bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of inorganic nitrite in methaemoglobin formation after nitrate ester administration to the rat
Authors: CLARK D. G. , LITCHFIELD M. H. 
Published: July 2012

Summary
Methaemoglobin is rapidly formed during the incubation of rat red cells with inorganic nitrite, whereas ethylene glycol dinitrate at a higher concentration has little effect.
The concentrations of blood inorganic nitrite in the rat after ethylene glycol dinitrate or glyceryl trinitrate injection can be reproduced by the infusion of nitrite. The methaemoglobin formed after ethylene glycol dinitrate or glyceryl trinitrate injection is equivalent to that produced from nitrite infusions simulating its formation from the nitrate esters.
It is concluded that methaemoglobin arising from nitrate ester administration is formed principally by the action of the metabolite inorganic nitrite.
A comparative study of some convulsant substances as γ‐aminobutyric acid antagonists in the feline cerebral cortex
Authors: HILL R. G. , SIMMONDS M. A. , STRAUGHAN D. W. 
Published: July 2012

Summary
By the use of microiontophoretic techniques, quantitative estimates were obtained of the depressant effects of γ‐aminobutyric acid (GABA) on single feline cortical neurones.
Picrotoxin, bicuculline, strychnine, (+)‐tubocurarine, penicillin and leptazol were also applied microiontophoretically to single neurones. Sequential GABA applications were made before, during and after the microiontophoresis of these substances and any effects on the time course of the GABA depression were measured as an estimate of antagonism or potentiation of GABA.
(+)‐Tubocurarine was found to be a potent GABA antagonist. Picrotoxin and bicuculline were rather less potent and strychnine and penicillin only weakly active as GABA antagonists. Leptazol appeared to be inactive against GABA depressions.
In addition, bicuculline and strychnine were found to be capable of potentiating the depressant action of GABA. This property was not shared by the other substances studied.
All the substances studied produced changes in neuronal firing rate that did not correlate with GABA antagonism.
In conclusion, several potent convulsants have been shown to be capable of GABA antagonism. It is not yet clear that this effect, rather than a direct effect on neuronal excitability, is the prime mechanism behind their convulsant properties.
The influence of histamine and other vasoactive substances on contractile responses of cat skeletal muscle to acetylcholine
Authors: BLOCK A. J. , REIT E. 
Published: July 2012

Summary
The effect of vasoactive substances, chiefly histamine, on contractions of cat skeletal muscle evoked by acetylcholine has been studied. For this purpose all of these agents were administered intra‐arterially to anterior tibialis, chiefly, and also to soleus and external rectus muscles in vivo.
Under these conditions, histamine itself never altered the resting tension of the muscle, but always enhanced the increase in tension produced by acetylcholine injected shortly afterward.
On the anterior tibialis muscle, it was determined that the threshold potentiating dose of histamine was 0·001 μg/kg, and that maximal enhancement occurred when 0·1 μg/kg was injected 15 s before fixed, submaximal doses of acetylcholine. Injected 15 s before graded doses of acetylcholine, histamine 0·1 μg/kg shifted the acetylcholine dose‐response curves approximately 1·5 log units to the left.
Under similar experimental conditions the vasodilator, bradykinin, 0·001–1 μg/kg, and procedures which produce a local increase in nutritive capillary blood flow also enhanced acetylcholine‐evoked contractile responses of the anterior tibialis, whereas the vasoconstrictor, angiotensin, 0·001–1 μg/kg, inhibited them.
The potentiating effect of histamine was antagonized by mepyramine, but was undiminished by denervation of the muscle either acutely or for 4 days.
Histamine failed to enhance responses of the muscle to electrical stimulation of either the muscle, directly, or its motor nerve.
Histamine also had no effect upon acetylcholine‐evoked responses of the isolated external rectus muscle in vitro.
It is suggested that the potentiating effect of histamine in vivo is due to its vasodilator action within the muscles which, by relaxing arterioles and precapillary sphincters, could allow more of the blood‐borne acetylcholine to reach more of its receptors on the muscle fibres in a given time.
Prostaglandins and the mechanism of analgesia produced by aspirin‐like drugs
Authors: FERREIRA S. H. , MONCADA S. , VANE J. R. 
Published: July 2012

Summary
Resting splenic venous outflow from anaesthetized dogs contains prostaglandin‐like material: the concentration increases after intra‐arterial injections of bradykinin into the spleen, and is abolished by treatment with indomethacin.
Intra‐arterial injections of bradykinin into the spleen of lightly anaesthetized dogs elicit a dose‐dependent reflex increase in the blood pressure, which is reduced but not abolished by treatment with indomethacin.
Addition of prostaglandin E1 or E2 either by injections or by infusions restores the reflex increase in the blood pressure due to bradykinin injections after indomethacin treatment.
The sensitizing action of endogenously released prostaglandins at or near the afferent nerve endings is discussed.
The analgesic activity of aspirin‐like drugs is explained in terms of the removal of the sensitizing activity of prostaglandins.
Cellular localization of the uptake of 5‐hydroxytryptamine in the area postrema of the rabbit after injection into a lateral ventricle
Authors: DOW R. C. , LASZLO I. , RITCHIE ISOBEL M. 
Published: July 2012

Summary
The cellular localization of 5‐hydroxytryptamine (5‐HT) was investigated in the area postrema of the rabbit after intraventricular injection under different experimental conditions.
5‐HT was found to be acccumulated in different parts in and near to the area postrema, e.g. in glial cells, dorsal surface of the area postrema and ependyma of the central canal.
The concentrations of 5‐HT and 5‐hydroxy indol‐3‐yl acetic acid (5‐HIAA) were measured in different parts of the brain and CSF in control and in 5‐HT treated animals with and without pargyline pretreatment. Intraventricular injection of 5‐HT increased the concentration of 5‐HT and 5‐HIAA in the brain and in the CSF; pretreatment with pargyline further increased the concentrations of 5‐HT but decreased the concentration of 5‐HIAA.
Mechanism of efflux of noradrenaline from adrenergic nerves in rabbit atria
Authors: PATON D. M. 
Published: July 2012

Summary
The mechanism of efflux of (—)‐[3H]‐noradrenaline was examined in rabbit atria, which were pretreated with reserpine and pargyline.
Between 40 and 100 min, efflux occurred predominantly from a single intraneuronal compartment.
Efflux was rapidy increased by (—)‐ and (+)‐noradrenaline, tyramine and (±)‐metaraminol, but not by (±)‐isopropylnoradrenaline or (±)‐normetanephrine. The increase in efflux produced by (—)‐noradrenaline was inhibited by cocaine and desipramine but not by lidocaine.
Spontaneous effluxes, and those accelerated by (—)‐noradrenaline, were temperature‐sensitive.
Efflux was increased by ouabain, omission of K+, metabolic inhibition and lowering of the external Na+ concentration. These effects were significantly reduced by cocaine and desipramine but not by lidocaine.
These findings provide evidence that the efflux of [3H]‐noradrenaline from adrenergic nerves occurs by a cocaine‐sensitive, carrier‐mediated process. The characteristics of the efflux process are compatible with, but not conclusive proof for, the Na+‐gradient hypothesis.
Some effects of dimethyl sulphoxide (DMSO) on the frog neuromuscular junction
Authors: EVANS M. H. , JAGGARD PAMELA J. 
Published: July 2012

Summary
Dimethyl sulphoxide (DMSO) partially reversed neuromuscular blockade brought about by the action of (+)‐tubocurarine or Mg2+ on the frog sartorius nerve‐muscle preparation.
The amplitude and duration of the endplate potential (e.p.p.) were increased by DMSO at concentrations of 70 mm or greater.
Miniature endplate potentials were raised in frequency, prolonged in duration and increased in amplitude by DMSO at concentrations of 141 mm or greater, but the increase in amplitude was generally less than in the case of the e.p.p.
The resting muscle membrane potential was significantly depolarized by DMSO at 70 mm or greater concentrations, both at the endplate and remote from an endplate.
The reversal of neurmuscular blockade by DMSO can be explained in terms of its previously reported ability to inhibit cholinesterase activity, together with the depolarizing action on muscle.
Blood changes in experimental arthritis in two types of genetically different rats
Authors: EISEN V. , FREEMAN PATRICIA C. , LOVEDAY C. , WEST G.B. 
Published: July 2012

Summary
Rats genetically resistant to dextran and other agents producing the anaphylactoid reaction (NR rats), have a higher polymorph count than do rats which react to these agents (R rats).
NR rats do not develop polyarthritis when a hind paw is injected intradermally with Freund's adjuvant.
The polyarthritis produced by an intravenous injection of Mycoplasma arthritidis culture develops more slowly in NR rats than in R rats.
It is not clear whether the higher polymorph count in NR rats is a main factor in determining their resistance to adjuvant‐induced arthritis.
THE USE OF STEREOTACTIC DISSECTION FOLLOWED BY FLUORIMETRIC ASSAY, TO DETERMINE THE DISTRIBUTION OF NORADRENALINE, DOPAMINE AND 5‐HYDROXYTRYPTAMINE IN THE PREOPTIC HYPOTHALAMIC AREA OF RABBIT BRAIN: AN ALTERNATIVE APPROACH TO HISTOCHEMISTRY
Authors: METCALF G. 
Published: July 2012

A method of stereotactic dissection followed by fluorimetric assay, has been used to determine the distribution of noradrenaline, dopamine and 5‐hydroxytryptamine (5‐HT) within the preoptic hypothalamic area of rabbit brain.
The method involved subdividing the area into a number of thin slices cut with reference to stereotactic co‐ordinates. The amine content of each slice was then determined fluorimetrically.
Noradrenaline was shown to be concentrated (>2.0 μg/g) in two areas within the preoptic hypothalamic area, both of which were adjacent to the mid‐saggittal line: the first was close to the preoptic nucleus and the second immediately caudal to the main group of hypothalamic nuclei.
Dopamine was evenly distributed throughout the preoptic hypothalamic area.
5‐HT was concentrated (>1.6 μg/g) towards the lateral borders of the area, principally in the region which joins the preoptic area to the anterior hypothalamus.
The relative merits of the stereotactic approach and the histochemical approach are discussed.
PLASMA KININ AND KININOGEN LEVELS IN THE FEMALE RAT DURING THE OESTROUS CYCLE, PREGNANCY, PARTURITION AND THE PUERPERIUM
Authors: McCORMICK J.T. , SENIOR JUDITH 
Published: July 2012

Plasma kininogen concentration of the female rat did not change during the oestrous cycle but increased two‐fold during gestation. Plasma kininogen did not change during parturition, rose in the first puerperal day and then rapidly declined to non‐pregnant levels.
Free kinin levels in the blood of non‐pregnant female rats were low and inconstant. Free kinin was undetectable in the blood of pregnant rats, but was found in four out of ten parturient rats.
After administration of the kininase inhibitor dimercaprol (30 mg/kg i.p.), free kinin was present in the blood of six parturient rats. Dimercaprol caused appearance of free kinin in the blood of only one out of six non‐pregnant rats.
It appears that the plasma kinin system is activated to a small degree during parturition.
ANTI‐INFLAMMATORY AND IRRITANT EFFECTS OF A FRACTION FROM NORMAL HUMAN PLASMA
Authors: ELLIOTT P.N.C. , FORD‐HUTCHINSON A.W. , SMITH M.J.H. 
Published: July 2012

By the use of carrageenan‐induced rat paw oedema assay the anti‐inflammatory activity of a fraction isolated from normal human plasma has been measured after its intravenous, intraperitoneal and oral administration. Its effects in the dextran‐induced rat paw oedema and the systemic dextran anaphylactoid reaction in the rat were also studied.
The fraction showed marked anti‐inflammatory activity in the carrageenan test after intravenous administration and a smaller but still significant activity when given intraperitoneally, but was inactive orally after the administration of a larger dose. It was active in the dextran‐induced paw oedema test but not against the anaphylactoid reaction.
A comparison between its anti‐inflammatory and irritant properties revealed no correlation when each parameter was determined in relation to dose. The fraction did not affect the blood pressure of the anaesthetized rat.
These findings are discussed in relation to the existence of a natural anti‐inflammatory substance or substances in human plasma.
MODIFICATION OF BRAIN ACETYLCHOLINE RELEASE BY MORPHINE AND ITS ANTAGONISTS IN NORMAL AND MORPHINE‐DEPENDENT RATS
Authors: JHAMANDAS K. , SUTAK M. 
Published: July 2012

The spontaneous release of acetylcholine (ACh) from the cerebral cortex of control and morphine‐dependent rats was investigated. The rate of resting output of ACh in morphine‐dependent animals was lower than that in the control animals.
Administration of naloxone and nalorphine to morphine‐dependent rats was followed by a significant rise in the release of cortical ACh. In control rats no such increase in the release of ACh occurred after similar injections of narcotic antagonists.
Injections of morphine produced a consistent decrease in the rate of spontaneous release of cortical ACh in the control rats, but similar injections in the dependent rats did not produce a decrease in the rate of cortical ACh release.
The relevance of these results with regard to development of the narcotic abstinence syndrome is discussed.
EFFECTS OF LITHIUM IONS ON ELECTRICAL ACTIVITY IN SYMPATHETIC GANGLIA OF THE BULLFROG
Authors: KOKETSU K. , YAMAMOTO K. 
Published: July 2012

The mode of action of lithium on electrical activity in the sympathetic ganglia of the bullfrog has been studied by recording extracellular and intracellular potential changes. Changes in nerve conduction and various types of synaptic transmission were studied when sodium ions in the external solution were totally replaced by equimolar concentrations of lithium ions and also when lithium ions were added to the external Ringer solution.
Nerve conduction and nicotinic transmission in sympathetic ganglia were completely blocked in sodium‐free sucrose solution, but were restored when the preparations were transferred to a sodium‐free lithium solution.
In the sodium‐free lithium solution, the slow excitatory postsynaptic potential (e.p.s.p.) and muscarinic acetylcholine‐depolarization were restored while the slow inhibitory postsynaptic potential (i.p.s.p.) and the muscarinic acetylcholine‐hyperpolarization were not restored. Furthermore, the early after‐discharges were accelerated and the inhibition of after‐discharges was eliminated. These results support the hypothetical concept that the slow i.p.s.p. is generated by an activation of the electrogenic sodium pump.
In the sodium‐free lithium solution, restoration of nerve conduction and synaptic transmission were transient phenomena; both conduction and transmission were gradually blocked when preparations were soaked in the solution for long periods. The blockade appeared to be due to membrane depolarization.
When lithium ions (20 mm) were added to the Ringer solution, nicotinic transmission was depressed. The slow e.p.s.p. was also depressed, but less so than the slow i.p.s.p. The early after‐discharge was, however, accelerated; presumably due to the marked depression of the slow i.p.s.p. in this solution.
Changes in synaptic transmission in Ringer solution containing lithium ions could be explained by membrane depolarization, a reduction of acetylcholine release and a depression of the electrogenic sodium pump.
All results obtained in the present experiments could be explained by supposing that lithium ions are able to substitute for sodium ions in passive ionic membrane transport dependent on electrochemical energy but not in active ionic membrane transport dependent on metabolic energy.
INHIBITION BY CROMOGLYCATE OF HISTAMINE RELEASE FROM RAT PERITONEAL MAST CELLS INDUCED BY MIXTURES OF DEXTRAN, PHOSPHATIDYL SERINE AND CALCIUM IONS
Authors: GARLAND L.G. , MONGAR J.L. 
Published: July 2012

Dextran releases histamine from rat peritoneal mast cells in the presence but not in the absence of phosphatidyl serine (PS). With PS (10 μg/ml) present the effect of dextran was concentration‐dependent in the range of 0.2–6 mg/ml.
PS releases little histamine on its own but mixed with dextran (6 mg/ml) produces a graded effect in the range of 0.3–10 μg/ml.
The combination of dextran and PS releases no histamine in a medium containing less than 0.1 mm calcium. As the calcium concentration is increased, release occurs and a maximum is reached at calcium 1 mm; at higher concentrations release falls off sharply.
Histamine release by the combination of dextran (6 mg/ml), PS (10 μg/ml) and calcium (1.8 mm) is inhibited by cromoglycate in the same range (1–30 μm) that inhibits anaphylactic histamine release from rat peritoneal cells.
Inhibition by cromoglycate occurred with all dextran concentrations tested (0.2–15 mg/ml) but high concentrations of PS (30 and 100 μg/ml) overcame the effect of cromoglycate (2 and 10 μm). Calcium concentrations above 1 mm augmented inhibition by cromoglycate 2 and 10 μm.
THE EFFECTS OF ACUTELY ADMINISTERED ANALGESICS ON THE TURNOVER OF NORADRENALINE AND DOPAMINE IN VARIOUS REGIONS OF THE RAT BRAIN
Authors: SUGRUE M.F. 
Published: July 2012

Noradrenaline and dopamine turnover rates were determined following blockade of synthesis by α‐methyl‐p‐tyrosine. Morphine, pentazocine and methadone had no effect on steady state levels or on turnover of noradrenaline in whole brain and in the hypothalamus. Although morphine was without action on medulla‐pons noradrenaline steady state levels, a drug‐induced increase in turnover rate was observed which was antagonized by pretreatment with naloxone (5 mg/kg). Pentazocine and methadone failed to alter either the steady state level of noradrenaline in the medulla‐pons or its turnover rate.
Morphine accelerated the decline in striatal α‐methyl‐m‐tyramine levels following subcutaneous injection of α‐methyl‐m‐tyrosine 18 h previously.
All three drugs increased the turnover of dopamine in whole brain and corpus striatum although the striatal effect was prevented by naloxone pretreatment. The minimum doses of morphine, pentazocine and methadone required to elicit a significant effect on striatal dopamine turnover were 10 mg/kg, 30 mg/kg and 10 mg/kg respectively.
The possibility of a dopaminergic involvement in the antinociceptive effect of analgesics is discussed.
PROSTAGLANDIN INACTIVATION IN GUINEA‐PIG LUNG AND ITS INHIBITION
Authors: CRUTCHLEY D.J. , PIPER PRISCILLA J. 
Published: July 2012

Several compounds were tested for their ability to inhibit prostaglandin metabolism in guinea‐pig lungs.
In isolated perfused lungs polyphoretin phosphate (PPP) inhibited prostaglandin metabolism being active at concentrations greater than 100 ng/ml and having an ID50 of 2.15 μg/ml against prostaglandin E2 metabolism and 1.55 μg/ml against prostaglandin F2α metabolism.
At these doses no antagonism of the actions of prostaglandins was seen.
Diphloretin phosphate (DPP) was more active on a weight for weight basis and inhibition of inactivation of prostaglandins was seen at concentrations greater than 10 ng/ml, the ID50 being 0.54 μg/ml against both prostaglandins E2 and F2α.
At concentrations greater than 5 μg/ml DPP antagonized the actions of prostaglandin F2∞.
The sulphydryl‐binders N‐ethyl maleimide (NEM) and sodium p‐chloromercuriphenyl sulphonate (PCMS) also inhibited prostaglandin inactivation by guinea‐pig isolated lungs.
All four compounds inhibited prostaglandin metabolism by a crude enzyme preparation from guinea‐pig lungs.
THE EFFECTS OF THREE β‐ADRENOCEPTOR BLOCKING DRUGS ON ISOLATED PREPARATIONS OF SKELETAL AND CARDIAC MUSCLE
Authors: HARRY J.D. , LINDEN R.J. , SNOW H.M. 
Published: July 2012

The effects of propranolol, oxprenolol and practolol on the isometric twitch responses to electrical stimulation of isolated diaphragm muscles from the rat and of isolated papillary muscles from the rabbit are described.Depression of the twitch responses of the diaphragm muscle was produced by propranolol (20 μg/ml), by oxprenolol (100 μg/ml) and by practolol (500 μg/ml).Depression of the twitch responses of the papillary muscles was produced by propranolol (20 μg/ml) by oxprenolol (100 μg/ml) and by practolol (200 μg/ml).No increase of twitch tension was produced by oxprenolol or practolol on either tissue.It is concluded that propranolol, oxprenolol and practolol produce negative inotropic actions on isolated cardiac muscle by a mechanism unrelated to blockade of β‐adrenoceptors and which occurs at doses which are well in excess of those doses required to produce β‐blockade.
A SENSITIVE METHOD FOR THE ASSAY OF OXYTOCIN IN THE CIRCULATING BLOOD
Authors: VANE J.R. , WILLIAMS K.I. 
Published: July 2012

The sensitivity of a wide range of isolated tissues to oxytocin was investigated. The longitudinal muscle strip of duck pulmonary vein proved the most suitable tissue for use with the superfusion technique, contracting to concentrations of oxytocin as low as 10 μu/ml.
The duck pulmonary vein superfused with Krebs solution was contracted by oxytocin, the vasopressins, adrenaline, noradrenaline, 5‐hydroxytryptamine, histamine and angiotensin II. Pre‐treatment of the preparation with phenoxybenzamine (1–2 μg/ml) abolished the contractions to catecholamines and reduced the effects of histamine and 5‐hydroxytryptamine without affecting the sensitivity to oxytocin.
The pulmonary vein contracted when superfused with blood from an anaesthetized dog. This contraction was accompanied by a non‐specific loss of responsiveness. When the pulmonary vein was superfused with Krebs solution that had been dialysed against blood the initial contraction was greatly reduced or abolished as was the loss in responsiveness.
Oxytocin was stable in circulating dog's blood but approximately 50% was bound to plasma proteins. Oxytocin was not destroyed in the pulmonary circulation or the hind limbs. In the doses used oxytocin had a half‐life of 60–90 s in the circulation of the dog under steady‐state conditions. Disappearance occurred chiefly in the visceral vascular beds.
SUPERSENSITIVITY TO ISOPRENALINE INDUCED IN RATS BY PROLONGED ISOLATION
Authors: SPEISER ZIPORA , WEINSTOCK MARTA 
Published: July 2012

The effect of isoprenaline on diastolic blood pressure and heart rate was determined in anaesthetized male rats which had been housed individually for 6–8 weeks after weaning, and compared with its effect in group‐housed litter‐mate controls.
Isoprenaline caused a significantly greater fall in diastolic pressure in isolated rats and a greater increase in heart rate.
Low doses of noradrenaline (5–10 ng) caused vasodepressor responses in isolated, but not in group‐housed rats.
The pressor response to noradrenaline, which was smaller in isolated rats, was increased to the level of group‐housed controls by (±)‐propranolol.
Prolonged isolation of rats may bring about an increase in sensitivity of β‐adrenoceptors to isoprenaline and noradrenaline.