bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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

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.
PROSTAGLANDINS E1 AND E2 PREVENT BRONCHOCONSTRICTION IN THE GUINEA‐PIG
Authors: HERXHEIMER H.
Published: July 2012

Prostaglandin E1 and E2 aerosols protected the guinea‐pig against bronchoconstriction caused by anaphylactic microshock, 1% histamine, 4% acetylcholine and 1% 5‐hydroxytryptamine aerosols.
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.
THE EFFECT OF SYMPATHOMIMETIC AMINES ON THE VENTRICULAR FIBRILLATION THRESHOLD IN THE RABBIT ISOLATED HEART
Authors: MURNAGHAN M.F.
Published: July 2012

The ventricular fibrillation threshold (VFT) was measured in the isolated heart of the rabbit perfused via the aorta with McEwen's solution at 37° C by applying a single 10 ms pulse of current during the vulnerable period of late systole. The arrhythmia induced was either fibrillation or a rapid tachycardia.

The catecholamines adrenaline, noradrenaline and isoprenaline, but not dopamine, when infused at rates which produced similar moderate effects on cardiac rate and force, significantly lowered the VFT; it was reduced slightly more by adrenaline than by the other two. Phenylephrine and methoxamine were ineffective. Only those sympathomimetic amines which lowered the VFT also shortened the vulnerable time, i.e. minimal time after the R‐wave of the ECG at which the pulse had to be applied to induce the arrhythmia.

The lowering effect of adrenaline on the VFT was not influenced by phentolamine but was blocked by propranolol and pindolol.

Chloroform potentiated the lowering effect of adrenaline, but not that of isoprenaline, on the VFT. Carbachol did not alter the effect of adrenaline on the VFT.

The results indicate that adrenaline, noradrenaline and isoprenaline lower the VFT by a direct action on the cardiac musculature and that this effect is mediated via β‐adrenoceptors.
SOME CENTRAL EFFECTS OF 5‐HYDROXYTRYPTAMINE IN YOUNG CHICKENS AT AND BELOW THERMONEUTRALITY
Authors: MARLEY E. , WHELAN JENNIFER E.
Published: July 2012

Three salts of 5‐hydroxytryptamine, the hydrogen maleinate, the oxalate and the creatinine sulphate were infused into the hypothalamus of 10‐18 day old chickens at ambient temperatures in and below the thermoneutral range. Body temperature was recorded and behaviour observed. Electrocortigrams were recorded in experiments in which 5‐hydroxytryptamine hydrogen maleinate was used. The effects of a monoamine oxidase inhibitor and methysergide on these responses were similarly studied.

At thermoneutrality (31° C) all 3 salts produced behavioural sleep. 5‐Hydroxytryptamine oxalate had inconsistent effects on body temperature. 5‐Hydroxytryptamine creatinine sulphate produced hypothermia at small doses and mild hyperthermia at higher doses. 5‐Hydroxytryptamine hydrogen maleinate produced hypothermia at all doses tested; the falls in temperature induced by this salt were intensified in magnitude and duration by monoamine oxidase inhibition unlike the responses to the other 2 salts.

At temperatures below thermoneutrality (16° C) all 3 salts produced behavioural sleep and electrocortical sleep was recorded with 5‐hydroxytryptamine hydrogen maleinate. All 3 salts produced hypothermia, which was intensified in magnitude and duration by monoamine oxidase inhibition.

The hypothermia produced by 5‐hydroxytryptamine hydrogen maleinate was prevented by equimolar doses of methysergide.

The position of the cannula in the hypothalamus was found to be crucial.

The results contrast with those found in the adult fowl. No conclusion is drawn as to the relationships of the actions of these salts when infused compared with the effects of endogenous 5‐hydroxytryptamine release.
INFLUENCE OF HISTAIMINE H1 AND H2‐RECEPTOR BLOCKERS ON SYMPATHETIC VASODILATOR AND VASOCONSTRICTOR RESPONSES IN CANINE PAW
Authors: KRAFT E. , ZIMMERMAN B.G.
Published: July 2012

Vasodilator responses to histamine, bradykinin and sympathetic nerve stimulation were elicited in the perfused paw of dogs treated with bretylium (15‐20 mg/kg) and atropine. The H2‐receptor blocking agent, burimamide, when administered in the dose of 5 mg/kg intravenously and 4 mg intra‐arterially did not depress significantly these vasodilator responses. The subsequent administration of tripelennamine in the dose of 2.5‐5 mg/kg intravenously and 4 mg intra‐arterially produced a significant blockade of the response to histamine and reduced the sustained vasodilator response to nerve stimulation.

In guanethidine‐treated dogs, tripelennamine administered in the same dose following burimamide produced a blockade of the respone to histamine comparable to that in the bretylium experiments, but decreased only the sustained vasodilator response to stimulation at 1 Hz. When the order of administration of the antihistamines was reversed in another group of guanethidine‐treated dogs, tripelennamine had only a slight blocking effect on the response to histamine and did not affect the responses to nerve stimulation. Burimamide exerted a significant blocking effect on the response to histamine, but not to nerve stimulation. Another H2‐receptor blocking agent, metiamide, when given after tripelennamine, also had a marked blocking effect on the response to histamine and almost abolished the vasodilator response to 4‐methylhistamine, an H2‐agonist. Nevertheless, even in the presence of this profound histamine blockade, the sustained vasodilator response to nerve stimulation remained unchanged.

In another group of experiments vasoconstrictor responses to exogenous noradrenaline and sympathetic stimulation were initially depressed by burimamide and later returned to control values. Tripelennamine increased these responses by its uptake blocking action.

It is concluded that the sustained vasodilator response is not antagonized by a specific antihistaminic action. The decrease in the sustained vasodilator response produced by antihistamines is probably attributable to potentiation of a residual adrenergic vasoconstrictor effect not completely blocked by bretylium.
A FURTHER INVESTIGATION INTO THE ENERGY DEPENDENCE OF ANGIOTENSIN II‐INDUCED CONTRACTIONS OF ISOLATED SMOOTH MUSCLE PREPARATIONS
Authors: CROCKER ANN D. , WILSON K.A.
Published: July 2012

The energy dependence of angiotensin and acetylcholine‐induced contractions of rat descending colon and uterus was investigated.

Differences were observed in the effect of anaerobic substrate depletion upon responses of colon and oestrous and dioestrous uterus. These were attributed to differences in the energy metabolism of the tissues and were correlated with differences in tissue levels of glycogen.

The preferential reduction of angiotensin responses of dioestrous uterus and descending colon when exposed to 2,4‐dinitrophenol, was evidence for an energy dependent stage in the angiotensin response distinct from the contraction process itself.

The absence of a preferential reduction of the angiotensin response of oestrous uterus when exposed to 2,4‐dinitrophenol appeared to be related to the ability of this tissue to generate ATP by anaerobic glycolysis.

It was concluded that the energy for the angiotensin response may be derived either anaerobically or aerobically, depending upon the tissue.
EVIDENCE THAT ADRENERGIC NERVES ARE RESPONSIBLE FOR THE ACTIVE UPTAKE OF NORADRENALINE IN THE GUINEA‐PIG ISOLATED TRACHEA
Authors: FOSTER R.W. , O'DONNELL STELLA R.
Published: July 2012

6‐Hydroxydopamine (50 mg/kg, i.p.) was given to guinea‐pigs to destroy the adrenergic nerve terminals in the trachea.

The destruction was demonstrated by fluorescence histochemistry, which showed a marked loss of beaded fluorescent terminal fibres and by electrical transmural stimulation of the isolated atropinized trachea, which showed a marked reduction of dilator responses.

Such tracheae showed greatly reduced uptake‐with‐retention of (—)‐[3 H]‐noradrenaline in incubation experiments and the efflux curve of radioactive material showed a selective but incomplete reduction in the volume of the slowly exchanging compartment.

It is concluded that much, but perhaps not all, of the uptake‐with‐retention occurs into adrenergic nerves.
ACTIVATION OF HISTIDINE DECARBOXYLASE BY H2‐RECEPTOR BLOCKADE: MECHANISM OF ACTION
Authors: HÅKANSON R. , HEDENBRO J. , LIEDBERG G. , REHFELD J.F. , STADIL F.
Published: July 2012

Treatment with histamine H2‐receptor antagonists, which inhibit basal acid secretion, was found to activate rat stomach histidine decarboxylase. At the same time the serum gastrin concentration was greatly increased.

In antrectomized rats neither the enzyme activity nor the serum gastrin concentration was affected by the treatment.

In analogy with previous observations on other inhibitors of acid secretion we suggest that the H2‐receptor antagonists stimulate gastrin release through their effect on acid secretion and that the raised serum gastrin level is responsible for the enzyme activation.
AN ANALYSIS OF THE PHENOMENON OF ACUTE TOLERANCE TO MORPHINE IN THE GUINEA‐PIG ISOLATED ILEUM
Authors: KOSTERLITZ H.W. , WATERFIELD ANGELA A.
Published: July 2012

The observations which Paton (1957) interpreted as ‘acute tolerance’ and ‘dependence’ have been confirmed for coaxially stimulated segments of guinea‐pig ileum and extended to the contractions evoked by field stimulation in the myenteric plexus‐longitudinal muscle preparation. Evidence is adduced that the morphine receptors of the myenteric plexus are not involved in the two phenomena.

The contraction of the longitudinal muscle depressed by low concentrations of morphine, or levorphanol, can be restored to control level not only by high concentrations of morphine but also by levorphanol and equally well by its (+)‐isomer, dextrorphan, which does not fulfil the stereospecific requirements of the morphine receptor. Acetylcholine output was not increased.

When, after restoration of the twitch by high concentrations of morphine, the drug is washed out, contractions become depressed. This effect cannot be due to ‘dependence’ because either morphine or its antagonist, naloxone, restore the twitch again.

In the concentrations used, morphine, levorphanol and dextrorphan inhibit the Cholinesterase of homogenates of the myenteric plexus‐longitudinal muscle preparation by 10‐15%, Since a concentration of physostigmine which causes a similar inhibition also restores the twitch, it is concluded that the described phenomena are best explained by the anticholinesterase effects of the drugs.
INDOMETHACIN, KETOPROFEN AND CORPUS LUTEUM REGRESSION IN THE GUINEA‐PIG
Authors: DONOVAN B.T.
Published: July 2012

The accelerated regression of the corpora lutea normally produced by glass beads inserted unilaterally into the uterus of the guinea‐pig early in the oestrous cycle was prevented when the beads were filled with indomethacin or ketoprofen.

Luteal regression was enhanced by the placement of beads in both horns of the uterus. When empty beads were placed in one horn of the uterus and drug‐filled beads in the other, indomethacin blocked regression in both ovaries whereas ketoprofen was ineffective.

Indomethacin probably blocks luteal regression by inhibition of prostaglandin synthesis in the uterus.
SYNTHESIS OF KALLIKREINS BY RAT KIDNEY SLICES
Authors: NUSTAD K. , VAAJE KIRSTEN , PIERCE J.V.
Published: July 2012

Four radioactive kallikreins were isolated from rat kidney slices incubated with [3 H]‐L‐leucine.

The kallikreins were purified by procedures previously used for the isolation of rat urinary kallikreins (Nustad & Pierce, 1974), and by affinity chromatography on a column of insolubilized anti‐rat urinary kallikrein.

The kidney kallikreins resembled the urinary kallikreins in their relative amounts, isoelectric points and electrophoretic mobilities on polyacrylamide disc gels.

The data indicate that the kidney synthesizes four kallikreins which are released into urine. The kallikreins are not changed by passage through the lower urinary tract.
THE DISTRIBUTION OF LITHIUM, SODIUM AND MAGNESIUM IN RAT BRAIN AND PLASMA AFTER VARIOUS PERIODS OF ADMINISTRATION OF LITHIUM IN THE DIET
Authors: BOND P.A. , BROOKS B.A. , JUDD A.
Published: July 2012

The tissue solubilizer Soluene‐100 provides an efficient and easy means of preparing small amounts of rat tissue for cation analysis.

Administration of lithium ions to rats for two days to 42 days by the addition of lithium chloride to the diet at a concentration of 30 mmol/kg dry weight results in (a) the uniform distribution of lithium throughout the brain at a concentration comparable to that found in plasma; (b) decrease in the brain sodium concentration; (c) a decrease in brain magnesium concentration and an increase in plasma magnesium concentration; (d) no change in brain water content.

The inclusion of LiCl in the diet at a concentration of 30 mmol/kg dry food gives consistent and predictable plasma and brain levels of lithium in the rat without the occurrence of serious side effects over periods of up to 42 days.
DISCRIMINATION OF MONOAMINE UPTAKE BY MEMBRANES OF ADRENAL CHROMAFFIN GRANULES
Authors: DA PRADA M. , OBRIST R. , PLETSCHER A.
Published: July 2012

The accumulation of various radioactive monoamines by isolated membranes of bovine adrenal chromaffin granules was measured by equilibrium dialysis.

Adenosine‐5′‐triphosphate (ATP) in the presence of Mg++ stimulated the uptake of all the amines tested, but the accumulation of dopamine, (‐)‐noradrenaline (NA), 5‐hydroxytryptamine (5‐HT), (±)‐adrenaline and (±)‐octopamine was greater than that of tyramine, (±)‐metaraminol, tryptamine, β‐phenylethy lamine and histamine.

At the higher concentration levels of the amines in the medium the ATP‐dependent accumulation of dopamine, NA, adrenaline and 5‐HT in the membranes reached a saturation level, whereas in the absence of the nucleotide no saturation level was attained.

Octopamine and 5‐HT competitively inhibited the ATP‐dependent uptake of NA.

Decrease in the incubation temperature or the presence of N‐ethylmaleimide greatly reduced the ATP‐stimulated amine accumulation. Ouabain had no effect on uptake.

Reserpine virtually abolished the ATP‐dependent uptake of dopamine, NA and 5‐HT, caused a partial inhibition of the metaraminol, octopamine and tyramine accumulation, but did not interfere with the uptake of tryptamine.

The content of endogenous catecholamines of the membranes was changed very little by incubation of NA and 5‐HT in the presence of ATP. However, the membranes lost over 80% of their endogenous amines if incubated for 30 min without ATP.

The ATP content of the medium progressively decreased during the incubation of granular membranes.

It is concluded that the membrane of adrenal chromaffin granules discriminates between the various monoamines with regard to the magnitude of their uptake and that two mechanisms of ATP‐stimulated uptake, one responsive and the other resistant to reserpine, exist at the level of this membrane. The ATP‐stimulated transport at the granular membrane level may be an important factor in determining the intraneuronal storage of a physiological or false neurotransmitter.
ROLE OF EXTRANEURONAL MECHANISMS IN THE TERMINATION OF CONTRACTILE RESPONSES TO AMINES IN VASCULAR TISSUE
Authors: KALSNER S.
Published: July 2012

The role of the uptake and release of agonist from extraneuronal sites in the termination of responses of rabbit aortic strips to amines was studied.

Strips were contracted with adrenaline or noradrenaline and after a response plateau was reached, the muscle chambers were washed free of agonist and the relaxation in Krebs solution recorded. After inhibition of catechol‐O‐methyl‐transferase, monoamine oxidase and neuronal uptake the relaxation rate was greatly prolonged. Evidence is provided that this very slow relaxation resulted from the accumulation of intact amine at extraneuronal sites during exposure to the agonist and its subsequent release past receptors due to a reversal of the concentration gradient after washout.

Pretreatment with the haloalkylamine, GD‐131 (N‐cyclohexylmethyl‐N‐ethyl‐β‐chloroethylamine), an inhibitor of extraneuronal uptake, returned the slow relaxation rate after enzyme inhibition towards that of control strips. By blocking the extraneuronal transport of amines their accumulation at intracellular loci after enzyme inhibition was prevented.

The effects of GD‐131 and 17β‐oestradiol on the relaxation rate of untreated strips contracted by adrenaline and noradrenaline confirmed that extraneuronal uptake to sites of enzymatic activity is the major mechanism terminating their action.

Inactivation of extraneuronal transport sites by GD‐131 was prevented by protecting them with 17β‐oestradiol or normetanephrine during exposure to the haloalkylamine, pointing to a common site of action of these agents on a specific carrier system for amines.

Evidence is presented that the relaxation from contractions induced by histamine and 5‐hydroxytryptamine also involves extraneuronal accumulation and release, probably by an uptake process which is identical to the one for catecholamines.
STUDIES ON THE HYPOTENSIVE ACTION OF α‐METHYLDOPAMINE
Authors: FINCH L. , HERSOM A. , HICKS P.
Published: July 2012

Intraventricular α‐methyldopamine (50–200 μg) produced a dose‐related fall in blood pressure in conscious spontaneously hypertensive rats. Pretreatment with intraventricular 6‐hydroxydopamine prevented this hypotensive effect of α‐methyldopamine.

The hypotensive effect of α‐methyldopamine was prevented by intraventricular injection of phentolamine or desmethylimipramine, but not by intraperitoneal injection of haloperidol.

Pretreatment with U‐14,624, a selective central dopamine‐β‐hydroxylase inhibitor, prevented the hypotensive effect of α‐methyldopamine.

α‐Methyldopamine was considerably less potent than noradrenaline as a pressor agent in the pithed rat, but noradrenaline and α‐methylnoradrenaline were found to be equipotent.

α‐Methyldopamine (1–5 mg i.c.v.) reduced pressor responses elicited by electrical stimulation of the mid brain reticular formation in cats anaesthetized with chloralose.

It is concluded that the hypotensive action of α‐methyldopamine in conscious animals involves intact central α‐adrenergic neurones and a central adrenergic uptake mechanism for the formation of α‐methylnoradrenaline.
HYPOTHERMIC EFFECT OF SODIUM ACETYLSALICYLATE ON AFEBRILE MONKEYS
Authors: CHAI C.Y. , LIN M.T.
Published: July 2012

Afebrile monkeys (Macaca cyclopis) receiving systemic (100–300 mg/kg, i.p.) or central (5–20 mg into the 3rd cerebral ventricle) administration of sodium acetylsalicylate showed a dose‐dependent reduction in rectal temperature in a thermoneutral environment (25° C).

Administration of sodium acetylsalicylate (10 mg) into the 3rd cerebral ventricle produced a hypothermia with a temperature decrement of 1.0° C, while an intraperitoneal injection of 300 mg/kg was required for a temperature decrement of 0.9° C. The ratio between the total doses given by the two routes was 1 to 120.

Following the administration of sodium acetylsalicylate, a decline in rectal temperature was accompanied by a tail cutaneous vasodilatation.

The data suggest that sodium acetylsalicylate can lower the normal body temperature by activating heat loss or decreasing the normal (tonic) inhibition of the heat loss mechanism via the central nervous system.
RAT SUBMANDIBULAR GLAND KALLIKREINS: PURIFICATION AND CELLULAR LOCALIZATION
Authors: BRANDTZAEG P. , GAUTVIK K.M. , NUSTAD K. , PIERCE J.V.
Published: July 2012

Four submandibular gland kallikreins (E.C. 3.4.21.8) were isolated by chromatography on DEAE‐Sephadex A‐50 and hydroxyapatite, followed by gel filtration and electrofocusing. The pI values were 3.87, 3.96, 4.07 and 4.16, and a common molecular weight of 34,000 was found.

The kallikreins were localized by direct immunofluorescence with an antibody to rat urinary kallikrein, to the granular tubules, striated duct cells and some main duct cells in the submandibular gland, and to striated duct cells in the sublingual gland. Kallikrein was not found in acini and stroma.

Several non‐kallikrein esterases present in the submandibular gland reacted with the antibody to rat urinary kallikrein. The antibody was made monospecific for kallikrein by absorption with the crossreacting esterases.

We suggest that kallikrein is produced in striated duct cells. Granular tubules, which are differentiated from striated duct cells, have preserved the ability to produce kallikrein. These cells also store large quantities of kallikrein.
THE EVALUATION OF THE NOVEL PRESSOR ACTIVITY OF γ‐PIPERIDINOBUTYRAMIDE (WY 20051, DF480)
Authors: ALPS B.J. , DEVOY P.W. , WATERFALL J.F.
Published: July 2012

γ‐Piperidinobutyramide (Wy 20051, DF480) injected intravenously evoked pressor responses in the anaesthetized ganglion blocked rat preparation over the dose range 2.4 × 10−6‐3.0 × 10−4 mol/kg.

High doses (>3.8 × 10−5 mol/kg) or even repeated submaximal doses (1.9 × 10−5 mol/kg) of Wy 20051 caused tachyphylaxis of this pressor response.

The noradrenaline pressor‐response curve was shifted significantly to the right of the control curve following a dose of Wy 20051 (1.5 × 10−4 mol/kg cumulative).

The dose‐response curve for the pressor action of Wy 20051 was potentiated in reserpine‐treated anaesthetized rats. In contrast, tyramine‐induced pressor responses were abolished.

Wy 20051 contracted the guinea‐pig isolated aortic spiral preparation (3.8 × 10−5‐6.0 × 10−4 mol) and evoked constrictor responses in the perfused mesenteric vasculature preparation of the rat (5.9 × 10−7‐1.2 × 10−5 mol). At higher doses the responses were reduced.

Wy 20051‐induced constrictor responses of the perfused mesentery were unaffected by blockade of α‐adrenoceptors or by tachyphylaxis of 5‐hydroxytryptamine receptors.

The time for abolition of Wy 20051‐induced constrictor responses of the mesentery in a calcium‐free medium was not significantly different from that required for noradrenaline, but was significantly greater than that for KCl (P < 0.001).

Wy 20051 and noradrenaline, but not KCl, evoked constrictor responses in the depolarized rat mesenteric vasculature.

The results indicate that Wy 20051 evokes pressor responses which have some of the characteristics of those of noradrenaline. However, the responses are not elicited by an α‐adrenoceptor mechanism.
HYPOTHALAMO‐PITUITARY ADRENOCORTICAL FUNCTION IN THE RAT AFTER TREATMENT WITH BETAMETHASONE
Authors: BUCKINGHAM JULIA C. , HODGES J.R.
Published: July 2012

Hypothalamo‐pituitary‐adrenocortical (HPA) activity was suppressed in rats treated with betamethasone.

Recovery of normal HPA function occurred after corticosteroid withdrawal.

Although corticotrophin release was rapidly restored to its basal rate there was a delay in the return of the normal adrenocorticotrophic response to stress and normal adrenocortical function was evident only after the plasma adrenocorticotrophic hormone had reached ‘supra‐normal’ levels.

The physiological significance and possible clinical relevance of the results are discussed.
ON THE MECHANISM OF ACTION OF CLOZAPINE ON THE ADRENERGIC NEURONE
Authors: DORRIS R.L. , SHORE P.A.
Published: July 2012

The antipsychotic drug, clozapine, lowered noradrenaline and metaraminol (MA) concentrations in the rat heart. This action was blocked by the presence of a ganglionic blocking drug.

Other α‐adrenoceptor blocking drugs (phenoxybenzamine, phentolamine) did not significantly lower heart amine concentrations. An inhibitor of neuronal amine uptake (desipramine) caused only a slight lowering. The combination of phentolamine and desipramine showed considerable activity, and this action was blocked by ganglionic blockade.

Clozapine had little or no action in blocking amine uptake, yet greatly potentiated amine release caused by the phentolamine‐desipramine combination.

Other antipsychotic drugs (haloperidol, chlorpromazine, thioridazine) or other agents (propranolol, atropine) did not share this action of clozapine.

Ganglionic blockade markedly delayed amine release induced by reserpine administration.

It is suggested that clozapine may have an incomplete reserpine‐like effect specifically on the adrenergic neurone, facilitating impulse‐induced amine release.
THE EFFECTS OF PROSTAGLANDINS E1, E2 AND F2α ON THE CUTANEOUS VASCULATURE OF THE RAT
Authors: CHAHL LORIS A. , LADD R.J.
Published: July 2012

The responses of the rat cutaneous vasculature to prostaglandins E1, E2 and F2α have been investigated by a photomicrographic technique.

Prostaglandin E1 produced transient arterial constriction which was blocked by local pretreatment of preparations with compound 48/80 or methysergide. It was concluded that prostaglandin E1 produced vasoconstriction by release of 5‐hydroxytryptamine (5‐HT) from mast cells. The magnitude of the vasoconstrictor response appeared to be subject to seasonal variation.

Prostaglandin F2α produced arterial constriction of longer duration which was not blocked by compound 48/80, methysergide or phenoxybenzamine.

Preparations pretreated with prostaglandin F2α were found to be more sensitive to the venous constrictor effect, and less sensitive to the arterial constrictor effect, of noradrenaline.

Prostaglandin E2 produced arterial constriction which was usually partially blocked by compound 48/80 and methysergide and it was concluded that a major component of the vasoconstrictor response to prostaglandin E2 was of the E1 type but some component was of the F2α type.
EFFECTS OF AMINO ACIDS AND CONVULSANTS ON SPONTANEOUS ACTION POTENTIALS IN CEREBELLAR CORTEX SLICES
Authors: OKAMOTO K. , QUASTEL J.H.
Published: July 2012

Picrotoxin selectively and reversibly suppressed the inhibitory action of γ‐aminobutyric acid (GABA), but not that of glycine, taurine or β‐alanine, on the frequency of spontaneous spike discharges in guinea‐pig cerebellar slices. Strychnine reversibly suppressed the inhibitory action of glycine, taurine or β‐alanine but had no effect on that of GABA.

GABA, glycine, taurine and β‐alanine showed an early excitatory effect that was unaffected by picrotoxin or strychnine.

Studies of the dose‐response relations indicated a competition between the amino acid and the convulsant at a common receptor site.

Kinetic analyses of the dose‐response relations for the amino acids in the presence or absence of picrotoxin or strychnine indicated that the number of molecules of amino acid combining with the receptor site in order to produce a response (inhibition or excitation) was 3 for GABA, 2 for glycine, 3 for taurine and 4 for β‐alanine. There appeared to be no evidence that the response was due to the cooperativity between the amino acid receptor complexes. The number of molecules of convulsant that combined with the receptor site was 1 for either strychnine or Picrotoxin.

Mixtures of glycine with taurine or β‐alanine, in contrast to those with GABA, appeared not to give additive inhibitory effects.