bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase separation in solutions of noradrenaline and adenosine triphosphate: influence of bivalent cations and drugs
Authors: BERNEIS K. H. , PLETSCHER A. , DA PRADA M. 
Published: July 2012

Summary
From aqueous solutions of biogenic amines, such as noradrenaline plus adenosine triphosphate (ATP), a second liquid phase spontaneously separates in the presence of small amounts of bivalent cations such as calcium. This separation is reversible and temperature‐dependent; the concentration of amine and ATP in the bottom phase is several times higher than in the supernatant.
Analytical ultracentrifugation provides evidence that the second phase consists of high molecular weight aggregates of the amine and ATP.
The separated second phase of the noradrenaline‐ATP system dissolves isothermally on addition of tyramine and amphetamine which in vivo are known to liberate biogenic monoamines and which have a low tendency to aggregate with ATP. The apparent molecular weights of noradrenaline‐ATP aggregates are decreased by tyramine and amphetamine. Dopamine does not diminish the second phase and it can also form aggregates of high molecular weight with ATP.
Bivalent cations in high concentrations diminish or abolish the separation of a second phase.
Small amounts of reserpine affect phase separation.
It is concluded that the physico‐chemical properties of aggregates of biogenic amines with ATP may be of importance for understanding the storage and release of the amines in vivo.
Interactions of inhibitors of noradrenaline uptake and angiotensin on the sympathetic nerves of the isolated rabbit heart
Authors: SCHÜMANN H. J. , STARKE K. , WERNER U. 
Published: July 2012

Summary
The interaction of angiotensin and several inhibitors of the uptake of noradrenaline across the neuronal membrane (cocaine, desipramine, protriptyline, and pronethalol) on the output of noradrenaline produced by sympathetic nerve stimulation has been studied in the isolated perfused rabbit heart.
Most of these drugs increased noradrenaline outflow—angiotensin, for example, by 175%. Cocaine (10−4m) did not change the amine overflow, probably because this very high concentration inhibited not only the re‐uptake but also the liberation of noradrenaline.
Desipramine, protriptyline, and pronethalol, although infused in concentrations which enhanced the noradrenaline output, were not able to impair the angiotensin‐induced increase of transmitter overflow. In the presence of cocaine (10−4m) the increase elicited by angiotensin was slightly reduced, though lower concentrations of cocaine, as previously described, do not interfere with the effect of angiotensin.
In contrast to the interaction between uptake inhibitors and angiotensin, the augmented output of noradrenaline caused by an uptake inhibitor could not be increased further by infusion of a second uptake inhibitor.
It is concluded that the increase of the outflow of noradrenaline during sympathetic nerve stimulation by small doses of angiotensin is not caused by an inhibition of re‐uptake. On the contrary, the transmitter liberation seems to be facilitated. This is a novel principle of drug action on the sympathetic nerve terminals.
The distribution of antibacterial agents between plasma and lymph in the dog
Authors: ACRED P. , BROWN D. M. , CLARK B. F. , MIZEN LINDA 
Published: July 2012

Summary
Plasma, peripheral and thoracic lymph concentrations of penicillin V, phenethicillin, carbenicillin, ampicillin, cloxacillin, penicillin G, chloramphenicol and sulphadiazine were determined at various time intervals up to 6 h following intramuscular administration of 50 mg/kg to dogs.
Peak plasma concentrations of the penicillins occurred within half an hour after administration with the peak lymphatic concentrations occurring 1.5 to 3 h afterwards. For the remaining period of the test the concentration in the lymph exceeded the corresponding concentration in the plasma. Sulphadiazine gave concentrations in thoracic lymph equal to the plasma concentration, but the peripheral lymph concentrations were lower while the concentrations of chloramphenicol in both peripheral and thoracic lymph were always lower than the plasma concentrations.
After the peak concentrations were reached, the concentration curves for penicillins in lymph followed the same pattern as found in plasma, the penicillin concentrations declining exponentially. Sulphadiazine produced more persistent levels both in lymph and in plasma while the concentrations of chloramphenicol were still rising 6 h after administration.
The free concentrations of penicillin in lymph were equal to the free concentrations in plasma, whereas the concentrations of free sulphadiazine and chloramphenicol in lymph were less than those in the plasma.
Protection against burn, tourniquet and endotoxin shock by histamine, 5‐hydroxytryptamine and 5‐hydroxytryptamine derivatives
Authors: MARKLEY K. , SMALLMAN ELIZABETH , THORNTON S. W. 
Published: July 2012

Summary
5‐Hydroxytryptamine (5‐HT), tryptamine, 5‐methyltryptamine, 5‐methoxytryptamine, N‐methyltryptamine, 5‐hydroxy‐N,N‐dimethyltryptamine, and histamine markedly protect mice subjected to burn, tourniquet and endotoxin shock. All of these compounds protect when given 30 min before the production of shock, but not when administered afterwards.
The above compounds, as well as purines and purine derivatives have a similar chemical structure. Protection requires the compounds to contain a 5‐membered ring with one unsubstituted N atom and a side chain with a basic N atom three atoms from the ring.
All other biological amines tested without this chemical structure did not protect.
Since the simplest compound containing all the prerequisites for protection is histamine, this compound may play the key role in protection, for both 5‐HT and purines release histamine from tissues.
Protective doses of 5‐HT and histamine prevent swelling of the injured area after tourniquet trauma and produce an increased bleeding volume and lower haematocrit value after burning. These actions of the drugs on the circulation may account for the increased survival after thermal trauma.
Uptake of nicotine and extracellular space markers by isolated rat ganglia in relation to receptor activation
Authors: BROWN D. A. , HALLIWELL J. V. , SCHOLFIELD C. N. 
Published: July 2012

Summary
Uptake of 3H‐nicotine by isolated rat superior cervical sympathetic (SCG) and nodose (NG) ganglia was measured in vitro. Depolarization of the ganglia by nicotine was measured electrically.
Nicotine depolarized the SCG but not the NG. The mean ED50 for depolarization was 5·3 × 10−6m.
Both ganglia accumulated nicotine when incubated in 3·1 × 10−5m 3H‐nicotine: after 30 min incubation the ratios of tissue to medium concentrations were (mean ± s.e. of mean): SCG, 3·49 ± 0·13; NG, 2·50 ± 0·09.
Total water contents, estimated by drying to constant weight, were: SCG, 83·8 ± 0·12%; NG, 80·1 ± 0·21%. Extracellular spaces, measured as 3H‐mannitol space, were: SCG, 38·8 ± 1·3; NG, 40·3 ± 0·8% wet weight. These values were not significantly altered by nicotine.
Correction for tissue fluid spaces indicated that the ratio of the mean intracellular fluid concentration to the extracellular fluid concentration for 3H‐nicotine at 3·1 × 10−5m were: SCG, 7·4; NG, 5·6. The ratios were not altered in any consistent manner on varying the nicotine concentration between 3·1 × 10−7 and 1·6 × 10−4m.
When the nicotine concentration was sufficiently great (6·2 × 10−6m or more) to evoke large SCG depolarizations, hexamethonium (2·5 × 10−3m) reduced 3H‐nicotine uptake by the SCG by up to 19% without affecting uptake by the NG, and thereby reduced the uptake difference between the two ganglia. With nicotine concentrations <6·2 × 10−6m, hexamethonium did not modify uptake by either ganglion.
It was concluded that nicotine may be concentrated within neurones, and that such intracellular accumulation may be augmented during depolarization induced by nicotine.
Inotropic actions of lignocaine and phenytoin
Authors: KENNEDY BARBARA L. , NOOKHWUN CHONGKOL , SADAVONGVIVAD CHIRAVAT , TANCHAJJA S. 
Published: July 2012

Summary
The inotropic effects of two antiarrhythmic drugs, lignocaine and phenytoin, were studied in electrically driven isolated rabbit atrial preparations. The time‐effect relationship of each drug was investigated with different concentrations and frequencies of stimulation.
The effects of time of exposure, drug concentration and heart rate on the development of beat alterations (cessation of beat, skipped beat, alternating variation of force of contraction and extrasystole) were also studied.
When the chronotropic effects of both drugs were prevented, the inotropic effects were positive or negative depending on the concentration of drug, time of exposure and frequency of stimulation.
At concentrations higher than those obtained in the blood of man on maintenance doses, alteration of the beat occurred but was consistent with the peak blood concentrations immediately after the injection of standard clinical doses. The time of onset of beat alteration shortened when either drug concentration or frequency of stimulation was increased.
The beat alteration produced by antiarrhythmic drugs can account for various adverse effects associated with their clinical use. These effects include transient ventricular tachycardia and extrasystole during and shortly after injection of drug, ventricular tachycardia, ventricular fibrillation and cardiac arrest due either to excessive dose or to persistent tachyarrhythmia if the dose is not excessive.
Evidence for the presence of α‐adrenoceptors in the central thermoregulatory mechanism of rabbits
Authors: DHAWAN B. N. , DUA P. R. 
Published: July 2012

Summary
The effects of intracerebroventricular administration of some α‐ and β‐adrenoceptor stimulants and antagonists on the body temperature of rabbits were investigated.
Noradrenaline produced a dose dependent rise in body temperature. Other catecholamines were less active.
The noradrenaline response was blocked by α‐adrenoceptor blocking agents while β‐adrenoceptor antagonists had no effect.
α‐Methyl‐noradrenaline and metaraminol had some hyperthermic effect, but significantly reduced the response of noradrenaline.
The possible presence of α‐adrenoceptors in the central thermoregulatory mechanisms is suggested.
Effect of receptor blocking drugs on the depletion of brain glycogen by amphetamine
Authors: HUTCHINS D. A. , ROGERS K. J. 
Published: July 2012

Summary
Amphetamine sulphate (5 mg/kg), administered intraperitoneally, reduces the concentration of glycogen in the mouse brain by 25–30% after 30 minutes.
The effect of several receptor blocking drugs on the amphetamine‐induced cerebral glycogenolysis was studied.
dl‐Propranolol (0·25 mg/kg) and pronethalol (10 mg/kg) antagonized the depletion of brain glycogen by amphetamine.
Phentolamine, methysergide, atropine and mepyramine failed to antagonize the amphetamine‐induced glycogenolysis.
d‐Propranolol, chlorpromazine and phenoxybenzamine antagonized the glycogenolytic effect of amphetamine only when administered in sedative doses.
It is concluded that amphetamine‐induced glycogenolysis in the mouse brain may be mediated through a β‐adrenoceptor.
1‐Hydroxy‐3‐amino‐pyrrolidone‐2 (HA‐966): a new GABA‐like compound, with potential use in extrapyramidal diseases
Authors: BONTA I. L. , DE VOS C. J. , GRIJSEN H. , HILLEN F. C. , NOACH E. L. , SIM A. W. 
Published: July 2012

Summary
The drug HA‐966 (1‐hydroxy‐3‐amino‐pyrrolidone‐2), which chemically resembles the cyclic form of GABA, has been studied for neuro‐pharmacological properties and for effects on the catecholamine content of the corpus striatum.
The acute effects on spontaneous behaviour of rodents included flaccid catalepsy and reversible tranquillization in doses which were 5% or less of the lethal dose. Long lasting depression of the CNS, followed by complete recovery, was produced in the cat and the dog. In the monkey HA‐966 caused periodical sleeping episodes.
The exploratory behaviour and the amphetamine‐induced motor activity in mice were blocked by HA‐966. The toxicity of amphetamine in aggregated mice was only moderately reduced, suggesting that HA‐966 differs from neuroleptics.
Tremors induced by chemical agents (nicotine, zinc and tremorine) were markedly inhibited by HA‐966. The muscarinic effects of tremorine were not reduced by HA‐966, indicating a selective central antitremor effect.
HA‐966 elevated the threshold to strychnine convulsions and abolished the ipsilateral flexor reflex, while not having motor endplate blocking properties. It is suggested that HA‐966 depresses central internuncial neurones.
In rats and rabbits HA‐966 produced synchronous EEG and inhibited the sensory arousal in doses not causing sedation. In the monkey the drug caused a periodical dissociation between ‘sleep‐EEG’ and behaviour.
In rat brain, HA‐966 selectively elevated the dopamine content in the corpus striatum, while no changes in noradrenaline and 5‐hydroxytryptamine contents could be demonstrated. The effect was still present when dopa synthesis was inhibited with α‐methyl‐p‐tyrosine.
Several effects of intravenously administered HA‐966 became manifest after an appreciable delay and in hepatectomized mice the effects were much reduced. It is postulated that HA‐966 is converted to a pharmacologically active metabolite.
The results are discussed in the light of current views on drug therapy in extrapyramidal conditions and a GABA‐related hypothesis as to the mode of action of HA‐966 is presented.
Effect of phenmetrazine, aminorex and (±) p‐chloramphetamine on the motor activity and turnover rate of brain catecholamines
Authors: COSTA E. , NAIMZADA K. M. , REVUELTA A. 
Published: July 2012

Summary
The minimal doses (μmol/kg i.v.) of phenmetrazine, (±)‐p‐chloramphetamine, and aminorex which increase motor activity are 5·6, 3·5, and 1·5, respectively. We detected stereotype behaviour neither in rats receiving intravenous doses 3 times greater nor in animals injected intraperitoneally with 44, 62 and 112 μmol/kg of (±)‐p‐chloramphetamine, aminorex and phenmatrazine, respectively.
The latter doses of the three amphetamine congeners were tested for their action on tissue monoamine content. Only (±)‐p‐chloramphetamine decreased the concentration of tel‐diencephalon 5‐hydroxytryptamine (5‐HT) and this decrease lasted longer than 24 hours. This and the other two amphetamine congeners failed to affect the concentration of noradrenaline (NA) in brain, heart and lung.
Aminorex (1·5 μmol/kg i.v.) and (±)‐p‐chloramphetamine (3·5 μmol/kg i.v.) decreased the turnover time of striatum dopamine (DM) but failed to change the turnover time of tel‐diencephalon and brainstem NA. Phenmetrazine (5·6 μmol/kg i.v.) changed neither the turnover time of striatum DM nor that of NA in the two brain areas assayed.
Some neurochemical effects of amphetamine, methylamphetamine and p‐bromomethylamphetamine in the rat
Authors: LEONARD B. E. , SHALLICE SUSAN A. 
Published: July 2012

Summary
Low doses of d‐amphetamine increased brain noradrenaline concentrations in the rat; doses greater than 5 mg/kg, however, caused a decrease. Methylamphetamine also showed this dual effect, but a reduction in brain noradrenaline concentration only occurred when doses greater than 10 mg/kg were administered. p‐Bromomethylamphetamine did not significantly reduce brain noradrenaline concentrations even at a dose of 60 mg/kg. The order of potency in reducing the concentration of noradrenaline correlated with the central stimulant effects; d‐amphetamine produced the greatest and p‐bromomethylamphetamine the least increase in motor activity.
d‐Amphetamine and d‐methylamphetamine potentiated the action of 4,α‐dimethyl‐m‐tyramine (H77/77) in depleting brain noradrenaline; the greatest potentiation was produced by d‐amphetamine. This suggests that the phenylethylamines may affect brain noradrenaline concentrations by acting on the reserpine resistant uptake mechanism.
Differences were found in the effect of the three drugs on brain dopamine concentrations; d‐amphetamine caused a decrease while p‐bromomethylamphetamine caused an increase. Methylamphetamine had no effect on the concentration of dopamine. Only p‐bromomethylamphetamine significantly reduced the depletion of brain dopamine concentrations caused by H77/77.
Methylamphetamine and p‐bromomethylamphetamine reduced the concentration of 5‐hydroxytryptamine (5‐HT) in the brain; administration of the same dose of d‐amphetamine did not change the concentration of 5‐HT.
Changes in the blood and brain concentrations of tyrosine and tryptophan, and in the concentration of γ‐amino‐n‐butyric acid in the brain could not be correlated with the changes observed in the concentrations of biogenic amines in the brain.
Secondary excitation of intestinal smooth muscle
Authors: FURNESS J. B. 
Published: July 2012

Summary
A period of stimulation of intrinsic or extrinsic nerves to intestinal muscle is often followed by a secondary contraction. In the present work, the basis for such secondary contractions in the longitudinal muscle of the large bowel of guinea‐pigs and rabbits was examined.
In general, the action of cholinergic nerves did not contribute significantly to the secondary contractions. Concentrations of atropine or hyoscine, which completely blocked primary cholinergic contractions, potentiated or did not significantly reduce secondary contractions.
Atropine resistant, nerve mediated primary contractions of the guinea‐pig ileum were inhibited by anticholinesterases, although these drugs potentiated secondary contractions in other segments of the gut.
The occurrence of a secondary contraction following inhibition of smooth muscle activity did not depend on the nature of the initial inhibition. Thus, secondary contractions were observed following the responses to both non‐adrenergic and adrenergic inhibitory nerves, adenosine triphosphate, noradrenaline and brief periods of anoxia. The secondary contractions following hyperpolarizing drugs or anoxia were not prevented by tetrodotoxin in a concentration sufficient to paralyse all nerves.
It is concluded that cholinergic nerves do not contribute significantly to secondary contractions except at frequencies of stimulation higher than about 50 Hz or after the inhibition of cholinesterases. In the segments of gut examined, the secondary contractions were principally myogenic.
Effects of nicotine on salivary amylase secretion from rabbit parotid gland
Authors: INOKI R. , KOJIMA S. , TAMARI Y. , YAMAMOTO I. 
Published: July 2012

Summary
The effects of nicotine on amylase secretion induced by auriculo‐temporal nerve stimulation were studied.
Nicotine caused a transient increase in secretion as well as flow rate of amylase.
No difference in nicotine action was found between acute sympathetic decentralization of the gland and acute denervation.
The increase in amylase secretion due to nicotine was not inhibited by phenoxybenzamine, bretylium and chronic denervation, but was prevented by hexamethonium, propranolol and adrenalectomy.
The increase in flow rate due to nicotine was not inhibited by propranolol, chronic denervation and adrenalectomy, but was prevented by hexamethonium, phenoxybenzamine and bretylium.
These results show that the action of nicotine in increasing amylase secretion is neither a direct action on the ganglion nor on the nerve terminal of the cervical sympathetic nerve, but is an indirect action of catecholamines released from the adrenal medulla on the post‐junctional receptors.
The study also suggests that the initial acceleration of salivary flow due to nicotine is characterized by a mechanism different from that of amylase secretion.
Some endocrinological aspects of barbiturate dependence
Authors: NORTON P. R. E. 
Published: July 2012

Summary
Hypophysectomized rats become dependent on barbitone and show the same withdrawal syndrome as intact animals.
Barbitone dependent rats have larger thyroid and adrenal glands, a larger liver, smaller gonads and larger secondary sex organs than untreated animals. The levator ani muscle of the males is smaller.
In contrast, dependent female hypophysectomized rats only showed a decreased gonad weight and increased liver weight.
Histologically, the thyroid gland of dependent rats appears more active, but the concentration of iodine bound to plasma protein, basal metabolic rate and body temperature are similar in dependent and untreated animals.
Resting plasma corticosterone concentration appears to be unchanged in barbitone dependent animals, but stress induced increases in the concentration of corticosterone in plasma are less in dependent animals.
Immature barbitone dependent rats grow at a faster rate than untreated animals, but hypophysectomized rats of similar age receiving barbitone do not.
The additional body weight gained by barbitone dependent animals is of normal body composition.
Administration of growth hormone has an identical growth inducing effect in dependent hypophysectomized animals and in untreated hypophysectomized animals.
Barbitone dependent rats do not exhibit the ‘frustration effect’ in a double runway. In barbitone dependent rats approach to a potentially ‘frustrating’ situation is slower than in untreated animals.
Effects of adrenaline on nerve terminals in the superior cervical ganglion of the rabbit
Authors: CHRIST D. D. , NISHI S. 
Published: July 2012

Summary
Adrenaline decreases the release of transmitter from the presynaptic nerves in the superior cervical ganglion of the rabbit. The presynaptic mechanism of adrenaline action was investigated with micro‐electrode techniques.
Adrenaline (10−5M) did not change the threshold of the presynaptic nerve terminals to a current stimulus.
The effect of adrenaline on the excitatory postsynaptic potential (e.p.s.p.) was decreased when the calcium concentration of the perfusing solution was increased to 10 mm.
The effect of adrenaline on a train of e.p.s.ps (30–50 Hz) was analysed. Adrenaline decreased the readily available stores of transmitter, but only slightly changed the probability of release.
The probability of release was increased when the calcium concentration was increased to 5 mm.
It was concluded that adrenaline acts directly on excitation release coupling in the presynaptic terminals.
Influence of the duration of experimental fever on salicylate antipyresis in the rabbit
Authors: CRANSTON W. I. , LUFF R. H. , RAWLINS M. D. , WRIGHT V. ANN 
Published: July 2012

Summary
Steady state fever has been produced in rabbits with a priming injection followed by a sustaining infusion of homologous plasma containing endogenous pyrogen (EP). This fever appears to last as long as the infusion continues.
Intravenous salicylate given 1 h after the start of the EP infusion produced only a small antipyretic effect. The same dose of salicylate given 4 h after the start of an EP infusion resulted in rapid and progressive defervescence. Intermediate antipyretic responses were obtained when salicylate was administered intravenously 2 and 3 h after the start of an EP infusion.
Less than 1% of the systemic dose, when injected into a lateral cerebral ventricle, produced a significantly smaller response at 1 h than at 4 h after the start of an EP infusion. At both these times the fall in temperature following the intraventricular salicylate injection was dose dependent, but the slope of the dose‐response line was significantly steeper at 4 h than at 1 hour.
It is suggested that salicylates produce their antipyretic effects by antagonizing the action of EP within the nervous system, and that the hypothalamic EP concentration falls during the course of an EP infusion.