bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of phenoxybenzamine on the uptake and metabolism of noradrenaline in the rat heart and vas deferens
Authors: IVERSEN L. L. , LANGER S. Z.
Published: July 2012

. In the isolated rat heart perfused with various concentrations of (±)‐3H‐noradrenaline (3H‐NA) the addition of phenoxybenzamine, cocaine or desipramine to the perfusion medium resulted in an inhibition of 3H‐NA uptake which appeared on kinetic analysis to be of a competitive nature.

. Phenoxybenzamine also blocked the formation of labelled metabolites of 3H‐NA in the heart at all perfusion concentrations of 3H‐NA; this effect appeared to be unrelated to the inhibition of the neuronal uptake of NA produced by phenoxybenzamine, since no blockade of 3H‐NA metabolism was produced by cocaine in similar experiments.

. In slices of rat vas deferens incubated with various concentrations of 3H‐NA, cocaine and desipramine and phenoxybenzamine were also shown to act as competitive inhibitors of NA uptake. Cocaine and phenoxybenzamine were less potent inhibitors of uptake in the vas deferens than they were in the heart; desipramine was equally potent in both tissues.

. When vas deferens slices were incubated in a medium containing phenoxybenzamine for 30 min before the addition of 3H‐NA, the resulting inhibition of 3H‐NA uptake was increased and changed to a non‐competitive type of interaction.

. In hearts or vasa deferentia taken from animals pretreated in vivo with phenoxybenzamine (20 mg/kg), a significant inhibition of 3H‐NA uptake was found when the tissues were exposed to low concentrations of 3H‐NA but not when higher concentrations of 3H‐NA were used.
Sodium‐dependent accumulation of 5‐hydroxytryptamine by rat blood platelets
Authors: SNEDDON J. M.
Published: July 2012

. The influence of sodium and potassium on the accumulation of 5‐hydroxytryptamine (5‐HT) by rat blood platelets was investigated.

. An absolute dependence of 5‐HT uptake on the sodium concentration in the medium was found.

. Removal of potassium reduced the uptake by about 60% High concentrations of potassium inhibited sodium‐dependent accumulation.

. The observations have been discussed in terms of a carrier‐mediated transport process for 5‐HT operating in the platelet membrane.
A hyoscine‐resistant contraction of isolated chicken oesophagus in response to stimulation of parasympathetic nerves
Authors: HASSAN T.
Published: July 2012

. Contractions of the chicken isolated oesophagus or separated external muscle produced by stimulation of the vagus and descending oesophageal nerves were abolished by hyoscine (1–100 μg/ml.) if the duration of stimulation was less than 5 sec, but prolonged stimulation produced delayed contractions not antagonized by hyoscine.

. The contractions to nerve stimulation were abolished by nerve section but not by bretylium, hexamethonium or tubocurarine.

. In decerebrate chickens, intravenous hyoscine abolished the contractions of the oesophagus produced by nerve stimulation, but previous intravenous injection of hyoscine into chicks did not prevent subsequently isolated oesophageal preparations from contracting to nerve stimulation.

. Prolonged nerve stimulation of an isolated oesophageal preparation did not produce a contraction from a piece of isolated guinea‐pig ileum or post‐crop chick oesophagus suspended in the same organ‐bath.

. It seems possible that small amounts of a slow contracting substance were released from the stimulated nerves together with acetylcholine.
Aspects of the pharmacology of a new anthelmintic: pyrantel
Authors: AUBRY M. L. , COWELL PAULINE , DAVEY M. J. , SHEVDE S.
Published: July 2012

. The pharmacological properties of an anthelmintic, pyrantel, and some of its analogues have been described and compared with piperazine in a variety of vertebrate and helminth preparations.

. Pyrantel and its analogues in common with nicotine and decamethonium cause spastic paralysis in chicks and contracture of the chick semispinalis and toad rectus abdominis muscles.

. In the soleus and anterior tibialis muscles of the cat, pyrantel in large amounts caused a short‐lived neuromuscular block that was preceded by initial depolarization.

. In preparations from cat and rat, pyrantel showed properties common to both competitive and depolarizing neuromuscular blocking drugs.

. Pyrantel blocked the contracture evoked by transmural stimulation and caused a marked contracture of the worm. Piperazine caused a gradually developing reduction in the responses to transmural stimulation and no contracture.

. Pyrantel and its analogues caused a slowly developing contracture of strip preparations of Ascaris, being more than 100 times more active than acetylcholine in this respect. Piperazine caused a relaxation of Ascaris strip preparations and in common with (+)‐tubocurarine blocked the responses to acetylcholine and pyrantel analogues on this preparation.

. Pyrantel caused depolarization and increased spike discharge frequency in single muscle cells of Ascaris, these changes being accompanied by increase in tension. Piperazine, on the other hand, caused hyperpolarization and reduction in spike discharge frequency and relaxation, and antagonized the effects of pyrantel.
Inhibition of rabbit intestine mediated by α‐ and β‐adrenoceptors
Authors: BOWMAN W. C. , HALL MOIRA T.
Published: July 2012

. The effects of some α‐ and β‐adrenoceptor agonists and antagonists were studied on isolated segments of rabbit intestine in an attempt to characterize the two types of inhibitory response produced by sympathomimetic amines.

. Phenylephrine, an α‐adrenoceptor agonist, produced an inhibition of rapid onset, from which recovery occurred despite the continued presence of the drug. On washout there was an overshoot in contraction height. Isoprenaline, a β‐adrenoceptor agonist, produced an inhibition of slow onset which was maintained throughout the presence of the drug and there was no overshoot on washout.

. Adrenaline resembled phenylephrine more closely than it resembled isoprenaline, in that it showed more affinity for α‐adrenoceptors, whereas noradrenaline, and the transmitter released on periarterial nerve stimulation, behaved more like isoprenaline, although both types of receptor were affected.

. Adenosine‐5′‐triphosphate produced an inhibition resembling that produced by an α‐adrenoceptor agonist, whereas the dibutyryl analogue of cyclic adenosine 3′,5′‐monophosphate (cyclic 3′,5′‐AMP) produced an inhibition resembling that produced by a β‐adrenoceptor agonist.

. In critical concentrations theophylline augmented and imidazole inhibited β‐adrenoceptor mediated responses, as well as responses to dibutyryl cyclic AMP. However, additional actions of theophylline and imidazole were also demonstrated.

. Responses mediated by α‐adrenoceptors, but not those mediated by β‐adrenoceptors, were blocked by membrane stabilizers, quinidine being the most potent of those studied.

. The results are discussed in relation to the possible mechanisms of action of α‐ and β‐adrenoceptor agonists.
Some factors influencing the release of 5‐hydroxyindol‐3‐ylacetic acid in the forebrain
Authors: PADJEN A. , RANDIĆ MIRJANA
Published: July 2012

. Electrical stimulation of the mid‐brain raphé in anaesthetized adrenalectomized rats produced a significant decrease in the forebrain content of 5‐hydroxytryptamine (5‐HT) and an increase in the concentration of 5‐hydroxyindol‐3‐ylacetic acid (5‐HIAA).

. Stimulation of peripheral sensory nerves did not influence either the forebrain content of 5‐HIAA or the efflux of 5‐HIAA from the cerebral cortex.

. Probenecid (200 mg/kg) caused a twofold increase in 5‐HIAA content of the rat's forebrain, while the efflux of 5‐HIAA from the cerebral cortex remained unchanged.

. Stimulation of the mid‐brain raphé in animals pretreated with probenecid does not produce the rise in the forebrain levels of 5‐HIAA seen in stimulated untreated controls and does not affect the efflux of 5‐HIAA from the cerebral cortex.

. In preliminary experiments, lysergic acid diethylamide (LSD 25) substantially reduced and/or prevented the increase in the release of 5‐HIAA in the forebrain observed in untreated animals with raphé stimulation.
The action of angiotensin on the human colon in vitro
Authors: FISHLOCK D. J. , GUNN A.
Published: July 2012

. The action of angiotensin on the circular and longitudinal muscle of the human colon has been studied in vitro. The ED50 value (g/ml) of circular muscle was 8.7 × 10−8 and of longitudinal muscle 3.1 × 10−8, while the corresponding figures for acetylcholine were 1.6 × 10−6 and 1.1 × 10−6, respectively. Angiotensin caused a sustained contraction associated with prolonged tachyphylaxis.

. As the action of angiotensin was not antagonized by atropine, hexamethonium or procaine, angiotensin appeared to act directly on the smooth muscle of the human colon.

. Lidoflazine is not a specific antagonist of angiotensin.
Influence of thyroid hormones on the sensitivity of cardiac and smooth muscle to biogenic amines and other drugs
Authors: COVILLE P. F. , TELFORD J. M.
Published: July 2012

. Rats and guinea‐pigs were injected with 1‐thyroxine or thyroidectomized. Sensitivity of isolated tissues and of the intact cardiovascular system to drugs was investigated.

. Thyroxine increased the sensitivity of the isolated perfused heart to noradrenaline, adrenaline, isoprenaline, acetylcholine and histamine.

. Thyroxine increased the sensitivity of the rat isolated uterus to noradrenaline, adrenaline, isoprenaline, acetylcholine, histamine and 5‐hydroxytryptamine.

. In contrast, thyroxine decreased the sensitivity of the isolated ileum to acetylcholine, histamine and 5‐hydroxytryptamine, but not to adrenaline.

. Thyroxine also decreased the sensitivity of the isolated aorta to noradrenaline, adrenaline, histamine and 5‐hydroxytryptamine.

. In pithed rats, thyroxine potentiated pressor responses to (+)‐amphetamine but not to noradrenaline or synephrine.

. In anaesthetized thyroxine‐treated rats, blood pressure responses to (+)‐amphetamine were potentiated while those to noradrenaline were unaltered. Responses to acetylcholine were increased, and the response to isoprenaline became purely pressor.

. Thyroxine‐induced changes in the sensitivity of the isolated uterus and ileum to modification of the concentration of calcium in the physiological salt solution paralleled the changes in drug sensitivity of these tissues.

. In general, thyroidectomy produced the opposite effects to those of thyroxine.

. It is concluded that there is no specific interaction between thyroxine and sympathomimetic amines, the effect of thyroxine on drug sensitivity being non‐specific.
Changes in sodium pool and kinetics of sodium transport in frog skin produced by amiloride
Authors: SALAKO L. A. , SMITH A. J.
Published: July 2012

. Amiloride produces a decrease in size of the active sodium transport pool of isolated frog skin.

. Rate coefficients for sodium movement into and out of the transporting cells across the outside membrane are decreased by amiloride. The rate coefficient for sodium extrusion across the inside membrane is not significantly affected.

. In the presence and in the absence of amiloride, the relation of sodium transport to outside sodium concentration exhibits similar saturation kinetics but amiloride reduces sodium transport rate at every sodium concentration of the outside solution.

. Labelling of skin with 14C‐amiloride from the outside solution is significantly greater than labelling with 14C‐inulin.

. The results of these studies suggest that amiloride reacts with sites on the outside membrane of the transporting cells as a result of which the rate of sodium movement across this membrane is diminished.
Prejunctional actions of some β‐adrenoceptor antagonists in the vas deferens preparation of the guinea‐pig
Authors: MYLECHARANE E. J. , RAPER C.
Published: July 2012

. The β‐adrenoceptor antagonists propranolol, pronethalol, MJ 1999 and Ciba 39089‐Ba reduced responses to field stimulation of the guinea‐pig isolated vas deferens preparation without significantly affecting responses to exogenously added noradrenaline.

. This prejunctional blocking action of the drugs cannot be correlated with their action as β‐adrenoceptor antagonists or non‐specific depressants.

. The blockade produced was more pronounced at low (520 Hz) than at high (50 Hz) frequencies of stimulation.

. The blockade was slow in onset, and once established was poorly reversed by washing the preparation over a period of 1 to 2 h.

. The blockade produced could be reversed by dexamphetamine and cocaine.

. These experiments suggest that the β‐adrenoceptor antagonists may have some actions which closely resemble those of the adrenergic neurone blocking agent guanethidine.
A method for the estimation of the catecholamines and their metabolites in brain tissue
Authors: CRAWFORD T. B. B. , YATES CELIA M.
Published: July 2012

A method is described whereby the catecholamines, their precursors and metabolites may be estimated in the same brain sample. The method, outlined below, was rigorously tested in pure solution before being applied to the estimation of the catechol and methoxyamines in extracts of rat brain. (i) The brain tissue was homogenized in perchloric acid and the perchloric acid removed as its insoluble potassium salt. (ii) The acid metabolites of the amines were extracted from the acidified extract into ethyl acetate. (iii) After extraction with ethyl acetate, the aqueous extract was treated with acetic anhydride and sodium hydrogen carbonate and the acetylated derivatives of the amines extracted into dichloromethane. (iv) The aqueous solution remaining after extraction with dichloromethane contains the acetylated amino‐acids. Acetyl‐dopa could be extracted into dichloromethane only after acidification of this aqueous solution. The acetyl‐dopa in this dichloromethane extract could be estimated fluorimetrically. (v) The dichloromethane extract containing the acetylated amines was chromatographed on paper in the organic phase of a mixture of toluene: ethyl acetate: methanol: water, 10: 1: 5: 5. (vi) The acetylated amines were eluted and estimated fluorimetrically. A new method was developed for the estimation of 3‐methoxytyramine and its acetylated derivative.

The reproducibility of the method was demonstrated by the consistent estimates obtained for the concentrations of noradrenaline, dopamine and 3‐methoxytyramine in whole rat brain. Adrenaline and metanephrine were not detected. The concentration of normetanephrine in rat brain was at the limit of detection of the method.

Although the estimation for the levels of endogenous amines in whole rat brain were consistent, the recoveries of exogenous amines taken through the procedure were low and very variable. Control experiments demonstrated that the exogenous amines were lost at the perchloric acid extraction stage of the procedure.
Cholinergic mechanisms on the heart and coronary circulation
Authors: BLESA MARTA I. , ROSS G.
Published: July 2012

The effects of rapid intracoronary injection of acetylcholine (ACh) were studied in anaesthetized open chest dogs. Changes in phasic coronary blood flow were followed with non‐cannulating electromagnetic flow probes and in contractile force with isometric strain gauges.

Increasing doses of ACh from 0.01 to 100 μg produced progressively larger increases in systolic and diastolic coronary blood flow and progressive decreases in end‐diastolic vascular resistance which were blocked by atropine but not by propranolol.

Contractile force showed both negative and positive responses. The negative inotropic effect was small and was blocked by atropine but not by propranolol. The threshold for the negative inotropic response was higher than for the coronary vasodilator effect and the dose response curve was flatter. The positive inotropic response usually showed two components. One component reached its maximum 13 to 18 s after injection, had a high threshold (over 1 μg), was potentiated by atropine and blocked by propranolol. The other reached its maximum 25 to 60 s after the injection, had a threshold between 0.01 and 0.1 μg, and was blocked by atropine but not by propranolol.

These results suggest that the coronary dilator response, the negative inotropic response and part of the positive inotropic response are mediated through “muscarinic” receptors. The remaining component of the positive inotropic response appears to involve catecholamine release.
Effects of monoamine oxidase inhibitors and amphetamine on hypothermia produced by halothane
Authors: FELDBERG W. , LANG W. J.
Published: July 2012

In cats, the effects of tranylcypromine and pheniprazine, two monoamine oxidase (MAO) inhibitors with strong amphetamine‐like actions, of pargyline, an inhibitor without amphetamine‐like actions, and of amphetamine itself, were examined on the hypothermia produced by a 2 hr period of halothane inhalation.

The hypothermia was prevented by intraperitoneal injections of the three MAO inhibitors. Tranylcypromine and pheniprazine acted in doses of a few milligrams, pargyline in doses of over 100 mg.

The hypothermia was prevented by injections into the cerebral ventricles of tranylcypromine and pheniprazine, in doses which were effective also on intraperitoneal injection; intraperitoneal injections were sometimes more effective. The large doses of pargyline needed to prevent the hypothermia when injected intraperitoneally were not tested by the intraventricular route, as the injections had to be made in a volume of 0.1 ml. In smaller doses intraventricular pargyline was not effective.

The hypothermia was prevented by an intraperitoneal or intraventricular injection of amphetamine in a dose as little as 1 mg; intraperitoneal injections were sometimes more effective.

The effects of tranylcypromine and pargyline given intraperitoneally, and of amphetamine given intraventricularly as well, were also examined on the hypothermia produced by an intraventricular injection of 200 μg noradrenaline. The two MAO inhibitors and amphetamine prevented the hypothermia, or greatly reduced it.

It is concluded (a) that even on intraventricular injection the MAO inhibitors must first be absorbed into the blood stream before they can prevent the hypothermia of a halothane anaesthesia; (b) that their action may not be solely on the anterior hypothalamus; and (c) that they may not act only through MAO inhibition.
Some pharmacodynamic properties of carrageenin in the rat
Authors: DI ROSA M. , SORRENTINO L.
Published: July 2012

Carrageenin oedema is suppressed by pre‐treating the rats with cellulose sulphate, a kininogen depleting agent. This inhibition is closely related to the dose of cellulose sulphate and to the time course of kininogen depletion.

Oedema induced by egg white or by dextran, in which the mediators are histamine and 5‐hydroxytryptamine, is quite unaffected by cellulose sulphate treatment.

Carrageenin injected intravenously lowers the arterial blood pressure of rats. This hypotensive effect is unaffected by histamine antagonists and is abolished by protease inhibitors and thus seems to be due to kinin release from plasma substrates.

Like cellulose sulphate, carrageenin enhances the esterolytic activity of the blood from treated rats when incubated with benzoyl‐arginine ethyl ester.

The ability of carrageenin to activate the kinin‐forming system could account for both its inflammatory and hypotensive effects.
The mechanism of the paralysing action of tetramisole on Ascaris somatic muscle
Authors: ACEVES J. , ERLIJ D. , MARTÍNEZ‐MARAÑÓN R.
Published: July 2012

. Tetramisole (100 μg/ml) paralysed live Ascaris in 3 min.

. Tetramisole (10 μg/ml) caused a sustained contraction of the isolated somatic muscles of the worm. This contraction was not blocked by curare nor by piperazine.

. Tetramisole reduced the resting potential of Ascaris muscle from 34 ± 4 to 10 ± 1 mV.

. Tetramisole caused contraction of Ascaris muscle previously depolarized with high K+ solutions. This observation suggests that tetramisole can induce a contracture that is independent of membrane depolarization.
A comparison between the blocking actions of 2‐(4‐phenylpiperidino) cyclohexanol (AH 5183) and its N‐methyl quaternary analogue (AH 5954)
Authors: MARSHALL I. G.
Published: July 2012

. The neuromuscular blocking activities of AH 5183 (2‐(4‐phenylpiperidino) cyclohexanol) and its N‐methyl quaternary analogue (AH 5954) were compared in rapidly stimulated nerve‐skeletal muscle preparations of the rat, chicken and cat.

. The evidence indicated that in isolated preparations the neuromuscular block produced by both AH 5183 and AH 5954 was primarily pre‐junctional in origin. That produced by AH 5954 was readily reversible either by washing the tissue or by reducing the stimulation frequency, whereas that produced by AH 5183 was difficult to reverse in these ways.

. Low doses of AH 5954 sensitized the rat hemidiaphragm preparation to the neuromuscular blocking action of choline. The neuromuscular block produced by choline was reversible by tetraethylammonium but not by neostigmine. This suggested that the blocking action of choline is at least partly pre‐junctional in nature.

. In anaesthetized cats AH 5954 possessed a biphasic neuromuscular blocking action. The initial phase was rapid in onset, suggestive of a postjunctional action, whereas the second phase was prolonged and reversible by choline, suggestive of a prejunctional inhibitory action on the choline transport mechanism. AH 5183 produced no initial blocking action and was irreversible by choline.

. Both AH 5183 and AH 5954 possessed local anaesthetic and α‐adrenoceptor blocking actions. These actions and the neuromuscular blocking action were affected to different degrees by quaternization, suggesting that the three main actions of the two drugs are independent.

. It was concluded that AH 5954 and AH 5183 act at different pre‐junctional sites at the neuromuscular junction, AH 5954 acting extraneuronally by inhibiting choline transport and AH 5183 intraneuronally at the level of the synaptic vesicle membrane.
A comparison of the antinociceptive actions of cholinomimetic and morphine‐like drugs
Authors: IRESON J. D.
Published: July 2012

. The antinociceptive activity of morphine, nalorphine, oxotremorine and eserine has been examined in mice in electroshock and phenylbenzoquinone writhing tests.

. The effectiveness of these drugs alone, in combination with each other, and in combination with the muscarinic antagonist atropine sulphate, and with the narcotic antagonist naloxone has also been investigated.

. In both tests morphine was effective and antagonized by naloxone.

. Nalorphine was active in the phenylbenzoquinone test but only slightly active in the electroshock test: it was antagonized by naloxone in both tests.

. Morphine was potentiated by nalorphine in the phenylbenzoquinone test. but antagonized by it in the electroshock test.

. Oxotremorine was effective in both tests, and was antagonized by atropine sulphate.

. Eserine was active only in the phenylbenzoquinone test, and was antagonized by atropine sulphate.

. Oxotremorine was potentiated by eserine in the phenylbenzoquinone test. but antagonized by it in the electroshock test.

. Crossed agonist and partial agonist experiments produced enhancement.

. No antagonism was seen in the crossed antagonist experiments.

. The similarities between the effects of the two classes of drugs are discussed, and the conclusion drawn that they act by separate mechanisms.
Central effects of 6‐hydroxydopamine on the body temperature of the rat
Authors: SIMMONDS M. A. , URETSKY N. J.
Published: July 2012

. Rats which had been pretreated with intraventricular injections of 6‐hydroxydopamine (6‐OHDA) to cause a selective depletion of brain noradrenaline (NA) to 20.7% of control brain NA and brain dopamine (DA) to 34.6% of control brain DA retained an unimpaired ability to regulate their body temperatures on exposure to heat or cold. This is discussed in relation to the possible role of brain NA in the central control of body temperature.

. Intraventricular injections of 6‐OHDA in normal rats at room temperature caused an acute, dose dependent hypothermia of up to 4.5° C which lasted for 4–5 hours. Depletion of brain NA and DA by prior treatment with 6‐OHDA markedly reduced the hypothermic response to a subsequent dose of 6‐OHDA. Selective depletion of brain NA without affecting brain DA did not reduce the response to 6‐OHDA. The acute hypothermic response to 6‐OHDA, may therefore, be related to a release of DA in the brain.
Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non‐adrenergic inhibitory nerves in the gut
Authors: BURNSTOCK G. , CAMPBELL G. , SATCHELL D. , SMYTHE ANNE
Published: July 2012

. Stimulation of the vagal non‐adrenergic inhibitory innervation caused the release of adenosine and inosine into vascular perfusates from the stomachs of guinea‐pigs and toads.

. Stimulation of portions of Auerbach's plexus isolated from turkey gizzard caused the release of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP).

. ATP, added to solutions perfused through the toad stomach vasculature, was broken down to adenosine, inosine and adenine.

. Of a series of purine and pyrimidine derivatives tested for inhibitory activity on the guinea‐pig isolated taenia coli, ATP and ADP were the most potent.

. ATP caused inhibition of twelve other gut preparations previously shown to contain non‐adrenergic inhibitory nerves. The inhibitory action of ATP was not prevented by tetrodotoxin.

. Quinidine antagonized relaxations of the guinea‐pig taenia coli caused by catecholamines or adrenergic nerve stimulation. Higher concentrations of quinidine antagonized relaxations caused by ATP or non‐adrenergic inhibitory nerve stimulation.

. When tachyphylaxis to ATP had been produced in the rabbit ileum, there was a consistent depression of the responses to non‐adrenergic inhibitory nerve stimulation but not of responses to adrenergic nerve stimulation.

. It is suggested that ATP or a related nucleotide is the transmitter substance released by the non‐adrenergic inhibitory innervation of the gut.
Cardiovascular actions of substituted adenosine analogues
Authors: ANGUS J. A. , COBBIN L. B. , EINSTEIN ROSEMARIE , MAGUIRE M. H.
Published: July 2012

The effects of adenosine on systemic blood pressure, coronary blood flow and cardiac contractility and rate were studied in anaesthetized open‐thorax dogs.

The potency and duration of action of substituted adenosine analogues were compared with that of adenosine.

With the exception of 2‐chloroadenosine, in which coronary dilator activity was enhanced, substitution in the 2‐position of the adenosine molecule reduced activity.

In all cases 2‐substitution prolonged the duration of the coronary dilator activity of adenosine.

N6‐Methylation of adenosine and 2‐chloroadenosine reduced their coronary dilator activities, but had no effect on the duration of the response.

Comparison of the coronary dilator potencies and hypotensive activities of 2‐ethylaminoadenosine and 2‐methoxyadenosine indicates that these analogues have some specificity for the coronary bed.
Effects of ranatensin, a polypeptide from frog skin, on isolated smooth muscle
Authors: CLINESCHMIDT B. V. , GELLER R. G. , GOVIER W. C. , PISANO J. J. , TANIMURA T.
Published: July 2012

The actions of bretylium tosylate on neuromuscular transmission in the rat phrenic nerve diaphragm preparation have been investigated by electro‐

On the guinea‐pig ileum, threshold doses elicit repeated maximal spike contractions which are blocked by atropine. In the presence of atropine, higher concentrations of ranatensin elicit small contraction spikes superimposed on a relatively weak sustained contraction. These latter two actions are not blocked by increasing the concentration of atropine.

Other smooth muscle preparations respond as follows: rat uterus, rhythmic contractions; rat duodenum, relaxation; rabbit aortic strip, contraction. Atropine has no effect on the above responses. The rat aortic strip does not respond to ranatensin. Ranatensin is four times as active as bradykinin on the rat uterus.

Ranatensin can be readily distinguished from other known peptides such as angiotensin, bradykinin and the eledoisin‐like peptides, by bioassay.
Comparative study of antral gastrin activity in some mammals
Authors: AMURE B. O. , OMOLE A.
Published: July 2012

The amounts of crude gastrin extract and the gastrin activities of extracts from antral mucosa of several mammalian species have been determined.

The yield of crude gastrin powder per gramme wet weight of antral mucosa was greater in goats and rabbits than in cat, dog, man or pig.

Statistical differences do not appear to exist between the potencies of gastrin from the various species. The potencies of the powders were within the ranges 1·2–1·8 μg porcine gastrin II/mg with the exception of the extract from frozen dog antra (0·8 μg/mg).

During prolonged freezing of animal antra and consequent thawing before extraction, significant losses in gastrin activity occurred in the dog.

The amounts of gastrin activity per gramme wet weight of antral mucosa from herbivores (goat, rabbit and cattle) were greater than those from non‐herbivores (cat, dog, man and pig).
Responses of mean arterial pressure to pressor agents and diuretics in renal hypertensive and salt hypertensive rats
Authors: NICHOLAS T. E.
Published: July 2012

The responses of the mean arterial pressure to (—)‐noradrenaline, tyramine, angiotensin II‐val5‐amide, vasopressin and rat renin have been contrasted in renal hypertensive and in salt plus desoxycorticosterone hypertensive rats. The responses were measured in rats both unanaesthetized and rats anaesthetized with pentobarbitone.

Responses of unanaesthetized, ganglion blocked renal hypertensive rats to noradrenaline, tyramine and vasopressin markedly exceeded, and to angiotensin II and renin were markedly smaller than, those of unanaesthetized ganglion blocked salt + DOC hypertensive animals. Responses to angiotensin and to renin were apparently enhanced in the latter animals.

Hydrochlorothiazide and frusemide markedly reduced mean arterial pressure in salt + DOC hypertensive rats before and after ganglionic blockade.

Neither diuretic caused significant reduction in the mean arterial pressures of unanaesthetized, renal hypertensive rats in the absence of ganglionic blockade: frusemide did so in anaesthetized and unanaesthetized rats after ganglionic blockade.

Whereas the diuretics did not affect the responses of the renal hypertensive rats to pressor agents, frusemide and to a lesser extent hydrochlorothiazide tended to depress the responses to pressor agents in salt induced hypertension.

Hydrochlorothiazide did not influence mean arterial pressure in unanaesthetized rats with neurogenic hypertension.
Evidence for inhibition of the reuptake of 5‐hydroxytryptamine and noradrenaline by tetrahydronaphthylamine in rat brain
Authors: BRUINVELS J.
Published: July 2012

The concentrations of 5‐hydroxytryptamine (5‐HT), 5‐hydroxyindolacetic acid (5‐HIAA) and noradrenaline (NA) in homogenized rat brains were determined after intraperitoneal injection of 1,2,3,4‐tetrahydro‐2‐naphthylamine (THN).

THN caused a decrease in the concentration of brain 5‐HIAA without altering its 5‐HT content, but the percentage of ‘free 5‐HT’ in the supernatant increased. The decrease in 5‐HIAA and the increase in free 5‐HT were negatively correlated, suggesting inhibition of the reuptake of 5‐HT.

THN decreased brain NA content without changing free NA. The fact that no increase in free NA occurred is ascribed to the action of catechol‐O‐methyl‐transferase.

Inhibition of the reuptake of NA and of 5‐HT was further studied by using the compounds 5‐methyl‐α‐ethyl‐meta‐tyramine (H 75/12) and 4,α‐dimethyl‐meta‐tyramine (H 77/77). The results of these studies also suggested inhibition by THN of the reuptake of 5‐HT as well as of NA.

The action of THN is explained by inhibition of the reuptake of NA and of 5‐HT and by release of NA from its stores. However, the possibility is not excluded that, instead of releasing NA from its stores, THN inhibits the enzyme dopamine‐β‐hydroxylase.
Comparison of the effects of morphine, pethidine and pentazocine in rabbits pretreated with a monoamine oxidase inhibitor
Authors: PENN R. G. , ROGERS K. J.
Published: July 2012

Rabbits were premedicated with pargyline and the changes in rectal temperature measured after the intravenous infusion of morphine, pentazocine and pethidine.

Pethidine produced pronounced rises in rectal temperature which were dose dependent. One out of the four rabbits given 1 mg/kg died in hyperthermia. Four out of the four rabbits given 5 mg/kg died in hyperthermia. Doses of 10 mg/kg of pethidine caused no significant change in the rectal temperature of rabbits not pretreated with pargyline.

Morphine and pentazocine in doses of 1 mg and 10 mg/kg did not significantly alter the rectal temperature of rabbits pretreated with pargyline except for one rabbit which developed a delayed hyperthermia following the injection of morphine 1 mg/kg.
Pharmacokinetic model for the successive demethylation and biliary secretion of methyl orange in the rat
Authors: O'REILLY W. J. , PITT PATRICIA A. , RYAN A. J.
Published: July 2012

A one‐compartment pharmacokinetic model was developed in which a drug underwent two successive metabolical reactions (for example, metabolism followed by conjugation) and free drug and both metabolites were excreted.

Techniques were described whereby graphical estimates of the first‐order rate constants may be derived from cumulative excretion data on the drug and its metabolites. Computer simulation techniques were used to show that the experimental data permit reasonably accurate estimation of the rate constants of the model by graphical and computer methods.

Tritiated methyl orange (2 mg) was administered to five groups of six rats with biliary cannulation. The bile produced by each animal was collected at hourly intervals for 6 h and the amounts of methyl orange and its metabolites, 4′sulpho‐4‐methylaminoazobenzene and 4′sulpho‐4‐aminoazobenzene, determined by thin layer chromatography and radioactive counting techniques.

The data were analysed graphically and with an iterative digital computer programme to yield the first‐order rate constants for the successive demethylation steps in the metabolism of methyl orange. The removal of the first methyl group had a rate constant of 0·684 ± 0·142 h−1 (± s.d.) and the second methyl group 1·00 ± 0·302 h−1. The rate constant for biliary excretion of the free methyl orange was 0·164 ± 0·042 h−1, for the monomethyl derivative 0·672 ± 0·461 h−1 and for the demethylated metabolite 6·413 ± 3.222 h−1.
Bretylium potentiation of the contractor responses of isolated rabbit aortic strips to potassium and tyramine
Authors: KURAHASHI K. , SHIBATA S.
Published: July 2012

Pretreatment of rabbit aortic strips with bretylium potentiated the contractor response to potassium and tyramine but not to noradrenaline. On the other hand, such pretreatment inhibited the response to nicotine.

Even in reserpinized or cold stored aortic strips, pretreatment with bretylium enhanced the contractor response to potassium and tyramine.

Pretreatment of fresh, reserpinized, or cold stored aortic strips with pheniprazine potentiated the contractor response to potassium and tyramine.

Pretreatment of aortic strips with bretylium or pheniprazine did not potentiate the response to 5‐hydroxytryptamine (5‐HT).

The results indicate that both bretylium and pheniprazine potentiate the action of tyramine and potassium, not by presynaptic mechanisms, but by postsynaptic action, causing an increase in the sensitivity of the effector cells to the stimulants.
Effect of prolonged treatment with tetracosactrin on hypothalamo‐pituitary‐adrenal function in the rat
Authors: HODGES J. R. , MITCHLEY SUSAN
Published: July 2012

The functional integrity of the hypothalamo‐pituitary adrenal (HPA) system was assessed in rats after prolonged treatment with tetracosactrin.

Adrenal size and sensitivity to corticotrophin were increased.

Both the circadian rhythm and the stress‐induced increase in HPA activity were inhibited. The circadian rhythm recovered before the response to stress.

Tetracosactrin given after betamethasone treatment delayed the return of a normal HPA response to stress.

Suppression of HPA activity appeared to be the result of a direct action of tetracosactrin and not entirely due to the elevations in the plasma corticosterone concentration which it caused.
Daunorubicin metabolism: estimation of daunorubicin reductase
Authors: BACHUR N. R. , HUFFMAN D. H.
Published: July 2012

Daunorubicin reductase, an enzyme ubiquitous in all mammalian tissues tested, converts daunorubicin, a cancer chemotherapeutic antibiotic, to daunorubicinol. A method for the estimation of daunorubicinol and daunorubicin reductase is described.

Daunorubicin and daunorubicinol were quantitatively extracted from enzyme assay mixtures with 0·3 n HCl in 50% ethanol and then completely hydrolysed to their respective aglycones. The aglycones were extracted, concentrated into toluene, separated by silicic acid microcolumn chromatography, and estimated by spectrofluorimetry.

Compared to previous methods, this method is highly reproducible and sensitive.
Relationship between internal Na+/K+ and the accumulation of 14C‐5‐hydroxytryptamine by rat platelets
Authors: SNEDDON J. M.
Published: July 2012

5‐Hydroxytryptamine (5‐HT) transport has been investigated in rat blood platelets poisoned with dinitrophenol‐sodium fluoride or ouabain.

The inhibition of transport produced by different concentrations of the metabolic inhibitors has been correlated with changes in the internal Na+ and K+ concentrations of the platelets.

Platelets poisoned in a high K+ medium maintained a high internal K+ concentration in the absence of cellular metabolism. When transferred to Krebs solutions containing different concentrations of Na+ they accumulated 5‐HT by a process that was related to the magnitudes of the internal and external Na+ concentrations.

The results are consistent with the hypothesis that the spontaneous movement of ions through the platelet membrane is capable of providing, at least in part, the energy requirements for 5‐HT transport.
Effect of iontophoretic application of cholinergic agonists and their antagonists to guinea‐pig pelvic ganglia
Authors: HOLMAN MOLLIE E. , MUIR T. C. , SZURSZEWSKI J. H. , YONEMURA K.
Published: July 2012

The electrical activity of guinea‐pig pelvic ganglion cells following iontophoretically applied cholinergic drugs, alone and during orthodromic nerve stimulation via the hypogastric nerve, has been recorded intracellularly.

Iontophoretic application of nicotine (Nic) and acetylcholine (ACh) reduced membrane resistance and caused a depolarization which in approximately 80% of cells led to the firing of action potentials. In the remainder, depolarization was unaccompanied by firing.

Iontophoretic application of Nic and ACh reduced or abolished the amplitude of successively evoked orthodromic responses.

ACh‐induced depolarization, unlike that caused by tetanic stimulation, was not followed by a subsequent increase in the frequency of synaptic potentials.

Di‐hydroβerythroidine (DHβE) and atropine (Atr) inhibited the response to both orthodromic stimulation and iontophoretic application of Nic and ACh.

There was no evidence for the existence of muscarinic receptors in guinea‐pig pelvic ganglia. Iontophoretic application of muscarinic agonists alone and after tetanic stimulation of the hypogastric nerve produced no significant depolarization of the ganglion cell membrane.
Cutaneous reactions to intradermal prostaglandins
Authors: CRUNKHORN PEARL , WILLIS A. L.
Published: July 2012

The effects of intradermally injected prostaglandins (PGs) E1, E2, F1α and F2α have been examined in the rat and in man.

PGE1 and PGE2 caused an increase in local vascular permeability in rat skin; their potency was comparable with that of other putative mediators of inflammation (histamine, bradykinin, and 5 ‐hydroxytryptamine), but PGF1α and PGF2α were only slightly active even at a dose of 1 μg.

Prior administration of mepyramine and methysergide, or depletion of skin mast cell amines with compound 48/80, indicated that PGE2 exerted its permeability effect in the rat by a release of mast cell amines.

Nanogramme doses of PGE1 and PGE2 or microgramme doses of PGF1α and PGF2α injected intradermally into the human forearm induced weal and flare responses.

It is concluded that prostaglandins E1 and E2 can act as intermediates in the production of hyperaemia and oedema resulting from cell damage in the rat and man.
Action of fenfluramine on monoamine stores of rat tissues
Authors: COSTA E. , GROPPETTI A. , REVUELTA A.
Published: July 2012

Fenfluramine is an anorexogenic agent used clinically because it is devoid of central stimulatory effects.

In rats, fenfluramine causes a depletion of 5‐hydroxytryptamine (5‐HT) from the telencephalon + diencephalon which lasts longer than one might have expected from the biological half life of fenfluramine. The depleting effects of fenfluramine do not extend to brainstem, stomach and heart stores of 5‐HT.

Fenfluramine causes an increase in the turnover rate of tel‐diencephalic 5‐HT but such an acceleration could not be detected in the 5‐HT stores of the brainstem.

It is inferred that the effects of fenfluramine on brain 5‐hydroxytryptamine may be related to the accumulation of a fenfluramine metabolite in 5‐HT neurones.

High doses of fenfluramine cause a depletion of catecholamine stores in brain and heart but the time course of this depletion is shorter than the depletion of brain 5‐HT.
Effects of Na+ and K+ on the uptake of metaraminol by rabbit ventricular slices
Authors: PATON D. M.
Published: July 2012

The ionic dependence of [3H]‐metaraminol transport by rabbit ventricular slices was studied.

Transport was Na+ dependent. Choline, Li+, K+, Rb+ or Cs+ could not be substituted for Na+.

Transport was K+ dependent. Rb+ and Cs+, but not Li, could be substituted for K+, their relative potencies being K+=or >Rb+>Cs+>Li+. Higher concentrations of K+, Rb+, Cs+ and Li inhibited [3H]‐metaraminol transport.

The inhibitory effects on transport of either a marked reduction in the concentration of Na+ or of omission of K+ were rapidly reversible on exposure of slices to Krebs solution.

The inhibitory effect of ouabain on [3H]‐metaraminol transport was markedly time dependent, being significantly increased by preincubation with ouabain. The inhibitory action of ouabain was not affected, however, by the Na+ concentration present during preincubation.

An inwardly directed Na+ gradient did not increase [3H]‐metaraminol transport in slices in which Na+ pumping had been prevented by 10−5m ouabain, 4° C, omission of K+ or by metabolic inhibition.

These findings provide additional evidence that the Na+ and K+ activated adenosine triphosphatase may participate in the transport of metaraminol and related amines. In the absence of Na+ pumping, induced Na+ gradients were unable to produce transport of amine as would be predicted by the co‐transport model proposed by Bogdanski & Brodie (1969).
Effects of morphine on choline acetyltransferase levels in the caudate nucleus of the rat
Authors: DATTA K. , THAL L. , WAJDA I. J.
Published: July 2012

Choline acetyltransferase (choline‐o‐acetyltransferase 2.3.1.6.) concentrations were determined in the caudate nucleus, thalamus, and cortex of control and morphine treated rats. The enzyme was assayed using a modified radiochemical method on a number of selected days, one hour after the last injection of 30 mg/kg of morphine and also during the subsequent phase of abstinence from morphine.

Significant lowering of choline acetyltransferase activity in the caudate nucleus area was found in two cases, one hour after the first dose of morphine and upon subsequent abstinence from morphine.

The enzyme activity in the two other parts of the brain remained at the normal levels.

The presence of endogenous inhibitors formed during morphine administration was excluded.

The relationship of a possible effect of morphine on the tissue binding of the enzyme and the subsequent lowering of its activity was tested by homogenization of the caudate nucleus area in different media. The decrease in enzyme activity occurred in all extraction media one hour after morphine administration.

Inhibitory effects of in vitro addition of morphine to caudate nucleus homogenate, obtained from normal and morphine treated rats, were found to occur only at very high concentrations of the drug, negating the possibility of direct inhibitory effects of morphine.

These experiments suggest two possible causes of the observed effects, which can be responsible for the lowering of enzyme activity, and can be operative simultaneously: (1) a negative feedback mechanism of accumulated acetylcholine, occurring after the first dose of morphine, and (2) the possible changes in enzyme configuration produced by morphine treatment.
Effect of β‐adrenoceptive blocking agents on the response to bronchoconstrictor drugs in the guinea‐pig air overflow preparation
Authors: BURDEN D. T. , PARKES M. W. , GARDINER D. G.
Published: July 2012

Propranolol augmented the bronchoconstrictor response to methacholine or histamine, recorded by air overflow in the anaesthetized, vagotomized guinea‐pig.

After adrenalectomy, propranolol was still active, though less so than before.

In the pithed guinea‐pig, there was no augmentation of the effect of bronchoconstrictors on air overflow. The action of propranolol could thus be due to the β‐adrenoceptor blockade of compensatory sympathetic bronchodilator activity, as concluded by McCulloch, Proctor & Rand (1967).

Electrical stimulation of the thoracic region of the spinal cord of the pithed guinea‐pig reduced the effect of bronchoconstrictors on air overflow. This reduction could be blocked by propranolol; practolol was much less effective.
Studies on the inhibition of clearance of organic dyes by Saramycetin
Authors: COONEY D. A. , DAVIS R. D. , HOMAN E. R. , RAKIETEN N. , SCHAEPPI U. , VANATTA G.
Published: July 2012

Saramycetin, a polypeptide antifungal antibiotic has been found to retard the clearance of sulphobromophthalein (BSP) in man. An explanation for this observation was sought in several lower species.

Doses of Saramycetin without effect on the other standard tests of hepatic function or on hepatic morphology profoundly altered the disposition of BSP and several other dyes in mice and dogs.

Saramycetin strongly inhibited the hepatic enzyme which conjugates BSP to reduced glutathione, provoked a regurgitation of BSP from the liver into the bloodstream, and was anticholeretic in the dog.

These diverse actions of Saramycetin may, in concert, explain the altered clearance of BSP. It is suggested that low doses of Saramycetin exert a pharmacological effect on certain hepatic excretory processes, whereas high doses are toxic.
The effect of lithium salts on the urinary excretion of α‐oxoglutarate in man
Authors: BOND P. A. , JENNER F. A. , LEE C. R. , LENTON ELIZABETH , POLLITT R. J. , SAMPSON GWYNETH A.
Published: July 2012

. Lithium ions in therapeutic doses cause an increase in the renal excretion of α‐oxoglutarate and glutaric acid.

. The excretion is probably due to reduced renal tubular reabsorption.

. Neither citrate, lactate nor pyruvate excretion rises.
The occurrence of tolerance to a central depressant effect of nicotine
Authors: MORRISON CATHLEEN F. , STEPHENSON JANE A.
Published: July 2012

. Rats were injected with 0·8 mg nicotine/kg, 0·8 mg amphetamine/kg or with saline immediately before being tested for 30 min in activity boxes.

. During the first 3 trials the nicotine group were less active than the controls but from trial 5 onwards nicotine had a stimulant effect. The stimulant effect of the amphetamine did not alter with repeated injection.