfield S A 
Published: April 2011

Abstract
Captopril, a potent antihypertensive that acts via inhibition of angiotensin converting enzyme also has apparent central actions. Its effects on membrane properties on particular central neurons in-vitro has therefore been investigated. In the substantia nigra, where there is a high concentration of angiotensin converting enzyme, captopril caused a dose-dependent depolarization without any apparent change in conductance, but possibly requiring the integrity of the dendritic arbour. A similar effect occurred when captopril was applied to neurons in either the thalamus or hippocampus, where levels of angiotensin converting enzyme are relatively low. Further studies with homologues of captopril revealed that the — SH group on the molecule was a prerequisite of the effect observed. It is concluded that the — SH group on the captopril molecule has an electrogenic effect on diverse central neurons, independent of inhibition of angiotensin converting enzyme, but preferentially manifest at the level of the dendrite.
The Effects of Enprostil and RS-86505-007 on In-vitro Intestinal Permeability of Rabbit and Monkey
Authors: Grass George M , Sweetana Stephanie A , Bozarth Carol A 
Published: April 2011

Abstract
Enprostil is a prostaglandin E2 analogue characterized as a racemic mixture of four stereoisomers. Enprostil and a single isomer, RS-86505-007, were evaluated for their effects on the permeability of actively and passively transported compounds in segments of small intestine from rabbits and monkeys. Consistent with human in-vivo studies, which have demonstrated decreases in absorption of D-xylose, both compounds inhibited D-glucose transport. The passively transported compounds mannitol and progesterone were also less permeable in this model in the presence of enprostil or RS-86505-007. In contrast to the concentration-dependent inhibition displayed by ouabain, RS-86505-007 had no effect on purifed Na+K+-ATPase. It is suggested that an effect of a general nature, possibly an increase in the barrier properties at the intestinal surface, may explain the transport inhibition. Of two other enprostil isomers, RS-86812-007 inhibited D-glucose transport in rabbit small intestine, while RS-86505-008 had no effect. The prostaglandin E1 analogue misoprostol was ineffective in monkey and poorly effective in rabbit. This suggests that the inhibition of D-glucose transport by enprostil and its active stereoisomers is mediated through some structurally specific receptor interaction.
Induction of hepatic microsomal drug metabolizing enzyme system by levamisole in male mice
Authors: Dalvi R R , Terse P S 
Published: April 2011

Abstract
To examine the effect of levamisole on the hepatic drug metabolizing enzyme system of mice, levamisole at a dose of 20 mg kg−1 day−1 was administered i.p. for 5 days. Compared with the control values, the levamisole treatment significantly increased the amount of cytochrome P450 and cytochrome b5 and the in-vitro activities of aminopyrine N-demethylase, benzphetamine N-demethylase and aniline hydroxylase. In contrast, there was no change in microsomal NADPH-cytochrome c reductase activity in-vitro or in the relative liver weight and microsomal protein content compared with the corresponding values for control mice. Furthermore, in-vivo induction of drug metabolism was demonstrated by decreased pentobarbitone sleeping times after levamisole pretreatment. These results indicate that certain hepatic microsomal mixed function oxidases of mice are induced by levamisole, the drug that is frequently used as an anthelmintic in veterinary medicine and as an immunostimulant drug in human medicine.
The preferential effects of chloroquine on the IgM and IgG subclass responses to TI and TD antigens in BALB/cAn mice
Authors: Lewis G M , Slack J H 
Published: April 2011

Abstract
This study has determined the effects of chloroquine on the IgM and the IgG subclass responses of BALB/cAn mice to both thymus-independent (TI) and thymus-dependent (TD) antigens, and has found that in antigen-unprimed BALB/cAn mice chloroquine adversely affects antibody responses to both TI and TD antigens. However, in antigen-primed mice the immune responses to TD antigens were unaffected by chloroquine. The IgG1 subclass response, but not necessarily other IgG subclass or IgM responses to TI and TD antigens, was adversely affected by chloroquine in unprimed mice only. Thus, in unprimed, but not in antigen-primed, BALB/cAn mice, chloroquine preferentially decreased the IgG1 subclass responses to both TI and TD antigens.
Differential effects of ketoprofen on the pharmacokinetics of sulphadimethoxine in fast and slow acetylator rabbits
Authors: Imamura Yorishige , Mori Hiroyuki , Otagiri Masaki 
Published: April 2011

Abstract
Intravenously co-administered ketoprofen decreased the plasma concentration of sulpha-dimethoxine (SDM) after intravenous bolus administration to fast acetylator rabbits, and significantly increased the total body clearance (CLtot) and steady-state volume of distribution (Vdss) of SDM. On the other hand, ketoprofen had little effect on the plasma concentration of SDM in slow acetylator rabbits. When SDM was intravenously administered in combination with ketoprofen, an increase in the plasma concentration of N4-acetylsulphadimethoxine, a major metabolite of SDM that strongly displaces SDM from its binding sites, was observed in all rabbits, but the increase was much larger in fast acetylators. We conclude that the acetylation capacity for SDM is a factor determining the pharmacokinetic interaction between SDM and ketoprofen in rabbits.
Inhibition of noradrenaline release from cerebrocortical synaptosomes and stimulation of synaptosomal Na+, K+-ATPase activity by morphine in rats
Authors: Nishikawa Takashige , Shimizu Shin-Ichiro 
Published: April 2011

Abstract
The effects of morphine on noradrenaline (NA) release from rat cerebrocortical synaptosomes and on the synaptosomal Na+, K+-ATPase activity were determined. Morphine (10−3-10−5 M) caused a dose-related inhibition of enhanced prelabelled [3H]NA release evoked by a high concentration of K+ from synaptosomes and this inhibitory action of morphine was antagonized by the specific antagonist naloxone (10−4, 10−5 M). Morphine dose-dependently stimulated the synaptosomal Na+, K+-ATPase activity but not Ca2+-ATPase activity in the incubation medium containing 2.2 × 10−6 4.7 × 10−7 M free Ca2+, and this stimulatory effect was antagonized by naloxone. These results suggest that morphine may have some role in the suppression of membrane depolarization and/or the release of NA through its stimulatory action on the Na+, K+-ATPase activity in rat cerebral cortex.
Model Systems for the Evaluation of Mucolytic Drugs: Acetylcysteine and S-Carboxymethylcysteine
Authors: Livingstone Carina R , Andrews Mary A , Jenkins Susan M , Marriott Christopher 
Published: April 2011

Abstract
The therapeutic place of mucolytic drugs remains uncertain; clinical studies have seldom demonstrated significant benefit and the activity of such agents is poorly understood. In this study the effects of the mucolytic agents acetylcysteine (AC) and S-carboxymethylcysteine (SCMC) have been assessed in-vitro, using purified mucus gels and tracheal explant systems and in-vivo, in the mini-pig tracheal pouch model, in order to elucidate their mechanisms of action. A reduction in the elastic modulus (up to 70% over the frequency range 0.2-20Hz) was apparent after treatment of mucus gels in-vitro with AC (p &lt; 0.05), but not with SCMC. Gel chromatography indicated that AC reduced the mucus glycoprotein to smaller subunits and a breakdown of gel structure was apparent when visualized using a cryofracture technique. SCMC treated gels were comparable with control samples. Mucus production was assessed in isolated rat trachea by monitoring the uptake and release of [3H] glucosamine. AC (5–15 mM) did not affect secretion whereas SCMC (5 and 10 mM) reduced the production of radiolabelled material (24 and 37%, respectively) over 24 h (P &lt; 0.05). Single oral doses of SCMC and AC (20 mg kg−1) were administered to mini-pigs and mucus collected from tracheal pouches; no significant changes in the rheological or biochemical properties of the secretion could be determined. The in-vitro mucolytic activity of AC depends upon a direct action on the secretion, SCMC appears able to reduce production of the mucus glycoprotein. Wide inter-and intra-individual variation in the properties of the secretion would suggest that such effects are not readily demonstrated in-vivo.
In-vitro Effect of Pirenzepine on Motility of Canine Gall-bladder
Authors: Pozo M J , Salido M D , Madrid J A , Salido G M 
Published: April 2011

Abstract
The action of pirenzepine as an antimuscarinic drug has been investigated on motor responses of muscle strips in the canine gall-bladder. Pirenzepine was further used to examine whether gall-bladder motor responses to synthetic sulphated cholecystokinin octapeptide (CCK-8) are sensitive to pirenzepine. Pirenzepine (10−9-10−5 M) antagonized muscle contractions in response to acetylcholine (10−9-10−2 M) and CCK-8 (10−11-10−6 M) in a significant manner. These findings indicate that pirenzepine is a potent antagonist of two substances that are the principal contractile mediators of gall-bladder contraction and suggest that long-term administration of pirenzepine could contribute to stasis of the gall-bladder.
The Actions of Fenfluramine and Interaction with 5-HT3 Receptor-Antagonists to Inhibit Emesis in the Ferret
Authors: Costall Brenda , Naylor Robert J , Tattersall F David 
Published: April 2011

Abstract
The racemate and (+)- and (-)-isomers of fenfluramine (5 mg kg−1 i.p., 1 h pretreatment) antagonized cisplatin-induced retching and vomiting in the ferret. The intravenous injection of (±)-fenfluramine administered on an established cisplatin-induced emesis antagonized the response within minutes of injection. The administration of a lower dose of (±)-fenfluramine (10 mg kg−1 i.p., 1 h pretreatment) failed to antagonize cisplatin-induced emesis when administered alone but enhanced the antiemetic effects of metoclopramide and ICS 205–930. This pretreatment with (±)-fenfluramine failed to enhance the antiemetic effects of zacopride. It is considered that an action of the racemate on presynaptic 5-HT/catecholaminergic systems to reduce neurotransmitter release may enhance the action of certain 5-HT3 receptor antagonists in controlling emesis induced by cisplatin.
Effects of Cularine and Other Isoquinoline Alkaloids on Guinea-pig Trachea and Human Bronchus
Authors: Candenas M L , Naline E , D'Ocón M P , Cortes D , Advenier C 
Published: April 2011

Abstract
The relaxant effects of the isoquinoline alkaloids, cularine, antioquine, obaberine and 6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, with structures related to that of papaverine, have been studied on the guinea-pig isolated trachea and human bronchus against contractions induced by acetylcholine (ACh), histamine, neurokinin A (NKA) and KCl. These effects were compared with those of papaverine and theophylline. Among the alkaloids tested, the most potent was cularine, the relaxant activity of which, in terms of pD2, was between those of papaverine and theophylline. The results showed that for the guinea- pig isolated trachea and the human bronchus, the cularine concentrations required to inhibit K+-induced contractions were close to those necessary to counteract ACh-, histamine- and NKA-induced contractions. The relaxant activity of cularine was not modified when it was tested on tracheal preparations under resting tone or after epithelium removal. In addition, cularine was able to inhibit Ca2+-induced contractions in a Ca2+-free, K+-enriched solution at the same concentrations as those which inhibited the action of the different contractile agents in normal K rebs solution. All these data show that cularine displays non-specific antispasmogenic activity on guinea-pig and human airways. The lower relaxant activity (pD2) of cularine compared with papaverine suggests the importance of free rotation of the isoquinoline-benzyl ring linkage as well as of the degree of hydrogenation of the heterocyclic ring in the spasmolytic effects of isoquinoline compounds.
Cephalosporin C acylase in the autolysis of filamentous fungi
Authors: Reyes F , Martinez M J , Alfonso C , Copa-Patiño J L , Soliveri J 
Published: April 2011

Abstract
Cephalosporin C acylase activity was studied using fluorescamine determination of free — NH2 groups produced in the deacylation of cephalosporin C by the enzyme. Fourteen fungi from different genera were studied and low extracellular cephalosporin C acylase activity was found in the genera Aspergillus, Fusarium and Penicillium. Forty one fungi of these genera were checked but not all presented acylase activity. The enzyme was generally found to be an extracellular enzyme and during the process of autolysis its activity increased with incubation time and with increasing pH of the medium. In no case was β-lactamase activity detected. Penicillium rugulosum and Penicillium griseofulvum were identified as good cephalosporin C acylase producers. Deacetyl esterase activity was also detected in these fungi.
Inhibitory effects of catecholamines on cholinergically and non-cholinergically mediated contractions of guinea-pig isolated bronchial muscle
Authors: Kamikawa Yuichiro , Shimo Yasuo 
Published: April 2011

Abstract
The actions of catecholamines on the responses evoked by electrical field stimulation or by acetylcholine and substance P in guinea-pig bronchial strip chain have been examined. Electrical field stimulation evoked a biphasic contraction, consisting of a cholinergically-mediated fast contraction followed by a non-cholinergically-mediated slow contraction. All catecholamines tested caused a concentration-dependent reduction in the height of the biphasic contraction, where non-cholinergic contractions were more potently inhibited. The inhibitory effect of isoprenaline was largely prevented by propranolol (2 μM) alone, whereas those of noradrenaline and adrenaline were prevented by treatment with both propranolol (2 μM) and yohimbine (2 μM). The inhibitory effect of dopamine was unaffected either by propranolol (2 μM), yohimbine (2 μM) or haloperidol (10 μM). Submaximal contractions of bronchial muscle evoked by exogenous acetylcholine (2 μM) or substance P (0.2 μM) were also inhibited by catecholamines, except dopamine, but the effects were antagonized by propranolol (2 μM) alone. The results suggest that in guinea-pig isolated bronchial muscle, catecholamines can inhibit both cholinergic and non-cholinergic excitatory neurotransmissions not only by postjunctional β-adrenoceptors but also by prejunctional α2-adrenoceptors.
Effect of nicardipine on the relationship of renal blood flow and of renal vascular resistance to perfusion pressure in dog kidney
Authors: Ogawa Nobuyuki 
Published: April 2011

Abstract
The effect of nicardipine, a Ca channel blocker, on autoregulation of renal blood flow and perfusion pressure-vascular resistance relationship has been investigated in perfused kidneys of anaesthetized dogs. In control animals excellent autoregulation of renal blood flow and pressure-dependent elevation of vascular resistance were observed above 100 mmHg of perfusion pressure. However, intra-arterial infusion of nicardipine at doses of 3 and 10 μg min−1 showed dose-dependent impairment of the autoregulatory response and of elevation of vascular resistance. Infusion of nicardipine (2.5 μg min−1) into the renal artery also inhibited renal vasoconstriction induced by YC-170, a Ca channel activator. These results suggest that the inhibitory effect of nicardipine upon renal autoregulation may be due to its Ca2+ channel blocking action.
Kinetics of the Intestinal Uptake of Zinc Acexamate in Normal and Zinc-depleted Rats
Authors: Torres-Molina F , Martínez-Coscollá A , Gisbert S , Quintana E , Sendrós S , Peris-Ribera J E , Plá-Delfina J M 
Published: April 2011

Abstract
The uptake of zinc as acexamic acid salt in the small intestine of the anaesthetized rat was shown to be a two-phase process in normal animals. The first phase is rapid mucosal binding which satisfies the Freundlich isotherm equation and which involves about 30 per cent of the initially perfused zinc. The second phase was characterized as an apparent absorption step which obeys Michaelis-Menten and first-order combined kinetics, with the following parameters: Vm = 6.51 mg h−1; Km = 2.96 mg; ka = 0.306 h−1. In largely non-saturated conditions, an apparent global rate constant of about 2.50 h−1 was calculated. No significant interference due to endogenous zinc excretion into the small intestine was observed during the absorption period. In zinc-deficient animals, the two phases were not so well characterized. Binding was non-linear and apparent absorption efficiency was much greater at high zinc concentrations, so no evidence of saturable kinetics was found, thus confirming the hypothesis of a homeostatic zinc regulation mechanism.
Differential Influence of Laboratory Anaesthetic Regimens upon Renal and Hepatosplanchnic Haemodynamics in the Rat
Authors: Gumbleton Mark , Nicholls Paul J , Taylor Glyn 
Published: April 2011

Abstract
Renal blood flow in rats anaesthetized with the combination alphaxolone/alphadolone (3.90 mL min−1 (g tissue)−1) was significantly (P &lt; 005) greater than in rats anaesthetized with ketamine/midazolam (3.24 mL min−1 (g tissue)−1), pentobarbitone (3.19 mL min−1 (g tissue)−1), fentanyl/fluanisone/midazolam (2.84 mL min−1 (g tissue)−1) or urethane (1.99 mL min−1 (g tissue)−1). Renal blood flow in the urethane anaesthetized rats was significantly (P &lt; 0.05) lower than in animals anaesthetized with the other anaesthetic regimens, and is consistent with literature reports of a depressive effect of urethane anaesthesia upon xenobiotic renal clearance in the rat. Hepatosplanchnic blood flow was highest in the alphaxolone/alphadolone anaesthetized animals (71.7 mL min−1 kg−1), with the urethane anaesthetized animals demonstrating a significantly (P &lt; 0.05) lower (33.4 mL min−1 kg−1) blood flow. The fentanyl/fluanisone/midazolam (65.4 mL min−1 kg−1), pentobarbitone (61.1 mL min−1 kg−1), and ketamine/midazolam (51.4 mL min−1 kg−1) regimens resulted in hepatosplanchnic blood flows of intermediate magnitude. The observed marked differential effects of the anaesthetic regimens upon renal and hepatosplanchnic blood flows may dramatically influence drug disposition in the experimental animal, and be of significance to laboratory pharmacokinetic studies in which anaesthesia is used.
Gonadal Influence on the Metabolism and Haematological Toxicity of Dapsone in the Rat
Authors: Coleman M D , Tingle M D , Winn M J , Park B K 
Published: April 2011

Abstract
Administration of dapsone (33 mg kg−1) to intact rats resulted in a marked elevation of methaemoglobin levels in male (435.0 ± 105.2% met Hb h) compared with female rats (59.0 ± 17.2% met Hb h). However, the clearance of dapsone was significantly faster in males compared with females. Female rats showed very low levels of methaemoglobin which were accompanied by significantly higher blood concentrations of parent drug. Clearance of dapsone in castrated animals was less than one-third of that of the intact sham-operated males (252.2 ± 67.2 vs 81.4 ± 33.0 mL h−1). Likewise, clearance of dapsone in ovarectomized rats was approximately half that of intact females. There were no significant differences in the disposition of dapsone between the ovarectomized (AUC, 431.0 ± 31.7 μg h mL−1; t 1/2, 15.62 ± 1.8 h) and castrated (AUC, 450.6 ± 150.9 μg h mL−1; t 1/2, 17.6 ± 7.9 h) animals. However, methaemoglobin levels in castrated males, although less than a third of those of intact males, significantly exceeded those of ovarectomized animals. There was no significant difference between the four groups of animals with respect to red cell sensitivity to the methaemoglobin-forming capacity of the toxic metabolite of dapsone, the hydroxylamine. Metabolic conversion of dapsone to the hydroxylamine in the presence of NADPH was 7.6 ± 1.5% for liver microsomes from intact males and was significantly greater (P &lt; 0.05) than the corresponding values for liver microsomes from castrated rats (5.3 ± 0.59%). Conversion of dapsone to dapsone-NOH by liver microsomes from intact females and ovarectomized animals was below 1 % in both cases. This study illustrates the androgenic control of N-hydroxylation in the rat.