bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE PHARMACOLOGY OF CHYMOTRYPSIN ADMINISTERED BY INHALATION
Authors: GOLBERG L. , MARTIN L. E. , SHEARD P. , HARRISON C. 
Published: July 2012

The ability of chymotrypsin to reach the limits of the bronchial tree has been studied in cats receiving the enzyme by inhalation as a very fine powder. For this purpose derivatives of chymotrypsin were used which had been labelled with a fluorescent molecule or with [131I]. Quantitative measurements of the absorption and distribution of inhaled chymotrypsin‐ [131I] revealed a rapid removal of radioactivity from the lungs over the first 24 hr. and corresponding excretion of labelled inorganic iodide in the urine. High levels of activity were not attained in the blood or thyroid. Subcutaneous administration of labelled enzyme led to more rapid accumulation of radioactivity in the blood and thyroid. Consideration of these and other results leads to the conclusion that, while some enzyme ascends the respiratory tract by ciliary movement of mucus, a substantial part is absorbed into the lungs and the [131I] subsequently detached from it.The changes in tidal air accompanying inhalation of labelled trypsin and chymotrypsin were followed in anaesthetized cats. Trypsin brings about a decrease in tidal air in distinctly lower doses than does chymotrypsin. Prior administration of mepyramine had an antagonistic effect, and it is suggested that the change in tidal air is essentially the result of bronchial spasm.
THE EFFECT OF ENZYME INHIBITORS ON HISTAMINE CATABOLISM IN MAN
Authors: LINDELL S. E. , NILSSON KAREN , ROOS B.‐E. , WESTLING H. 
Published: July 2012

The catabolism of histamine was studied in three female psychiatric patients by analysis of the [14C]‐labelled metabolic products occurring in the urine after a subcutaneous injection of [14C]histamine. Each patient was studied before and during treatment with aminoguanidine or iproniazid.Without treatment the patients had a normal histamine catabolism. Aminoguanidine and iproniazid inhibited the oxidation of histamine to imidazoleacetic acid; iproniazid produced a 50% inhibition of the oxidation of methylhistamine to methylimidazoleacetic acid. After iproniazid a large proportion of the injected [C14]histamine was excreted as methyl [14C]histamine.
EFFECTS ON AMINE OXIDASE OF SUBSTANCES WHICH ANTAGONIZE 5‐HYDROXYTRYPTAMINE MORE THAN TRYPTAMINE ON THE RAT FUNDUS STRIP
Authors: BARLOW R. B. 
Published: July 2012

Certain substances, 2‐bromolysergic acid diethylamide, dimethyltryptamine (3‐(2‐dimethylaminoethyl)indole), 2‐methyldimethyltryptamine (3‐(2‐dimethylaminoethyl)‐2‐methylindole), and 5‐benzyloxydimethyltryptamine (5‐benzyloxy‐3‐(2‐dimethylaminoethyl)indole), antagonize the effects of 5‐hydroxytryptamine on the rat fundus strip more than those of tryptamine. These substances have been tested for their ability to inhibit the oxidation of tryptamine and 5‐hydroxytryptamine by suspensions of guinea‐pig liver and rat fundus. 2‐Bromolysergic acid diethylamide has virtually no inhibitory activity and it is doubtful if the others produce any significant inhibition of amine oxidase in the concentrations which antagonize the effects of 5‐hydroxytryptamine more than those of tryptamine. It seems that the differential character of the blocking action of these compounds should be ascribed either to interference with the transport of tryptamine (but not 5‐hydroxytryptamine) through the cell wall, coupled with the block of a receptor common to both tryptamine and 5‐hydroxytryptamine, or to the existence of separate tryptamine and 5‐hydroxytryptamine receptors.The amine oxidases of the guinea‐pig liver and rat fundus appear to be a mixture of at least two types of enzyme, one of which has a higher affinity for 5‐hydroxytryptamine than the other and is more susceptible to inhibition by 2‐methyldimethyltryptamine.
ACTIONS OF AMINO‐ACIDS ON THE ISOLATED HEMISECTED SPINAL CORD OF THE TOAD
Authors: CURTIS D. R. , PHILLIS J. W. , WATKINS J. C. 
Published: July 2012

The actions of a series of amino‐acids related to γ‐aminobutyric acid and glutamic acid have been determined upon the isolated and sagittally hemisected spinal cord of the toad, Bufo marinus. Slow and fast components of the ventral root reflex responses following dorsal root stimulation were depressed by γ‐aminobutyric acid and by a series of neutral amino‐acids having a similar structure. The relative depressant potencies of the members of this series were determined by comparison of the concentrations of each required to cause the same reduction in the electrically integrated slow components of these reflex responses. Glutamic acid and closely related substances facilitated reflex responses in low concentrations and depressed these responses in high concentrations. The actions of these substances resulted in the depolarization of motoneurones which was recorded as a negative potential in the ventral root. The relative potencies of the substances were estimated from the concentrations of each required to produce negative potentials of the same magnitude.Several amino‐acids not previously tested proved to have remarkably strong actions on this preparation. 3‐Aminopropanesulphonic acid was the most potent depressant tested; homocysteic acid and n‐methylaspartic acid were the most powerful excitatory substances. The d forms of optically active depressants or excitants were always stronger than the corresponding l forms where both enantiomorphs were available. Points of similarity and dissimilarity between these results and those of related investigations are discussed.
The effects of drugs inhibiting catecholamine uptake on tyramine and noradrenaline‐induced contractions of the isolated rat vas deferens
Authors: BARNETT A. , SYMCHOWICZ S. , TABER R. I. 
Published: July 2012

. Cocaine did not antagonize the tyramine‐induced contractile response of the isolated rat vas deferens at the same concentrations which markedly potentiated the contractile response to noradrenaline.
. Imipramine and amitriptyline non‐competitively antagonized the contractile response to tyramine but did not potentiate noradrenaline. Desmethylimipramine produced both potentiation of noradrenaline and antagonism of tyramine.
. Dexchlorpheniramine non‐competitively antagonized the contractile response to tyramine. It also produced an atypical potentiation of noradrenaline in which lower concentrations of noradrenaline were potentiated to a greater extent than higher ones.
. Imipramine inhibited the in vitro uptake of noradrenaline‐3H in rat vas deferens as did cocaine, desmethylimipramine and dexchlorpheniramine. These results suggest that the α‐adrenergic blocking property of imipramine masks the potentiation of noradrenaline by uptake inhibition.
. Evidence is also presented which suggests that α‐adrenergic blockade of released noradrenaline may be the major mechanism for tyramine inhibition by imipramine‐like drugs. This may explain why cocaine, which has no real alpha blocking action, is ineffective against tyramine.
In vitro studies on the mechanism of kinin formation by trypanosomes
Authors: BOREHAM P. F. L. 
Published: July 2012

. An investigation into the mechanism of kinin release in trypanosomiasis has been made in vitro.
. Trypanosomes contain a low level of kininase but no kinin‐forming enzyme nor substrate for salivary kallikrein.
. The kininase activity in the plasma of infected rats does not differ from that of normal animals, and trypanosomes do not affect the breakdown of synthetic bradykinin by enzymes in the blood.
. In trypanosomiasis the kininogenase precursor in plasma is activated. The hypothesis is put forward that the antigen‐antibody complex may be involved in this.
Sensitization of smooth muscle to plasma kinins: effects of enzymes and peptides on various preparations
Authors: EDERY H. , GRUNFELD Y. 
Published: July 2012

The influence of various materials, principally hydrolases and peptides, on the sensitivity to stimulating substances has been studied in a wide range of isolated and in vivo smooth muscle preparations.
Chymotrypsin raised the susceptibility of the guinea‐pig isolated ileum to peptides related to bradykinin and also sensitized isolated ileum and fundus of rat and albino gerbil to bradykinin. No sensitization to the kinin occurred in the following preparations: rat, gerbil and rabbit duodenum; rat colon and urinary bladder; dog tracheal chain; and rabbit jejunum. Chymotrypsin and peptides structurally related to the active centre of the enzyme did not affect the permeability increasing property of bradykinin in guinea‐pig skin microcirculation vessels. In contrast, intravenously administered chymotrypsin markedly augmented the bronchoconstrictor action of the kinin.
Ficin and pronase increased the sensitivity of guinea‐pig ileum to bradykinin. Pronase also sensitized the gerbil ileum and this effect was abolished by previous treatment with di‐isopropylfluorophosphonate (dyflos). Pronase destroyed bradykinin after incubation.
Reduced glutathione potentiated the response to bradykinin of guinea‐pig ileum but did not affect its sensitivity. The potentiation also occurred in a chymotrypsin‐treated preparation.
It is assumed that specific sensitization elicited by proteinases might derive from an effect on the protein envelope of smooth muscle membrane.
Post‐tetanic and drug‐induced repetitive firing in the soleus muscle of the cat
Authors: BOWMAN W. C. , GOLDBERG A. A. J. , RAPER C. 
Published: July 2012

The effects of a high frequency indirect tetanus on the responses to subsequent infrequently applied nerve shocks have been compared in the tibialis anterior and soleus muscles of cats and rabbits.
Post‐tetanic augmentation of twitches in the cat soleus muscle was shown to be partly due to repetitive firing and partly due to increased synchronization of the muscle fibre response. Post‐tetanic repetitive firing was not evident in the responses of the other three muscles studied.
Post‐tetanic repetitive responses in the cat soleus muscle and nerve did not originate in the nerve trunk and were not produced by direct muscle stimulation; they were abolished by doses of tubocurarine smaller than those necessary to reduce the twitch tension below the pre‐tetanic level. These findings support the conclusion of others that the repetitive firing originates at the neuromuscular junction.
The repetitive firing could not be explained by an increase in the sensitivity of the motor endplates to acetylcholine, suggesting that an increase in and/or a prolongation of the output of transmitter from the motor nerve contributes to it.
The cat soleus muscle was shown to be more sensitive to neostigmine than were the other three muscles studied, and acetylcholinesterase determinations showed that this muscle possesses less enzyme activity.
It is concluded that an increase in transmitter output, coupled with a weaker cholinesterase activity, probably accounts for the post‐tetanic repetitive activity in the cat soleus muscle.
Post‐tetanic repetitive firing was absent in cat soleus muscles which had been cross‐innervated with the nerve formerly innervating a fast‐contracting muscle.
The accumulation of guanethidine by human blood platelets
Authors: BOULLIN D. J. , O'BRIEN R. A. 
Published: July 2012

When human blood platelets were incubated aerobically in plasma containing 2 × 10−7 to 10−3M radioactive guanethidine for 10 min to 6 hr, the drug was accumulated against a concentration gradient until concentration ratios (platelet/plasma) of up to 80: 1 were obtained.
The decline in rate of uptake after 3 hr appeared to result from a decrease in platelet viability, because accumulation was reduced by prolonged incubation before addition of guanethidine.
Uptake was energy‐dependent because it was inhibited by cold and ouabain.
Sodium ions were essential for guanethidine uptake and retention of 5‐hydroxytryptamine (5‐HT).
Accumulation was inhibited by 5‐HT, desipramine, cocaine, dexamphetamine, bretylium, tyramine and noradrenaline; bethanidine, p‐chlorophenylalanine and (–)‐α‐methyldopa were inactive.
Guanethidine was tightly bound to platelets, only 10% being lost from labelled cells during 60 min incubation in drug‐free plasma; but efflux was increased by addition of amphetamine.
The binding sites for guanethidine seemed to be different from those for 5‐HT since guanethidine accumulation was independent of 5‐HT levels, and neither guanethidine uptake or release were affected by reserpine.
Guanethidine was not metabolized by platelets or plasma in vitro.
We consider that, if our results regarding uptake, binding and release of guanethidine are confirmed in vivo, and also found to apply to other pharmacologically active agents, then the eventual loss of a platelet‐bound substance may increase pharmacological action by raising plasma levels.
Decrease in ionic permeability of the cell membrane in guinea‐pig atrial tissue by treatment with antifibrillatory agents and hexobarbitone, determined by means of 86Rb
Authors: ZWIETEN P. A. van 
Published: July 2012

The influence of antifibrillatory agents on the release of previously accumulated 86Rb+ ions was studied in guinea‐pig isolated left auricles, incubated in a K+‐free Tyrode solution that contained an equivalent concentration (2.7 mm) of Rb+. The auricles were stimulated electrically at a frequency of 100/min and showed entirely “normal” mechanical behaviour in the incubation medium.
Quinidine, tetracaine, hexobarbitone‐Na and propranolol caused a dose‐dependent negative inotropic effect. The frequency of beating (100/min) was usually not affected by these drugs.
The reduction in contractile force was accompanied by a dose‐dependent inhibition of 86Rb release. The concentration‐response curves for both the mechanical effect and the influence on 86Rb release almost coincided for quinidine, although these curves diverged for the other drugs studied.
It is suggested that all the four different antifibrillatory drugs cause a general reduction of the membrane permeability to inorganic ions. The mechanism of this membrane stabilization remains unknown.
Combined effect of sodium maleate and some thiol compounds on mercury excretion and redistribution in rats
Authors: MAGOS L. , STOYTCHEV T. 
Published: July 2012

(+)‐Penicillamine in a dose of 193 μmoles/kg given subcutaneously twice a day on the sixth and seventh days after the administration of 100 μg mercury increased the urinary excretion of rats more than the equimolar dose of N‐acetyl‐(+)‐penicillamine but less than 2,3‐dimercaptopropanol 48.3 μmoles/kg.
Sodium maleate in a dose of 156 μmoles/kg given on the sixth and seventh days after the mercury did not influence mercury excretion or redistribution. Sodium maleate in the same dose increased considerably the effect of (+)‐penicillamine on the urinary excretion and redistribution of mercury. It increased the effect of N‐acetyl‐(+)‐penicillamine only slightly. There was a tendency to decrease the effect of 2,3‐dimercaptopropanol.
All the complexing agents decreased the kidney content of mercury and increased the liver and blood concentration of mercury. These changes were highest with 2,3‐dimercaptopropanol. The combination of sodium maleate with (+)‐pencillamine caused higher mercury excretion and lower kidney content but a smaller increase in the liver and blood mercury contents than 2,3‐dimercaptopropanol.
Antagonism of the response of human isolated arteries to noradrenaline
Authors: BIRMINGHAM A. T. , ERNEST K. , NEWCOMBE J. F. 
Published: July 2012

Spirally‐cut strips from human visceral arteries isolated in vitro were contracted by noradrenaline and this contraction was antagonized by the α‐receptor blocking agent, thymoxamine.
The cumulative log dose‐response curves to noradrenaline in the presence of thymoxamine were moved to the right of and parallel to the curve for noradrenaline alone. The blockade was surmountable and reversible.
The quantitative criteria for simple competitive antagonism were satisfied. When log (x − 1) was plotted against pAx the points fitted a straight line with a slope (− n) of 0.91. The pA2 for thymoxamine was 7.54 and the mean value for log K2 was 7.82. These values are in approximate agreement with those previously reported for animal isolated arterial strips.
Inhibition by lidoflazine of the contractile response of the rat isolated colon to angiotensin
Authors: ELLIS D. E. , REIT E. 
Published: July 2012

In the rat isolated ascending colon, lidoflazine in a concentration of 5 × 10−7M slightly enhanced the response to angiotensin, but in a concentration of 10−6M it was a strong and unsurmountable antagonist.
Exposure to lidoflazine (10−6M) also inhibited the contractile responses to acetylcholine, 5‐hydroxytryptamine and barium ions. The antagonism of acetylcholine and 5‐hydroxytryptamine was unsurmountable and quantitatively similar to that of angiotensin. The antagonism of barium ions was much weaker and probably competitive.
The inhibitory effect of papaverine (10−5M) showed a pattern similar to that found for lidoflazine.
It is concluded that the antagonism of angiotensin by lidoflazine in the rat colon is non‐specific.
The pharmacology of a new oxytocic principle from ox hypothalamus
Authors: HAWKER R. W. , NORTH W. G. , ZERNER B. 
Published: July 2012

An oxytocic substance has been isolated from ox hypothalamus by successive gel filtration on Sephadex G‐25 and Sephadex G‐50, and its pharmacology has been examined on three smooth muscle preparations.
The substance has the same order of potency on rat uterus, guinea‐pig ileum, and hen rectal caecum.
The action of the substance on rat uterus was not abolished by thioglycollate.
Atropine (1.0 μg/ml.), phenoxybenzamine (0.1 μg/ml.) and mepyramine (1.0 μg/ml.) did not block the smooth muscle action of the substance.
Drug action, relative potency, and log dose‐response relationships distinguish the substance from 5‐hydroxytryptamine, acetylcholine, oxytocin, vasopressin, angiotensin amide, bradykinin, and purified preparations of substance P.
Some effects of Pco2 and pH on nerve tissue
Authors: ELLIS F. R. 
Published: July 2012

Rat phrenic nerve preparations were used in vitro to study action potential amplitude and nerve conduction time under varying conditions of Pco2 and sodium bicarbonate concentration in the surrounding Krebs solution.
A correlation was found between action potential amplitude and pH but not between action potential amplitude and Pco2.
A better correlation was found between conduction time and pH than between conduction time and Pco2.
Catecholamine and 5‐hydroxyindole metabolism in immunosympathectomized rats
Authors: CEASAR P. M. , RUTHVEN C. R. J. , SANDLER M. 
Published: July 2012

The daily urinary excretion of normetadrenaline, metadrenaline, 4‐hydroxy‐3‐methoxyphenylglycol, 4‐hydroxy‐3‐methoxymandelic acid, dopamine, homovanillic acid, 5‐hydroxytryptamine and 5‐hydroxyindolylacetic acid has been estimated in the urine of immunosympathectomized and control rats.
A method is given which allows separate spectrophotometric determination of 4‐hydroxy‐3‐methoxyphenylglycol and 4‐hydroxy‐3‐methoxymandelic acid in the same sample of rat urine. Metadrenaline and normetadrenaline were estimated by a modification of the method of Anton & Sayre (1966).
Approximately 17% of the 4‐hydroxy‐3‐methoxymandelic acid in rat urine is excreted in the free state, over 60% as a glucuronide conjugate and the remainder as a sulphate conjugate.
Urinary excretion of 4‐hydroxy‐3‐methoxyphenylglycol was approximately halved in immunosympathectomized rats (P>0.001). 4‐Hydroxy‐3‐methoxymandelic acid output was significantly increased in treated animals (P>0.05) when expressed in terms of body weight. No significant difference was detected for any of the other compounds investigated.
The results are discussed in the light of previous knowledge of the effect of immunosympathectomy on catecholamine metabolism.
The effect of cocaine and imipramine on tyramine‐induced release of noradrenaline‐3H from the rat vas deferens in vitro
Authors: BARNETT A. , STAUB M. , SYMCHOWICZ S. 
Published: July 2012

Tyramine 10−4m significantly increased release of noradrenaline‐7–3H (NA‐7–3H) from rat vas deferens in vitro.
Neither cocaine 10−5m nor imipramine 10−7m–10−6m significantly reduced tyramine‐induced release of NA‐7–3H.
Increasing the exposure time to cocaine and imipramine from 10 to 20 min or pre‐incubating the tissue with a wide range of NA‐7–3H concentrations (3.3–333.3 ng/ml.) did not affect the lack of inhibition by cocaine and imipramine.
It is suggested that the tyramine receptor in rat vas deferens differs from that in other systems and that blockade of tyramine‐released noradrenaline at α‐adrenergic receptors may be the most important mechanism for tyramine antagonism by imipramine‐like drugs in this tissue.
The interactions of noradnamine and imipramine‐like antidepressant drugs
Authors: COWELL PAULINE 
Published: July 2012

The hypothesis of Roberts & Broadley (1965) that noradnamine formation in the brain is responsible for endogenous depression has been investigated in mice.
Injections of noradnamine given directly into the lateral ventricles caused convulsions and profound hypothermia, but were without effect if given subcutaneously.
The hypothermia, but not the convulsions, induced by noradnamine was reversed by imipramine‐like antidepressant drugs given before or after the injection of noradnamine. The convulsions but not the hypothermia were abolished by phenobarbitone.
Increasing doses of nortriptyline produced a parallel shift of the hypothermic log dose‐response curve for intraventricular injections of noradnamine to the right.
The minimal effective dose of nortriptyline required to reverse noradnamine hypothermia was the same whether the nortriptyline was injected directly into the lateral ventricle or subcutaneously.
No evidence was found to substantiate the claim that reserpine hypothermia is mediated by noradnamine formation in the brain.
Intraventricular, but not intraperitoneal, injection of noradnamine caused a depletion of brain noradrenaline and an increase in brain 5‐hydroxytryptamine. These changes did not result from the convulsive activity and were not modified by pretreatment with nortriptyline. No effect on heart noradrenaline levels was recorded.
Noradrenaline, given subcutaneously, also antagonized the hypothermic response to noradnamine.
The reversal of noradnamine hypothermia by both noradrenaline given subcutaneously and nortriptyline was blocked by α and β‐adrenoeeptive receptor blocking agents.
It is considered that the mode of action of the antagonism of noradnamine hypothermia by imipramine‐like antidepressant drugs is a peripheral and not a central mechanism and probably results from a potentiation of the effects of circulating noradrenaline released by noradnamine.
The effects of anions on sodium transport
Authors: CUTHBERT A. W. , PAINTER ELISABETH , PRINCE W. T. 
Published: July 2012

Substitution of chloride by isethionate reduces the short circuit current (SCC) and increases the potential of isolated frog skin. In sodium isethionate Ringer antidiuretic hormone and choline chloride increase the SCC, whereas theophylline is ineffective.
Frog skins treated on the outside with copper ions always show an increased potential when bathed in normal Ringer solution. The SCC may be moderately increased or decreased.
Theophylline increases skin thickness and cell volume in non‐short‐circuited skins.
The ways in which the theophylline‐induced increase in chloride permeability affects sodium transport is discussed, together with the requirements for a permeant anion in both short‐ and open‐circuited skins.