bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new dopamine‐β‐hydroxylase inhibitor: effects on the noradrenaline concentration and on the action of L‐DOPA in the spinal cord
Authors: ANDÉN N.‐E. , FUXE K. 
Published: July 2012

Summary
The dopamine‐β‐hydroxylase inhibitor bis(4‐methyl‐1‐homopiperazinyl‐thiocarbonyl) disulphide (FLA‐63; 25 mg/kg i.p.) caused within 4 h a 65% loss of noradrenaline throughout the intact rat spinal cord and also cranial to a transection of the cut spinal cord. Caudal to the lesion, there was only an insignificant depletion of 17% indicating the importance of nerve impulses for the disappearance of noradrenaline.
Dopamine accumulated in the spinal cord after treatment with FLA‐63 although the amounts were not sufficient to replace the missing noradrenaline. Even after treatment with l‐3,4‐dihydroxyphenylalanine (l‐DOPA), the catecholamine store was incompletely replenished by dopamine.
After a large depletion of the noradrenaline stores, induced by repeated doses of FLA‐63 or by reserpine plus FLA‐63, the l‐DOPA‐induced increase in flexor reflex activity of the hind limbs of spinal rats was inhibited much more than after pretreatment with α‐methyl‐tyrosine or reserpine. FLA‐63 blocked the formation of noradrenaline but not of dopamine from l‐DOPA.
The increase in flexor reflex activity induced by the noradrenaline receptor stimulating agent clonidine was not changed by FLA‐63, indicating that the noradrenaline receptor sensitivity was not influenced.
After depletion of the noradrenaline stores, the small formation of noradrenaline from l‐DOPA may be of greater functional significance for the noradrenaline receptor stimulation than the greater formation of dopamine, but the dopamine formed also has a slight action. With intact noradrenaline stores, displacement of endogenous noradrenaline by newly formed dopamine contributes, at least after monoamine oxidase inhibition, to the increase in the flexor reflex activity caused by l‐DOPA.
Lack of relationship between myocardial cyclic AMP concentrations and inotropic effects of sympathomimetic amines
Authors: BENFEY B. G. 
Published: July 2012

Summary
Sympathomimetic amines which increase the contractility of the isolated heart were tested for effects on cyclic AMP concentrations in rabbit heart slices and on adenyl cyclase activity in rabbit heart homogenate.
Noradrenaline, as expected, stimulated adenyl cyclase activity and increased cyclic AMP concentrations, but dopamine and phenylephrine were ineffective.
This result does not support the concept that cyclic AMP plays an essential role in the inotropic effect of sympathomimetic amines.
Preferential secretion of adrenaline or noradrenaline by the cat adrenal in vivo in response to different stimuli
Authors: FEUERSTEIN GIORA , GUTMAN YEHUDA 
Published: July 2012

Summary
The concentrations of adrenaline and noradrenaline in the adrenal vein and the adrenal gland of the cat were studied in response to different stimuli leading to increased catecholamine (CA) secretion.
Haemorrhage and hypoglycaemia, but not acute exposure to cold or intravenous administration of cocaine, induced considerable increases in total catecholamine secretion.
The ratio of the concentration of adrenaline to noradrenaline in adrenal vein plasma during the control period was higher than the ratio in the adrenal gland itself.
Haemorrhage increased noradrenaline secretion considerably more than adrenaline secretion so that the ratio of the concentration of adrenaline to noradrenaline in adrenal vein plasma was significantly lower than in the adrenal gland itself.
Hypoglycaemia induced by insulin increased catecholamine secretion, with the adrenaline to noradrenaline ratio significantly higher than in the adrenal gland itself.
Hypothermia resulted in a fall of the initial high ratio of adrenaline to noradrenaline, to a value similar to that in the adrenal gland.
Neither cocaine nor changes in adrenal plasma flow affected the adrenaline to noradrenaline ratio in adrenal vein blood.
It is concluded that preferential release from the adrenal gland of either adrenaline or noradrenaline is possible in vivo in response to different stimuli.
Modification by choline of adrenergic transmission in rat mesenteric arteries
Authors: MALIK K. U. , McGIFF J. C. 
Published: July 2012

Summary
The action of choline on the vasoconstrictor responses of the perfused mesenteric arteries of the rat to sympathetic nerve stimulation and to injected noradrenaline has been investigated.
The infusion of choline (500 μg/ml), for periods of 15 s, increased the response to sympathetic nerve stimulation, whereas the infusion of the same concentration for 20 min greatly reduced the response to nerve stimulation. Choline (up to 500 μg/ml), infused either for short or long periods, did not alter the response to injected noradrenaline.
The inhibitory action of choline on the response to nerve stimulation was abolished either by an increase in the calcium concentration from 1·8 to 5·4 mm or by simultaneous infusion of (+)‐amphetamine or atropine.
The results suggest that choline in concentrations of 500 μg/ml has the same effect on adrenergic transmission in mesenteric arteries as acetylcholine at concentrations of 5 ng/ml.
Differences in the uptake, storage and metabolism of (+)‐ and (—)‐noradrenaline
Authors: IVERSEN L. L. , JARROTT B. , SIMMONDS M. A. 
Published: July 2012

Summary
The rate of uptake of (+)‐ and (—)‐noradrenaline was measured in isolated perfused hearts of reserpine treated rats, mice and guinea‐pigs by fluorimetric analysis of the removal of catecholamine from the perfusion medium. In rat and mouse heart (—)‐noradrenaline was taken up significantly more rapidly than (+)‐noradrenaline, but no stereochemical specificity was found for noradrenaline uptake in guinea‐pig hearts.
Using radioactively labelled (+)‐14C‐noradrenaline and (—)‐3H‐noradrenaline, the kinetic constants for uptake into noradrenaline‐containing and dopamine‐containing synaptosomes from rat brain were determined. The uptake by noradrenaline terminals in the hypothalamus had a higher affinity for (—)‐noradrenaline than for the (+)‐isomer, but no differences in affinity were found for uptake into dopamine terminals.
When equal amounts of labelled (+)‐ and (—)‐noradrenaline were injected in vivo in double isotope experiments, the (+)‐isomer disappeared more rapidly than the (—)‐isomer from rat heart and spleen, but no significant differences were found between the rates of disappearance of the two isomers from rat brain or in the whole mouse.
Analysis of the radioactive metabolites of the two isomers of noradrenaline after administration of mixed doses of the labelled substances showed that a significantly higher proportion of (+)‐noradrenaline was metabolized to normetanephrine than of (—)‐noradrenaline, in the whole mouse, rat heart and rat brain.
The effects of dipyridamole on coronary post‐occlusion hyperaemia and on myocardial vasodilatation induced by systemic hypoxia
Authors: PARRATT J. R. , WADSWORTH R. M. 
Published: July 2012

Summary
. The arterial pO2 of anaesthetized cats was reduced to 33 mmHg by supplying a mixture of oxygen and nitrogen as the respiratory gas. This produced vasodilatation in the myocardial bed which was not increased after the injection of dipyridamole (1 mg/kg).
. Reactive hyperaemia was observed following occlusion of the left anterior descending coronary artery for 10–120 seconds. The duration of the period of reactive hyperaemia was increased after the injection of dipyridamole. This effect of dipyridamole was most pronounced when the longest periods of occlusion were used.
. These results support the hypothesis that myocardial reactive hyperaemia is at least partly caused by adenosine released from hypoxic myocardial cells. The vasodilatation occurring during systemic hypoxia, on the other hand, is probably mediated via a different mechanism.
The effect of bradykinin on denervated tongue
Authors: RADMANOVIĆ B. , TORRES SONIA H. 
Published: July 2012

Summary. The contractile response of the chronically denervated tongue of the cat to chorda stimulation, and to close arterial injections of bradykinin, acetylcholine (ACh) and other drugs was examined.. Bradykinin in doses of 50 ng‐20 μg injected close arterially always produced a contractile response of the denervated tongue. Sodium nitrite (1 mg i.a.) and isoprenaline (3–200 ng i.a.) also produced contracture; histamine (40–100 ng i.a.) evoked an increase in tension in only 2 out of 5 experiments.. Tubocurarine in doses of 0·25–1 mg injected intra‐arterially, produced a large and long‐lasting contracture of the denervated tongue. When the contracture was over, the effect of bradykinin was reduced to about half; the effects of ACh and chordo‐lingual nerve stimulation were markedly reduced (over 80%), and those of sodium nitrite and isoprenaline were transiently abolished. Gallamine only slightly reduced the effect of bradykinin.. Close intra‐arterial injection of physostigmine (100 μg) potentiated the effect of ACh and chordo‐lingual nerve stimulation, but did not increase the response to bradykinin.. Cocaine (1 mg/kg i.v.) deeply depressed the response to bradykinin, and moderately reduced the responses to ACh (41%) and to chorda stimulation (66%).. In 2 out of 7 experiments, close arterial injections of bradykinin (100–500 ng) to the denervated tibialis anterior muscle of the cat, produced a contractile response. Bradykinin in small doses (200–250 ng) injected immediately before ACh potentiated its effect. On the other hand, the effect of ACh was depressed when given immediately after a big dose of bradykinin (10–15 μg).. The possible mechanism of action of bradykinin and other substances on denervated muscle is discussed.
Actions of the selective inhibitor of cholinesterase tetramonoisopropyl pyrophosphortetramide on the rat phrenic nerve‐diaphragm preparation
Authors: HEFFRON P. F. 
Published: July 2012

Summary
. Tetramonoisopropyl pyrophosphortetramide (iso‐OMPA) added for 15 min to the rat isolated phrenic nerve‐diaphragm in a concentration of 30 μm, produced a complete selective and stable inhibition of cholinesterase. A concentration of 3 μm produced near complete inhibition of cholinesterase, and a concentration of 300 μm also inhibited acetylcholinesterase marginally.
. Inhibition of cholinesterase was associated with a sustained increase in the neuromuscular blocking action of exogenous butyrylcholine but not of exogenous acetylcholine. Iso‐OMPA, 300 μm, in addition caused transient increases in the sensitivity of the rat diaphragm to exogenous acetylcholine and butyrylcholine. In the same concentration, it had a curare‐like action on the frog rectus abdominis muscle preparation.
. Iso‐OMPA, 30 μm, caused reversible increases in the amplitude of the twitch response and tetanic responses, which were of a similar magnitude in the indirectly stimulated preparation and the directly stimulated curarized preparation. Caffeine had a similar effect on the twitch response and its effectiveness was increased by iso‐OMPA, and vice‐versa. Amongst anticholinesterases, octamethyl pyrophosphortetramide and tetraethylpyrophosphate also enhanced the amplitude of the tetanic response, but paraoxon, dyflos, and mipafox did not.
. It is concluded that iso‐OMPA, in concentrations (3 and 30 μm) which in 15 min give near maximal or maximal selective inhibition of cholinesterase, has no effect on the transmission of nerve impulses at the neuromuscular junction, but enhances reversibly the amplitude of the contractile response to stimulation by a direct action upon the muscle fibre, which involves a mechanism related to but not identical with that by which caffeine potentiates twitch tension. In higher concentrations, iso‐OMPA has a curare‐like action at the neuromuscular junction.
Effects of clozapine on cerebral catecholaminergic neurone systems
Authors: BARTHOLINI G. , HAEFELY W. , JALFRE M. , KELLER H. H. , PLETSCHER A. 
Published: July 2012

Summary
. Clozapine, a dibenzodiazepine derivative claimed to possess antipsychotic properties in man without producing extrapyramidal disorders, greatly increased the turnover of cerebral dopamine in the rat.
. The drug itself was virtually devoid of cataleptigenic activity in rats; however, it antagonized prochlorperazine‐induced catalepsy.
. It is proposed that clozapine causes a blockade of striatal dopamine receptors which is of the surmountable type in contrast to that produced by cataleptigenic neuroleptics. In addition, clozapine may also increase the turnover of cerebral noradrenaline.
Responses of the isolated, perfused human spleen to sympathetic nerve stimulation, catecholamines and polypeptides
Authors: AYERS A. B. , DAVIES B. N. , WITHRINGTON P. G. 
Published: July 2012

Summary
The responses of the smooth muscle of the capsule and blood vessels of the isolated, perfused human spleen to sympathetic nerve stimulation, adrenaline, noradrenaline, angiotensin, oxytocin, vasopressin, isoprenaline and acetylcholine have been investigated and compared with those of dog spleen.
Stimulation of the postganglionic sympathetic nerves to the human spleen at frequencies of 3–10 Hz evoked graded vasoconstriction but very small changes in spleen volume.
The injection of adrenaline and noradrenaline in doses of 0·25–25 μg to the human spleen produced graded increases in splenic vascular resistance with very small decreases in spleen volume.
Administration of the α‐adrenoceptor blocking drug phenoxybenzamine completely abolished or considerably reduced the vascular responses of the human spleen to sympathetic nerve stimulation or the injection of noradrenaline.
The vascular action of adrenaline was often reversed to elicit a vasodilatation after phenoxybenzamine suggesting the presence of β‐adrenoceptors in the vascular bed. This was confirmed by the administration of isoprenaline which induced a marked reduction in vascular resistance of the human spleen.
The polypeptides angiotensin and vasopressin induced a marked vasoconstriction in the human spleen without changes in the spleen volume. These effects were uninfluenced by the administration of phenoxybenzamine.
The polypeptide oxytocin caused a slight vasodilatation in the human spleen, an effect almost exactly mimicked by the preservative chlorobutanol.
Preliminary experiments suggest that noradrenaline is the transmitter released by the postganglionic nerves to the human spleen.
These results provide direct evidence that the normal human spleen, unlike that of the dog, does not have a reservoir function. It is suggested that contractions of the enlarged human spleen may occur in various pathological conditions.
Fluorometric estimation of 4‐hydroxy‐3‐methoxyphenylethyleneglycol sulphate in brain
Authors: MEEK JAMES L. , NEFF NORTON H. 
Published: July 2012

Summary
A simple, sensitive, and selective method was developed for the fluorimetric estimation of 4‐hydroxy‐3‐methoxyphenylethyleneglycol sulphate (MOPEG‐SO4) in rat brain.
MOPEG‐SO4 was isolated on a DEAE Sephadex column. Fluorescence was measured at 465 nm (excitation at 320 nm) after heating the column eluate with acid and reheating after adding ethylene diamine.
The concentration in brain of MOPEG‐SO4 increased after blockade of its transport from brain by treatment with probenecid and decreased after inhibiting its synthesis by treatment with α‐methyltyrosine or pargyline.
Our studies suggest that measurement in changes in the rate of formation of MOPEG‐SO4 may be a useful index of noradrenaline turnover.
Pharmacology of AH 5158; a drug which blocks both α‐ and β‐adrenoceptors
Authors: FARMER J. B. , KENNEDY I. , LEVY G. P. , MARSHALL R. J. 
Published: July 2012

Summary
AH 5158 differs from conventional adrenoceptor blocking drugs in producing competitive blockade of both α‐ and β‐adrenoceptors.
AH 5158 is 5–18 times less potent than propranolol in blocking β‐adrenoceptors. It resembles propranolol in its non‐selective blockade of β1‐cardiac and β2‐vascular and tracheal adrenoceptors and in its lack of intrinsic sympathomimetic activity.
AH 5158 is 2–7 times less potent than phentolamine in blocking α‐adrenoceptors. AH 5158 itself is more active on β‐ than α‐adrenoceptors.
Blockade of noradrenaline vasopressor responses by AH 5158 in anaesthetized dogs was dose‐dependent up to 1 mg/kg but no further blockade was obtained with larger doses of AH 5158. ‘Self‐limiting’ blockade was not observed in dogs pretreated with cocaine, or in untreated dogs if the vasopressor agent was oxymetazoline instead of noradrenaline. A possible cause of ‘self‐limiting’ blockade is discussed.
In doses higher than those required for either α‐ or β‐adrenoceptor blockade, AH 5158 produced effects on cardiac muscle that are attributable to membrane‐stabilizing activity. This was manifested as a negative inotropic action in spinal dogs and in guinea‐pig left atrial strips, as a negative chronotropic action in syrosingopine pre‐treated dogs, and as an increase in the effective refractory period of guinea‐pig left atrial strips. AH 5158 was 3–11 times less potent than propranolol in these tests.
In open chest dogs AH 5158 resembled propranolol in reducing cardiac output, rate and contractility, effects which are attributable to β‐adrenoceptor blockade. The drug differed from propranolol in decreasing rather than increasing total peripheral resistance and in causing larger decreases in arterial blood pressure at equipotent β‐adrenoceptor blocking doses. These differences are attributable to the α‐adrenoceptor blocking actions of AH 5158.
In anaesthetized dogs, intravenously administered AH 5158 antagonized both catecholamine and ouabain‐induced arrhythmias. Orally administered AH 5158 lowered systolic arterial pressure in conscious renal hypertensive dogs.
These results show AH 5158 to possess a novel profile of activity. Possible uses of the drug in cardiovascular disorders such as hypertension, angina pectoris and cardiac arrhythmias are discussed.
The effect of certain β‐adrenoceptor antagonists on overdrive suppression
Authors: KELLIHER G. , LUOTO JOANNE , ROBERTS J. 
Published: July 2012

Summary
Propranolol, as the racemate and the (+)‐ and (–)‐isomers (400 μg/l.) and practolol (50 mg/l.) were tested for their effects on atrial and ventricular rates and on the duration of overdrive suppression (ODI) in isolated perfused cat hearts with surgically‐induced heart block.
Racemic propranolol and the (+)‐ and (–)‐isomers prolonged ODI and slowed the rate of the ventricular pacemaker; the (+)‐ and (–)‐isomers also reduced the rate of the atrial pacemaker. Practolol shortened ODI and increased the rate of the atrial and ventricular pacemakers.
The (+)‐ and (–)‐isomers were more potent than the racemate; the (–)‐isomer was more potent than the (+)‐isomer. The results suggest there is a stereospecific mechanism involved in the biological distribution of propranolol.
Twenty‐four hours after reserpine treatment (5 mg/kg, i.p.) practolol continued to increase the rate of the atrial and ventricular pacemakers but did not shorten ODI.
The mechanism by which these agents affect myocardial excitability and automaticity is discussed.
Further studies on nitrofurantoin excretion in dog hepatic bile
Authors: CONKLIN J. D. , SOBERS R. J. , WAGNER D. L. 
Published: July 2012

Summary
. Results obtained with a dog donor‐recipient model indicate that following intravenous administration of nitrofurantoin sodium, nitrofurantoin is subjected to enterohepatic cycling. At least one‐third of the nitrofurantoin originally excreted in the donors' bile after a nitrofurantoin dose of 3 mg/kg is reabsorbed intestinally in the recipients within 3 hours.
. After intraduodenal administration of a nitrofurantoin suspension to dogs at doses ranging from 2 to 12 mg/kg, about 10% of the dose is recovered in bile as nitrofurantoin within 6 hours. A hydrocholeretic effect was also observed which correlated with the amount of drug administered. Both biliary drug excretion and the related hydrocholeresis appeared linearly related over the drug dose range.
. The hydrocholeresis observed in dogs within 3 h after intravenously administered nitrofurantoin sodium, equivalent to 3 mg/kg nitrofurantoin, was at least ten times that seen following the intravenous administration of an equimolar dose of dehydrocholic acid given as its sodium salt.
Alterations in the activities of ornithine and histidine decarboxylases provoked by testosterone in mice
Authors: GRAHN B. , HENNINGSSON S. S. G. , KAHLSON G. , ROSENGREN ELSA 
Published: July 2012

Summary
The urinary excretion of putrescine has been determined in female mice before and during repeated injections of testosterone.
Testosterone administration effected a striking increase in the excretion of free putrescine.
Ornithine decarboxylase (l‐ornithine carboxy‐lyase; E.C. 4.1.1.17) and histidine decarboxylase (l‐histidine carboxy‐lyase; E.C. 4.1.1.22) activities of mouse kidney and liver were examined. In the kidney, following testosterone administration, ornithine decarboxylase activity was found to be substantially elevated, whereas that of histidine decarboxylase was depressed. In the liver, by contrast, the activity levels of these enzymes were not significantly altered by testosterone treatment.
The possibility of a functional interrelation between putrescine and histamine, via the two enzyme activities investigated, is discussed.
Anaphylaxis in the guinea‐pig isolated heart: selective inhibition by burimamide of the positive inotropic and chronotropic effects of released histamine
Authors: CAPURRO NORINE , LEVI R. 
Published: July 2012

Summary
Anaphylaxis was induced in the isolated heart of the guinea‐pig in the presence of burimamide at concentrations of 4 × 10−5M and 2·7 × 10−4M.
Burimamide did not affect the immunological release of histamine; however, it selectively antagonized the positive inotropic and chronotropic effects of released histamine. The antagonism of the positive chronotropic effect was concentration‐dependent.
Neither the negative dromotropic effect nor the decrease in coronary flow rate occurring during anaphylaxis were inhibited by burimamide.
The results are in agreement with the double histamine receptor theory and suggest that, in the heart of the guinea‐pig, H2‐receptors are involved in the positive inotropic and chronotropic effects of released histamine, and H1‐receptors in the negative dromotropic effect.
The determination of dopamine by a modification of the dihydroxyindole fluorimetric assay
Authors: ATACK C. V. 
Published: July 2012

Summary
A simplified sensitive fluorimetric assay for dopamine based on the hydroxyindole principle is described. Oxidation of dopamine by ferricyanide and subsequent tautomerization both occur in the same, strongly alkaline, ethanolic solution in the presence of metabisulphite. The reaction is self‐regulating, and since times of additions of reagents are relatively unimportant and the final fluorescence is very stable, a large number of samples can be assayed together.
The method was developed for assaying dopamine in n‐ethanolic (50%)–HCl eluates, after purification on a strongly acidic cation exchange column as previously described (Atack & Magnusson, 1970). Portions, up to 1 ml volume, of the 3·5 ml eluate can be taken. No preliminary, time‐consuming, neutralization step is required before oxidation. Fluorescence intensity shows a linear relation with concentration for 1–5,000 ng of dopamine per 1·6 ml of final solution, both in pure solutions and in column eluates.
Fluorescence readings from biological material are given, with evidence for their reproducibility. These, together with other data, demonstrate the relative accuracy of the ‘tissue blank’ and indicate that amounts of dopamine greater than 3 ng per column can confidently be detected, and amounts greater than 10 ng can be measured quantitatively.
Fluorescence spectra are presented for the fluorophore derived from authentic dopamine, and from suspected dopamine extracted from spinal cord of normal rats and rats treated with reserpine plus an inhibitor of synthesis. Values for the concentration of dopamine of 20 and <3 ng/g, respectively, were obtained.