bluuebunny/crossref_metadata_2025_split huggingface dataset:
The inotropic effect of ouabain and its antagonism by dihydroouabain in rat isolated atria and ventricles in relation to specific binding sites
Authors: Finet M. , Godfraind T. , Noel F. 
Published: July 2012

The inotropic effect of ouabain has been studied in rat ventricles and atria.
The concentration‐effect curve of ouabain may be fitted by a model assuming the existence of two saturable components. The component with the higher sensitivity to ouabain accounted for 30% of the maximal increase in systolic tension in ventricles and for only 5% in atria. Increase in diastolic tension was only apparent at ouabain concentrations required to observe the low sensitivity component.
[3H]‐ouabain binding has been examined in microsomes prepared from atria and ventricles. High and low affinity binding sites have been observed. The ratio of high and low affinity ouabain binding sites was 4 fold lower in microsomes from rat atria than from rat ventricles. This could account for the difference in the response of these two tissues to the inotropic action of ouabain.
In ventricular strips the high sensitivity component was much less apparent in the presence of dihydroouabain than with ouabain.
When ventricular strips were preincubated in the presence of dihydroouabain 3 μm, the increase in systolic tension evoked by ouabain 1 μm was significantly reduced. Cumulative concentration‐effect curve studies showed dihydroouabain antagonism to the high sensitivity component.
Antinociceptive action of nicotine and its methiodide derivatives in mice and rats
Authors: Aceto Mario D. , Awaya Hiroyoshi , Martin Billy R. , May Everette L. 
Published: July 2012

Three quaternary methiodides of nicotine were prepared and tested for antinociceptive activity in the mouse tail‐flick, mouse phenylquinone and rat tail‐flick tests.
Following peripheral administration, all three methiodides were inactive in the mouse and rat tail‐flick procedures, whereas nicotine was active in both tests, which suggested that nicotine was acting centrally.
Quaternization of nicotine did not eliminate antinociceptive activity as demonstrated by the intraventricular injection of the methiodides in mice. Nicotine pyrrolidine and bis methiodides were somewhat more potent than nicotine, whereas nicotine pyridine methiodide was considerably less potent than nicotine in the tail‐flick procedure.
Systemically administered nicotine pyrrolidine methiodine was approximately one‐third as active as nicotine in the mouse phenylquinone test; nicotine pyridine methiodide and nicotine bis methiodide were 100 and 300 times less active, respectively.
Hexamethonium partially blocked nicotine and nicotine pyrrolidine methiodide, whereas mecamylamine blocked nicotine completely but nicotine pyrrolidine methiodide partially. Nicotine may have both central and peripheral actions in the mouse phenylquinone test, whereas nicotine pyrrolidine methiodide may have both nicotine and non‐nicotine like antinociceptive activity.
The radiolabeled methiodides were synthesized and their disposition in body tissues studied. The methiodides were found to penetrate brain poorly (plasma‐to‐brain ratios > 20).
The methiodides were metabolized to nicotine to a small extent. This metabolism occurred to a greater extent in mice than in rats.
Evidence for a magnesium‐sparing action by amiloride during renal clearance studies in rats
Authors: Devane John , Ryan Michael P. 
Published: July 2012

The potassium‐sparing diuretic, amiloride, reduced the fractional excretion of magnesium in anaesthetized rats.
Alterations in glomerular filtration rate (GFR), the filtered load of magnesium, arterial blood pressure, the status of the extracellular fluid volume, plasma aldosterone concentration and acid‐base balance were not involved.
It was concluded that amiloride exerted a magnesium‐sparing effect by a direct renal action.
Evidence that 5‐hydroxytryptamine in the forebrain is involved in naloxone‐precipitated jumping in morphine‐dependent rats
Authors: Cervo L. , Romandini S. , Samanin R. 
Published: July 2012

A withdrawal syndrome was precipitated by naloxone in morphine‐dependent rats injected with 5,7‐dihydroxytryptamine (5,7‐DHT) in the ventromedial tegmentum (VMT) at the level of the nucleus interpeduncularis.
5,7‐DHT, which markedly depleted 5‐hydroxytryptamine (5‐HT) in the forebrain but not in the brainstem, significantly reduced jumping in abstinent rats with no significant effect on other withdrawal signs.
The effect of morphine 10 mg kg−1 on responses on the hot plate was unchanged in 5,7‐DHT‐treated rats.
The findings suggest that 5‐HT in the forebrain is selectively involved in the jumping of morphine‐abstinent rats.
The effect of indomethacin on the contractile response of the guinea‐pig lung parenchymal strip to leukotrienes B4, C4, D4 and E4
Authors: Austen K.F. , Corey E.J. , Drazen J.M. , Leitch A.G. 
Published: July 2012

Indomethacin (1 μg ml−1) almost totally inhibited the dose‐dependent contractile response of isolated lung parenchymal strips of the guinea‐pig (GPLS) to leukotriene B4 (LTB4) over the concentration range 0.18–18 nM.
LTC4 (0.63 pM‐63 nM)‐induced contractions of GPLS were not significantly inhibited by indomethacin (1.0 and 10.0 μg ml−1) except when the highest LTC4 concentration (63 nM) was tested in the presence of indomethacin (10 μg ml−1).
LTD4 (1.3 fM‐13 nM)‐induced contractions of GPLS were not significantly inhibited by indomethacin (0.1–10 μg ml−1) except for contractions induced by concentrations of LTD4 greater than 0.13 nM and 13 nM. Indomethacin 1 μg ml−1 and 10 μg ml−1 inhibited the contractile response to 13 nM LTD4 by 37 and 16% respectively.
LTE4 (2.3 fM‐23 nM)‐induced contractions of GPLS were not significantly inhibited by indomethacin (0.1–10 μg ml−1). Contraction due to LTE4 23 pM was significantly potentiated by indomethacin (1 μg ml−1).
Clotrimazole (10 μM) significantly inhibited LTD4‐induced contractions of GPLS at concentrations greater than 13 pM but had no significant effect on LTC4‐induced contractions.
Cyclo‐oxygenase products, probably principally thromboxane A2, are important secondary mediators of LTB4‐induced contractions of GPLS but make little or no contribution to contractions of GPLS induced by LTC4, LTD4, and LTE4, except at higher concentrations of LTD4 and possibly LTC4. Certain concentrations of LTE4 may generate bronchodilator PGE2 in GPLS.
The effect of exaprolol (MG 8823) on epicardial ST‐segment changes in a feline model of acute myocardial ischaemia
Authors: Parratt J.R. , Udvary Eva 
Published: July 2012

A model is described (anaesthetized, open‐chest cats subjected to acute coronary artery occlusion) which allows the effects of drug interventions to be determined on one major electrocardiographic index of myocardial ischaemia. Epicardial ST‐segment changes were continuously recorded from five individual sites on the surface of the left ventricle.
Coronary artery occlusion (left anterior descending branch) resulted in marked and consistent elevations of the ST‐segment in all sites in nearly all experiments. These changes started within 1 min of the onset of ischaemia and reached a peak at between 30 and 60 min; thereafter there was a gradual reduction over the next 4 h. The one significant haemodynamic effect of coronary artery occlusion was an increase in left ventricular (LV) end‐diastolic pressure (LVEDP). Ventricular ectopic activity was not pronounced in this model (about 50 ectopic beats over the initial 30 min post‐occlusion period).
Exaprolol (1.0 mg kg−1, intravenously) a potent β‐adrenoceptor blocking agent with ‘membrane stabilising activity’, when given 1 h after the onset of ischaemia, reduced heart rate and LV dP/dtmax and increased LVEDP. These effects were prolonged (i.e. little recovery in heart rate 3 h after administration).
Exaprolol decreased total ST‐segment elevation immediately after administration; this was significantly different from the effect of intravenous saline and lasted for at least 3 h. The effects appeared to be greater at sites of less pronounced ischaemia.
Intramyocardial temperature records were taken to indicate a reduction in blood flow to the ischaemic region; however the alleviation of epicardial ST‐segment elevation suggests an improved myocardial oxygen demand:supply ratio.
Reperfusion was unsuccessfully attempted after a 4 h occlusion period; reperfusion after a shorter period (30 min) resulted in ventricular ectopic activity but no fibrillation.
Effects of yohimbine, rauwolscine and corynanthine on contractions and calcium fluxes induced by depolarization and prostaglandin F2α in rat aorta
Authors: Godfraind T. , Miller R.C. , Lima J. Socrates 
Published: July 2012

The effects of the selective α2‐adrenoceptor antagonists yohimbine and its stereo‐isomer rauwolscine and the selective α1 ‐adrenoceptor antagonist corynanthine (a third yohimbine stereoisomer) on contractions induced in rat aorta by depolarization and prostaglandin F2α (PGF2α) have been compared.
In calcium‐free solution, depolarization with 100 mM K+ failed to produce a contraction of rat aorta but PGF2α (3 μM) stimulated a contraction equal to about 23% of maximal elicited in normal physiological solution.
Yohimbine had no significant effect on depolarization‐induced contractions except at concentrations greater than 30 μM. Rauwolscine and corynanthine (1 to 100 μM) depressed depolarization‐induced contractions in a concentration‐dependent manner, but the characteristics of inhibition were not identical.
Contractions induced by PGF2α (3 μM) were depressed in a concentration‐dependent manner by rauwolscine (3 to 100 μM) but were unaffected by yohimbine or corynanthine.
Depolarization‐stimulated 45Ca influx was depressed by rauwolscine and corynanthine to about the same extent as were the contractions; while rauwolscine (100 μM) completely inhibited PGF2α‐stimulated 45Ca influx, it also depressed part of the PGF2α‐stimulated contraction dependent on intracellular calcium.
Rauwolscine (100 μM) partly inhibited PGF2α‐stimulated release of 45Ca from aortic smooth muscle in calcium‐free solution.
It is concluded that the yohimbine structure possesses a calcium entry blocking action as well as a depressant action on contractions not dependent on calcium entry. The predominant effect depends on the structural configuration and the nature of the stimulating agent.
The effects of p‐chloromercuribenzoate on muscarinic receptors in the cerebral cortex
Authors: Birdsall N.J.M. , Burgen A.S.V. , Hulme E.C. , Wong E.H.F. 
Published: July 2012

The action of p‐chloromercuribenzoate (PCMB) on the ligand binding properties of the muscarinic receptors in the rat cerebral cortex has been examined.
At low concentrations, PCMB produces a selective change in the binding of agonists without any effect on the binding of antagonists.
At higher concentrations, the structure‐binding profile for binding antagonists is changed. The affinity of agonists is greatly reduced and the heterogeneity of binding eliminated.
The effects of both high and low concentrations of PCMB can be reversed by dithiothreitol.
Inactivation of receptors proceeds in parallel and is kinetically complex. It can only be partially reversed by dithiothreitol.
Evidence is presented connecting the low affinity agonist binding site with the high affinity pirenzepine binding site.
The changes produced by PCMB have been interpreted in terms of the modification of receptor conformation.
Pharmacological characterization of a substance P antagonist, [D‐Arg1, D‐Pro2, D‐Trp79, Leu11]‐substance P
Authors: Watson Stephen P. 
Published: July 2012

The substance P antagonist [D‐Arg1, D‐Pro2, D‐Trp7,9, Leu11]‐substance P produced parallel log dose‐response curve shifts to both substance P and eledoisin on five in vitro smooth muscle preparations.
The slope values of Arunlakshana‐Schild plots were not significantly different from unity suggesting that it acts as a simple competitive antagonist on all five preparations with an association constant (Ka) in the range of 0.3–1.5 × 106M−1.
The Ka value of the antagonist was always slightly greater when tested against eledoisin than against substance P; however, this difference appears too small to suggest that these two agonists are acting on different receptor sub‐types.
Effects of baclofen on synaptically‐induced cell firing in the rat hippocampal slice
Authors: Ault Brian , Nadler J. Victor 
Published: July 2012

The effects of baclofen on the synaptically‐induced firing of pyramidal and granule cell populations were tested in the rat hippocampal slice. Population spikes were evoked by stimulating excitatory pathways in the presence and absence of bath‐applied drug.
(±)‐Baclofen (20 μM) completely blocked the firing of CA1 or CA3 hippocampal pyramidal cells subsequent to stimulation of projections that originate in area CA3. In contrast, the firing of dentate granule cells evoked by stimulation of the perforant path fibres was depressed by only 46% and baclofen did not affect the monosynaptic firing of CA3 pyramidal cells evoked by mossy fibre stimulation. These results are consistent with the effects of baclofen on the corresponding extracellularly‐recorded excitatory postsynaptic potentials (e.p.s.ps).
The Schaffer coUateral‐commissural population spike in area CA1 was depressed by (−)‐baclofen (EC50 = 2.8 μM), GABA (EC50 = 2.2 mM) and 3‐aminopropanesulphonic acid (3‐APS) (EC50 = 0.34 mM). (−)‐Baclofen was 180 times as potent as (+)‐baclofen.
Bicuculline methiodide (100 μM) did not reverse the depressant action of (−)‐baclofen. GABA‐induced depressions were antagonized to only a small degree, whilst the effect of 3‐APS was readily reversed. Raising the concentration of bicuculline from 100 μM to 500 μM did not further reverse the action of GAB A.
The effects of (−)‐baclofen and 3‐APS on the relationship between extracellular e.p.s.p. and population spike were tested by stimulation of the Schaffer collateral‐commissural fibres in area CA1. (−)‐Baclofen shifted the ‘input/output’ curve to the right at a concentration of 1 μM, but less or not at all at 3 μM. In contrast, increasing the concentration of 3‐APS shifted this curve farther to the right.
These results are consistent with the hypothesis that baclofen and GAB A can depress neuronal firing by interacting with a bicuculline‐insensitive receptor. In the CA1 area, activation of these receptors mainly depresses transmitter release from terminals of projections from area CA3, but also reduces pyramidal cell excitability.
The effects of benzodiazepine agonists, inverse agonists and Ro 15–1788 on the responses of the superior cervical ganglion to GABA in vitro
Authors: Little H.J. 
Published: July 2012

The effects of benzodiazepines and their antagonists on the responses to γ‐aminobutyric acid (GABA) of the superior cervical ganglion of the rat were examined using extracellular recording.
Chlordiazepoxide (1 μm to 28.9 μm) and flurazepam (145–725 nm) increased the responses of the ganglion to GABA and the increases were antagonized by Ro 15–1788, at 3.34 μm. The concentration of GABA used was 9.7 μm which gave half‐maximal responses.
Chlordiazepoxide similarly increased the responses of the ganglion to GABA 38.8 μm in the presence of bicuculline 27.2 μm. This concentration of GABA gave, with bicuculline, responses of a similar magnitude as those to 9.7 μm in the absence of bicuculline. Bicuculline did not affect the actions of chlordiazepoxide or the antagonism by Ro 15–1788.
Ro 15–1788 did not affect the increases in GABA response caused by pentobarbitone or by phenobarbitone in the presence of bicuculline.
Ethyl β‐carboline‐3‐carboxylate (βCCE) (207 nm to 1 μm) significantly decreased the responses to GABA in the presence and in the absence of bicuculline. The decreases were antagonized by Ro 15–1788 (3.34 μm). βCCE at 2.1 μm and above did not significantly change the responses to GABA.
Methyl β‐carboline‐3‐carboxylate (βCCM) at 88 to 440 nm significantly decreased the responses to GABA. The decreases were antagonized by Ro 15–1788 (3.34 μm) and were also seen in the presence of bicuculline.
High concentrations of Ro 15–1788 decreased the responses to GABA, 9.7 μm, but increased the responses to GABA 38.8 μm in the presence of 27.2 μm bicuculline.
The pattern of effects of the benzodiazepines, β‐carbo lines and low doses of Ro 15–1788 on the responses to GABA was similar to the effects of these compounds on seizure threshold and anxiety‐related behaviour in vivo.
Development of markers for cholinergic neurones in re‐aggregate cultures of foetal rat whole brain in serum‐containing and serum‐free media: effects of triiodothyronine (T3)
Authors: Atterwill C.K. , Kingsbury A. , Nicholls J. , Prince A. 
Published: July 2012

Development has been studied in re‐aggregate cultures derived from the 16 day foetal rat brain and the effects of triiodothyronine (T3) investigated. Cultures were maintained in either a medium containing 10% serum (S+), or in serum‐free culture medium (S−) or in serum‐free medium containing 30nm T3.
The muscarinic cholinoceptor, measured by specific binding of [3H]‐quinuclidinyl benzitate ([3H]‐QNB) at 9 and 14 days in vitro, was at a lower level in the serum‐free cultured cells compared with those in serum‐containing culture medium (S+). In cultures in the latter medium, receptor concentration at day 14 was of a similar magnitude to that in rat brain at an equivalent postnatal age. Binding increased with development from 9 to 14 days in vitro in the S+ medium but not in the S− medium. T3 treatment caused an 85% increase in [3H]‐QNB binding compared with the cultures in S− medium at day 14 to a level equivalent to that found in the cells grown in S+ medium. This increase was reflected in the Bmax but not in the KD (approx. 0.1 nm).
Choline acetytransferase (ChAT) activity developed more slowly in the S− medium than in the S+ medium where the specific activity approximated values obtained in vivo. T3 treatment of cultures grow in S− medium significantly enhanced the developmental rate of increase of ChAT activity.
The characteristics of [3H]‐choline uptake and metabolism in the cultures was examined. Uptake was strictly Na+‐independent but was energy‐dependent, and inhibited by 2, 4′‐dinitrophenol (2, 4′‐DNP) and cooling (0–4°C). Neither iodoacetate nor ouabain had any effect on the amount of uptake. Hemicholinium (HC3) was a potent inhibitor of uptake (70% inhibition at 10 μm HC3). Metabolism studies showed virtually no conversion to [3H]‐acetylcholine ([3H]‐ACH) in re‐aggregates grown in either the S+, S− or T3 containing media. However, a small amount of [3H]‐choline was incorporated into phosphorylcholine. T3 treatment had no effect on this metabolic profile.
The kinetics of [3H]‐choline uptake by the re‐aggregates was also studied in the re‐aggregate cultures (after 12 and 22 days in vitro) using [3H]‐choline at 0.05–100 μm. Both Eadie‐Hofstee transformation and least‐squares analysis of the data showed that the uptake comprised only a single low‐affinity component with an apparent Kt = approx. 50 μm. Unlike ChAT and [3H]‐QNB binding, there appeared to be no difference between the uptake in the different culture conditions.
It is concluded that the differentiation of cholinergic neurones and muscarinic receptors in serum‐free cultured re‐aggregates from foetal rat brain is enhanced by thyroid hormone treatment. The development of [3H]‐choline uptake does not seem to be associated with cholinergic cells under these culture conditions, and is unaffected by thyroid hormone treatment.
Lack of a causal relationship between the vasodilator effect of papaverine and cyclic AMP production in the dog basilar artery
Authors: Fujioka Masahiko 
Published: July 2012

The effects of papaverine and isoprenaline on smooth muscle cells of the dog basilar artery were investigated using radioimmunoassay, electrophysiological and isometric tension recording methods. For comparative purposes, the actions of these drugs on the guinea‐pig basilar artery were also examined.
Papaverine and isoprenaline (1 μm and 10 μm) increased the amount of cyclic AMP in both dog and guinea‐pig basilar arteries.
Papaverine (up to 100 μm) and isoprenaline (up to μm) had no effect on the membrane potential and membrane resistance measured by recording the amplitudes of the electrotonic potentials in smooth muscle cells of the dog and guinea‐pig basilar arteries.
The action potential evoked by outward current pulses after pretreatment with tetraethylammonium chloride (5–10 mm) was inhibited by papaverine (>1 μm) but not by isoprenaline (up to 10 μm) in smooth muscle cells of the dog and guinea‐pig basilar arteries.
In the dog basilar artery, papaverine (>1 μm) consistently inhibited the contractions evoked by excess concentrations of [K]o (>20.2 mm) or 5‐hydroxytryptamine (10 nm‐10 μm), dose‐dependently. Isoprenaline (1 μm) had only slight effects on the contraction evoked by low concentrations of 5‐hydroxytryptamine (10 nm).
In the Ca2+‐free solution containing EGTA (2 mm), the contraction evoked by 5‐hydroxytryptamine (10 μm) or caffeine (10 mm) was dose‐dependently inhibited by papaverine (>1 μm). However, isoprenaline (1 μm) had no effect on these contractions.
These results indicate that the vasodilator actions of papaverine on the dog basilar artery are mainly due to inhibition of the voltage‐dependent influx of Ca2+ and also to inhibition of the receptor‐activated release of Ca2+ stored in the cell. Since isoprenaline increased the cyclic AMP to the same extent as papaverine but had no effect on the electrical and mechanical responses, the inhibitory actions of papaverine on this tissue may not be causaly related to the increased levels of cyclic AMP induced by inhibition of phosphodiesterase.
Influence of protein‐calorie malnutrition on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats
Authors: Varma D.R. , Yue T.L. 
Published: July 2012

The influence of protein‐calorie malnutrition (PCM) on the pharmacokinetics, transplacental passage and tissue localization of dexamethasone was determined in Sprague‐Dawley rats.
PCM increased the plasma half‐life and volume of distribution of dexamethasone in pregnant but not in nonpregnant rats.
Ratios of foetal to maternal serum dexamethasone concentrations were 0.2–0.4 at different dose levels (0.8–20 μmol kg−1), time intervals (0.25–12 h) and gestational ages (day 14–21).
PCM increased the foetal serum and tissue concentrations of dexamethasone but exerted no significant effect on its binding to maternal and foetal serum proteins or on its metabolism by the placenta.
It is suggested that significantly lower foetal than maternal serum levels of dexamethasone are due to efficient elimination of this agent by the foeto‐placental unit and an impairment of this mechanism may account for the observed increase in dexamethasone levels in the foetuses of PCM rats.
Influence of streptozotocin‐diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats
Authors: Mulay S. , Varma D.R. 
Published: July 2012

The influence of streptozotocin‐diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone was determined in Sprague‐Dawley rats.
Diabetes significantly increased the volume of distribution of dexamethasone in pregnant but not in nonpregnant rats; plasma half‐life was not significantly increased.
Concentrations of maternally administered dexamethasone in all tissues studied (maternal and foetal serum and livers, foetal lungs and placentas) except the amniotic fluid were lower in diabetic than in control animals.
Diabetes did not alter the binding of dexamethasone to maternal or foetal serum proteins.
Insulin treatment partially reversed the effects of diabetes on the maternal‐foetal exchange of dexamethasone.
Diabetes‐induced decrease in the foetal localization of dexamethasone appears to be caused by a decrease in the maternal serum levels as well as by an increase in the foetal excretion of the steroid into the amniotic fluid.
In so far as the rat model reflects the human situation, the present data suggest that a standard dose of dexamethasone might not be adequate in promoting foetal lung maturation in diabetic pregnancies.