bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of isoprenaline and aminophylline on the chronotropic responses of the isolated guinea‐pig heart to vagal stimulation and acetylcholine
Authors: HADHAZY P. 
Published: July 2012

Summary
In isolated perfused guinea‐pig hearts, isoprenaline (2 × 10−8 g/ml) reduced the negative chronotropic responses to vagal stimulation and to exogenous acetylcholine.
The β‐adrenoceptor antagonist LB46 (2 × 10−8 g/ml) abolished the effect of isoprenaline in reducing vagal bradycardia. LB46 itself did not alter the responses to vagal stimulation.
Increase in 86Rb efflux induced by acetylcholine was not affected by isoprenaline.
Aminophylline (2·3 × 10−4 g/ml) almost abolished the negative chronotropic effect of vagal stimulation.
The ‘antivagal’ effects of isoprenaline and aminophylline may be at a common site beyond the level of the cardiac β‐adrenoceptors, perhaps related to cyclic‐3′,5′‐AMP and/or sodium transport.
Temperature dependence of catecholamine depletion by reserpine in the heart of the toad (Bufo marinus)
Authors: CHANG P. , RAND M. J. 
Published: July 2012

Summary
The catecholamines in toad ventricle were adrenaline (90%) and noradrenaline (10%); there was no dopamine.
Phenoxybenzamine and tyramine stimulated the isolated heart and reduced the catecholamine content.
Reserpine treatment of toads kept at 20° C did not affect the adrenaline but reduced the noradrenaline content of the ventricle.
At 37° C, reserpine caused depletion of both adrenaline and noradrenaline, and the stimulant actions of phenoxybenzamine and tyramine were lost.
Techniques for measuring histamine formation in mice
Authors: REILLY MARGARET A. , SCHAYER R. W. 
Published: July 2012

Summary
Formation of 14C‐histamine from 14C‐l‐histidine was studied in mice using various inhibitors of histamine catabolism; these included aminoguanidine, pargyline and methylhistamine, inhibitors of diamine oxidase, monoamine oxidase, and the histamine‐methylating enzyme, respectively.
Four general approaches were used: inhibiting diamine oxidase and the histamine‐methylating enzyme and measuring 14C‐histamine in tissues or urine, or inhibiting diamine oxidase and monoamine oxidase and measuring 14C‐methylhistamine in tissues or urine. In some tests mice with normal concentrations of histidine decarboxylase were used; in others the enzyme was activated by pretreating mice with Freund's adjuvant.
Methylhistamine pretreatment increased 14C‐histamine in several tissues of mice but aminoguanidine had no significant effect; it was concluded that endogenously formed histamine is inactivated almost entirely by methylation.
There was no evidence of parallelism between the ability of tissues to form histamine and to inactivate endogenous histamine.
Effects of Freund's adjuvant on tissue concentrations of 14C‐histamine were tested in mice with or without inhibitors of histamine catabolism. Results were essentially parallel in both cases but higher in the former.
The method of choice is measurement of 14C‐histamine in tissues of mice given aminoguanidine and methylhistamine, followed by 14C‐l‐histidine.
Other approaches listed above may be useful but require improvement, for example, a more specific assay for 14C‐methylhistamine and a stronger, longer‐lasting inhibitor of histamine‐methylation.
In vivo effects of cellulose sulphate on plasma kininogen, complement and inflammation
Authors: EISEN V. , LOVEDAY C. 
Published: July 2012

Summary
The in vivo action of cellulose sulphate was studied in an attempt to clarify the role of complement and kinin formation in inflammation.
Inflammatory oedema was produced in the rat paw by heat (45·5° C), and on the ear by xylene. The oedema was assessed by comparing the ratio of fresh wet weight to dry weight of corresponding injured and non‐injured parts.
Following cellulose sulphate (6·5 mg/kg i.v.), plasma kininogen concentrations were promptly reduced by 90% or more. The reduction in complement titres was statistically significant and ranged from 17 to 65%. No toxic effects were observed. The oedema caused by heat or xylene was not reduced in these rats.
Cellulose sulphate (80 mg/kg i.p.) given over 3 days depleted plasma kininogen by about 90%, but reduced complement titres only slightly. These rats gained less weight and their condition was poor. Blood clotting was impaired and widespread haemorrhages were found. Heat and xylene produced significantly less oedema than in control rats. This diminished response is attributed to toxic side effects of cellulose sulphate, rather than depleted plasma kininogen and reduced plasma complement.
The results suggest that the inflammatory reactions to thermal and chemical injury can fully develop when plasma kininogen and complement are lowered.
Effect of eserine on the chick biventer cervicis preparation
Authors: BALDWIN D. W. , LESSER E. 
Published: July 2012

Summary
The relationship between the capacity of the chick biventer preparation, both intact tissue and homogenate, to inactivate acetylcholine and the ability of eserine to increase the sensitivity of the tissue to acetylcholine have been investigated.
At concentrations of eserine of 2·69 × 10−9m and 2·69 × 10−8m the capacity of the whole tissue to inactivate acetylcholine is reduced by 5% and 15% respectively. These concentrations of eserine increase the sensitivity of the preparation to acetylcholine by factors of 2 and 4 respectively, without a change of slope in regression lines.
At concentrations of eserine of 2·69 × 10−7m and 2·69 × 10−6m the capacity of the whole tissue to inactivate acetylcholine is reduced by 40% and 80% respectively, and the sensitivity to acetylcholine increased by factors of 70 and 800 respectively, along with marked increases in the slopes of the regression lines.
An attempt has been made to quantify these differences by proposing a model in which cholinesterase in the tissue is regarded as a network, preventing the access of a large fraction of the acetylcholine to its site of action.
It is suggested that, whereas the increase in sensitivity to acetylcholine at eserine concentrations of 2·69 × 10−9m and 2·69 × 10−8m can be interpreted as an anticholinesterase effect (which is still present at higher concentrations), that seen at the higher concentrations may represent a direct action of eserine on the tissue.
It is further suggested that there are barriers to penetration in intact tissue to both substrate and inhibitor, which invalidate attempts to extrapolate results from homogenates.
Binding of N‐(2‐bromo ethyl)‐N‐ethyl‐N1‐naphthylmethylamine HBr (SY28) to the proteins of guinea‐pig vas deferens
Authors: GRAHAM J. D. P. , MOTTRAM D. R. 
Published: July 2012

Summary
Vasa deferentia from guinea‐pigs were exposed to 14C‐SY28 HBr (5·32 × 10−6m) washed, lipid extracted, and broken up.
The tissue was digested with papain, hydrolyzed with 6 n HCl, and gel filtration performed.
Aliquots at each stage were used for paper chromatography and autoradiography.
Three labelled spots (in addition to unbound 2‐halogenoalkylamine) were located from acid hydrolysate and a fourth from gel filtrate.
Selected amino‐acids were complexed with 14C‐SY28 and the procedure repeated. The RF values were compared with those of the same amino‐acids with and without 6 n HCl.
Histidine, aspartic acid, arginine and serine gave a significant degree of binding of 14C‐SY28.
The theoretical implications are discussed.
Actions of acetylcholine and carbachol on the chick biventer cervicis muscle
Authors: MARSHALL I. G. 
Published: July 2012

Summary
The possibility that carbachol may act on the chick biventer cervicis muscle by releasing acetylcholine was investigated.
Log dose‐response curves for acetylcholine and carbachol were constructed in the presence of triethylcholine, tubocurarine and physostigmine, in both innervated and denervated chick biventer cervicis muscles.
The log dose‐response curve for acetylcholine was shallower than that for carbachol and was moved to the left by triethylcholine, indicating potentiation. In the presence of physostigmine, the curve was as steep as that for carbachol, and like that for carbachol was moved to the right by triethylcholine, indicating antagonism. In the presence of tubocurarine, the log dose‐response curves for both acetylcholine and carbachol were moved to the right.
The log dose‐response curves for both acetylcholine and carbachol were moved to the left by chronic denervation, indicating increased sensitivity to these drugs. Both curves were moved similar distances to the right by excess magnesium ion concentration. No tachyphylaxis developed to repeated administration of carbachol in the presence of triethylcholine or tubocurarine, either in innervated or denervated muscles.
It was concluded that the main action of triethylcholine in the chick biventer cervicis muscle is a tubocurarine‐like action, which, in the presence of acetylcholine, is masked by a weak anticholinesterase action. It was also concluded that the diminished response to carbachol in the presence of triethylcholine is due to the postjunctional blocking action of triethylcholine, and that carbachol owes none of its activity to an ability to release acetylcholine from the nerve terminals.
Actions of dexamphetamine and amphetamine‐like amines in chickens with brain transections
Authors: MARLEY E. , STEPHENSON J. D. 
Published: July 2012

Summary
A method for preparing the encéphale isolé preparation in young fowls is described. Certain important differences were found between electrocortical activity of chicken and mammalian encéphale isolé preparations. Electrocortical effects of excitant sympathomimetic amines and their antagonism were readily quantified because of stable electrocortical activity of the chick encéphale isolé preparation.
Amphetamine‐like excitant amines ((+)‐ and (–)‐amphetamine, α‐methyltryptamine, tryptamine, β‐phenethylamine, cyclopentamine, β‐tetrahydronaphthylamine and tuaminoheptane) evoked electrocortical desynchronization in chick encéphale isolé preparations, confirming the central origin of these effects. Behavioural changes were also observed.
The electrocortical response to these amines was antagonized by methysergide, a selective tryptamine antagonist and by a catecholamine, α‐methyl‐noradrenaline. Behavioural changes were also antagonized.
Electrocortical desynchronization to dexamphetamine was prevented by an anterior transection of the brain which separated the telencephalon from the diencephalon. More posterior transections reduced the duration of the electrocortical response to dexamphetamine; intensity of response was either increased or decreased.
Protection against induction of supersensitivity to catecholamines by cocaine
Authors: INNES I. R. , KARR G. W. 
Published: July 2012

Summary
Adrenaline, noradrenaline, isoprenaline, tyramine, phentolamine, pronethalol, histamine and acetylcholine were each tested for their ability to prevent cocaine from causing supersensitivity to catecholamines in cat spleen strips in vitro. A high concentration of one of these drugs was added to the bath 5 min before cocaine hydrochloride (10 μg/ml). The effect on subsequent responses to catecholamines was compared with the effect of cocaine in control strips in the absence of an interfering drug.
Phentolamine completely abolished the potentiating effect of cocaine. Large doses of adrenaline or noradrenaline reduced, but did not completely prevent, potentiation. Tyramine, isoprenaline, pronethalol, histamine and acetylcholine did not prevent potentiation.
The ability of these drugs to interfere with potentiation does not correlate well with their ability to interfere with uptake of noradrenaline. Interference with uptake by cocaine is therefore unlikely to account fully for potentiation.
Effects of methysergide on platelets incubated with reserpine
Authors: CUMINGS J. N. , HILTON BARBARA P. 
Published: July 2012

Summary
Platelets were incubated with methysergide and related compounds (2‐bromo lysergic acid (BOL), ergotamine and methyl ergotamine) together with reserpine.
Methysergide inhibited the normal aggregation response of platelets to 5‐hydroxytryptamine (5HT) but did not affect the reduction in the 5HT content caused by reserpine, or the uptake of 5HT by the platelets.
BOL, ergotamine and methyl ergotamine behaved similarly. Methysergide had greater anti5HT potency than BOL, and methyl ergotamine had greater potency than ergotamine.
The use of platelets as a model for synaptic preparations is discussed.
The role of 5HT receptor sites on the platelet membrane and the significance of the results for migraine patients treated with methysergide are discussed.
Role of noradrenaline and 5‐hydroxytryptamine in tetrahydronaphthylamine‐induced temperature changes in the rat
Authors: BRUINVELS J. , KEMPER G. C. M. 
Published: July 2012

Summary
Intraperitoneal administration of graded doses of tetrahydronaphthylamine (THN) to rats caused a dose dependent decrease in body temperature.
Intracisternal injection of graded doses of THN induced hypothermia, and implantation of crystalline THN rostral to the medial preoptic area and caudal to the striatum, caused hyperthermia.
Pretreatment of the rats with a MAO inhibitor changed the hypothermia into hyperthermia.
Intraperitoneal injection of 5‐hydroxytryptophan caused a hypothermia which could be reversed into hyperthermia when the rats were pretreated with a MAO inhibitor.
Pretreatment with parachlorophenylalanine enhanced the THN‐induced hypothermia.
Depletion of brain monoamines by Ro‐4–1284 in combination with an inhibition of the biosynthesis of noradrenaline (diethyldithiocarbamate) changed the THN‐induced hypothermia into hyperthermia.
It is concluded that THN affects body temperature in rats by two central mechanisms, viz. a decrease mediated by noradrenaline, probably in the hypothalamus, and an increase which might be mediated by 5‐hydroxytryptamine rostral to the medial preoptic area.
Interaction effects of ethanol and pyrazole in laboratory rodents
Authors: BLUM K. , GELLER I. , WALLACE J. E. 
Published: July 2012

Summary
Interactions of pyrazole and ethanol were studied in three laboratory test procedures. They included sleeping time in mice, rotor rod balance in rats and lever pressing behaviour of rats.
Equimolar concentrations of pyrazole and 3‐methylpyrazole were compared for effects on enhancement of ethanol's activity on rotor rod holding time of rats.
Minimally effective doses of pyrazole, the LADH inhibitor, and 3‐methylpyrazole, a non‐inhibitor of LADH, when administered before ethanol, resulted in an increased behavioural depression. These interaction effects are probably not caused by inhibition of LADH but rather by an increase in the direct depressant action of either one or both of the compounds.
Drug‐induced changes in the release of [3H]‐noradrenaline from field stimulated rat iris
Authors: FARNEBO L.‐O. , HAMBERGER B. 
Published: July 2012

Summary
Isolated rat irides were incubated with [3H]‐noradrenaline [3H‐NA] (10−7m), supervised with buffer and then stimulated by an electrical field. The effect of desipramine, clonidine, phentolamine, phenoxybenzamine, GD131, normetanephrine and 4‐tropolone‐acetamide on the stimulation‐induced overflow of [3H]‐NA was tested by adding the drug to the super‐fusing buffer. The effect of pretreatment with phentolamine or phenoxybenzamine on the stimulation‐induced overflow of [3H]‐NA was also studied.
The effect of desipramine, clonidine, phentolamine, phenoxybenzamine and GD131 on uptake of [3H]‐NA in isolated irides was determined.
Desipramine moderately increased the stimulation‐induced overflow at concentrations which almost completely inhibited neuronal uptake. It was calculated that in the isolated rat iris 30–40% of the released [3H]‐NA is inactivated by reuptake into the nerve terminal. This figure may represent the true reuptake percentage in this preparation. Desipramine‐induced inhibition of [3H]‐NA release from the nerve terminal, possibly via a negative feed‐back mechanism, may also contribute to this low figure.
Phentolamine and phenoxybenzamine, in concentrations or doses which did not inhibit neuronal uptake of [3H]‐NA, consistently increased the stimulation‐induced overflow. This increase was further augmented when neuronal uptake was inhibited.
The α‐adrenoceptor stimulating drug clonidine decreased the stimulation‐induced overflow.
GD131, normetanephrine and 4‐tropolone‐acetamide did not greatly affect the stimulation‐induced overflow of [3H‐NA].
It is concluded that the increased [3H]‐NA overflow obtained after α‐adrenoceptor blockade is due to an increased [3H]‐NA release from the nerve terminals.
Neuromuscular blocking activity of a new series of quaternary N‐substituted choline esters
Authors: GINSBURG SARA , KITZ R. J. , SAVARESE J. J. 
Published: July 2012

Summary
The neuromuscular blocking activity of a new group of mono‐ and diquaternary N‐substituted choline esters of several carboxylic acids has been evaluated in various whole animal preparations in the mouse, rat and cat.
A basic non‐depolarizing mechanism was present in all but one compound—a depolarizing agent, which was studied for comparison. There was evidence of facilitatory activity and nicotinic stimulation in the monoquaternary compounds. These effects were diminished in the diquaternary compounds.
The presence of a bulky aromatic ring system on the nitrogen atom appeared to increase both neuromuscular blocking potency and facilitatory activity in the experimental animal. A similar relationship had previously been demonstrated in vitro in another study.
The duration of action, although short in most compounds, did not correlate well with previously determined in vitro hydrolysis rates, possibly because of species differences.
The general pharmacology of each compound appeared to depend considerably upon the structure of the choline moiety.
Interaction of albumin and fusidic acid: Appendix on interaction of albumin and fusidic acid
Authors: GÜTTLER F. , TYBRING L. , ENGBERG‐PEDERSEN H. 
Published: July 2012

Summary
By combining the agar plate diffusion technique for determination of antibiotic activity and zone microelectrophoresis in agar gel, the activity of fusidic acid in individual serum proteins of blood and pus obtained from patients given sodium fusidate revealed albumin to be responsible for the protein binding of this antibiotic.
Based on the assumption that only free fusidic acid is microbiologically active, the relationship between the concentration of albumin and the ratio of free to total fusidic acid was determined at four concentrations of free fusidic acid, using as test organisms four differently sensitive variants of a Staphylococcus aureus strain. At each concentration an increasing amount of albumin (0–40 mg/ml culture medium) decreased the activity of fusidic acid as determined in serial dilutions (IC50).
The law of mass action expressed as Langmuir's adsorption isotherm was valid if a correction for the influence of albumin on the sensitivity of the strain of Staph. aureus was introduced. For other test organisms no correction is necessary. The constant in Langmuir's adsorption isotherm was K = 78400 ± 8200 l./mol and n = 3·15 (95% confidence limits: 2·09–5·52).
The mean blood concentration was 20·8 μg/ml and the mean pus concentration 17·2 μg/ml in nineteen sets of blood and pus samples. The ratio of pus to blood corresponds to the ratio of published values for the protein concentrations in serum and in inflammatory oedema.
It is concluded that for albumin bound drugs the ‘storage depot’ of the organism also includes the fluid of the tissue spaces including the inflammatory oedema. As recent studies have revealed an extravascular albumin pool similar in size to the plasma pool, this ‘storage depot’ should not be neglected.
Noradrenaline uptake by non‐innervated smooth muscle
Authors: BURNSTOCK G. , McLEAN J. R. , WRIGHT MARY 
Published: July 2012

Summary
Uptake of noradrenaline (NA) into the non‐innervated smooth muscle cells of the human umbilical artery and the chick amnion has been studied with the fluorescence histochemical technique for localizing monoamines. Comparison has been made with uptake into sympathetically innervated smooth muscle of the rabbit ear artery.
Accumulation of NA within non‐innervated smooth muscle cells is observed histochemically after exposure to much lower concentrations of NA (10−7 g/ml) than in sympathetically innervated smooth muscle cells, where accumulation occurs with NA (10−5 g/ml).
In contrast to innervated smooth muscle, uptake of NA (10−4 g/ml) by non‐innervated smooth muscle is characterized by lack of inhibition by phenoxybenzamine, normetanephrine and cold, although some inhibition is apparent at lower NA concentrations. Retention of NA during prolonged washing in NA‐free Krebs demonstrates that it is strongly bound within the non‐innervated smooth muscle cells, particularly in the nucleus.
After inhibition of catechol‐O‐methyl transferase, the accumulation of NA in innervated smooth muscle closely resembles that in non‐innervated smooth muscle.
Pharmacology of 4‐hydroxypropranolol, a metabolite of propranolol
Authors: FITZGERALD J. D. , O'DONNELL STELLA R 
Published: July 2012

Summary
4‐Hydroxypropranolol, a metabolite produced after oral administration of propranolol, has been shown to be a β‐adrenoceptor blocking drug. It is of similar potency to propranolol in antagonizing the effects of isoprenaline on heart rate and blood pressure in cats and against isoprenaline protection of guinea‐pigs from bronchospasm. It is not cardioselective.
In rats depleted of catecholamine 4‐hydroxypropranolol produced an increase in heart rate, suggesting that it has intrinsic sympathomimetic activity.
In anaesthetized dogs 4‐hydroxypropranolol produced a decrease in heart rate and dP/dt and an increase in A‐V conduction time at doses within the range 0·09–1·25 mg/kg. These effects are a result of β‐adrenoceptor blockade. In dogs depleted of catecholamines these same doses produced an increase in heart rate and dP/dt and a decrease in A‐V conduction time. These responses were antagonized by propranolol, and were due to the intrinsic sympathomimetic activity of the compound. At higher doses (5·25 and 13·25 mg/kg) a further dose dependent decrease in heart rate and dP/dt and an increase in A‐V conduction time occurred. This trend was also seen in animals depleted of catecholamines. These changes represent membrane stabilizing activity of 4‐hydroxypropranolol.
4‐Hydroxypropranolol is a potent β‐adrenoceptor blocking drug with both intrinsic sympathomimetic activity and membrane stabilizing activity.