bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
The influence of suxamethonium on cardiovascular and respiratory function in the anaesthetized horse
Authors: LEES P. , TAVERNOR W. D.
Published: July 2012

In horses anaesthetized with halothane the intravenous administration of suxamethonium chloride, at a dose level of 0.2 mg/kg, produced a short‐lived period of hypoventilation, which was associated with increases in arterial blood Pco2 levels and in plasma concentrations of bicarbonate, sodium and potassium ions, and reductions in arterial blood pH and Po2 values.

The respiratory depressant action of suxamethonium chloride 0.2 mg/kg was accompanied by increases in blood pressure and heart rate. Doses of suxamethonium chloride 0.4 mg/kg produced similar but quantitatively greater changes in cardiovascular and respiratory function. These effects were not accompanied by cardiac arrhythmias, with the exception of one animal, in which an unusually prolonged period of apnoea occurred.

The cardiovascular effects of suxamethonium during halothane anaesthesia were diminished but not abolished when the respiratory depressant action of suxamethonium was prevented by applying positive pressure ventilation.

The cardiovascular effects of suxamethonium in horses anaesthetized with halothane were partially antagonized by propranolol and completely antagonized by hexamethonium. It is suggested that the cardiovascular effects of suxamethonium are mediated by two distinct mechanisms: reflexly mediated increases in heart rate and sympathetic vasoconstrictor tone due to the respiratory depression, and a direct stimulant action of suxamethonium on peripheral, autonomic ganglia.

Much less pronounced changes in cardiovascular function, but not in respiratory function, were recorded when suxamethonium was administered to horses anaesthetized with ether.

A slight degree of tachyphylaxis to the cardiovascular and respiratory effects of suxamethonium was recorded in horses anaesthetized with halothane.

Some atypical effects of suxamethonium on respiration are described.
Inhibition of the carotid sinus reflex by the chronic administration of propranolol
Authors: DUNLOP D. , SHANKS R. G.
Published: July 2012

The changes in heart rate and arterial pressure produced by the intravenous injection of isoprenaline (0.5 μg/kg), noradrenaline (1.0 μg/kg), phenylethylamine (0.5 mg/kg), amphetamine (0.5 mg/kg) and by bilateral occlusion of the carotid arteries and by stimulation of the central ends of both vagus nerves have been recorded in groups of dogs anaesthetized with pentobarbitone.

The acute intravenous injection of propranolol (1 mg/kg) reduced the increases in heart rate produced by the six procedures, the increases in arterial pressure in response to the last five procedures and the decrease in pressure produced by isoprenaline.

This decrease produced by propranolol in the pressor responses resulted from a reduction in the increases in cardiac output elicited by the five procedures and has been attributed to blockade of cardiac adrenergic β‐receptors.

Three groups of dogs were pretreated for 6 weeks by the oral administration of either placebo, propranolol 50 mg/kg daily or propranolol 10 mg/kg twice daily. The responses to the six test procedures were obtained 17–24 hr after the last dose of propranolol, when only minimal blockade of adrenergic β‐receptors was present. In the propranolol‐treated groups, the pressor response to carotid occlusion but not to the other test procedures was significantly reduced.

The pressor response to carotid occlusion was not reduced in a fourth group of dogs given a single dose of propranolol (50 mg/kg) 24 hr before the test procedures.

The mechanism of this selective reduction in the pressor response to occlusion of the carotid arteries is not clear. It is suggested that it may contribute to the hypotensive action of propranolol in man during prolonged oral administration.
The role of Uptake2 in the extraneuronal metabolism of catecholamines in the isolated rat heart
Authors: LIGHTMAN S. L. , IVERSEN L. L.
Published: July 2012

. (±)‐3H‐NA and labelled metabolites of NA were estimated in rat hearts after perfusion with various concentrations of NA in the range 0·01–50·0 μg/ml. Labelled metabolites of NA accounted for only a small proportion of the total uptake of radioactivity at low perfusion concentrations, but accounted for 50% of the total uptake at 1 μg NA/ml., thereafter declining to progressively smaller proportions at higher perfusion concentrations.

. If the formation of labelled metabolites of 3H‐NA was blocked by a combination of monoamine oxidase and catechol‐O‐methyl transferase inhibitors, the accumulation of unchanged 3H‐NA was doubled when hearts were perfused with 1 μg NA/ml.

. In hearts perfused with 0·5 μg NA/ml., an accumulation of unchanged 3H‐NA was demonstrated in the presence of a combination of metabolic inhibitors and metaraminol. This appeared to be due to Uptake2, since the accumulation of NA under these conditions could be prevented by a low concentration of normetanephrine.

. Phenoxybenzamine prevented extraneuronal uptake (Uptake2) and metabolism of 3H‐NA with an estimated ID50 of 2·5 μm. The inhibition of Uptake2 by phenoxybenzamine (2·0 μm) was diminished at very high NA concentrations, suggesting that the drug may act competitively with NA.

. It was concluded that Uptake2 operates at all catecholamine concentrations in the rat heart, but that in the lower range (less than 2·5 μg/ml. for NA and less than 0·75 μg/ml. for adrenaline) any catecholamine taken up by this process is rapidly metabolized. Thus the accumulation of unchanged amine is seen only at high perfusion concentrations.

. The relevance of these results to an understanding of the possible physiological and pharmacological importance of Uptake2 is discussed.
Carbon tetrachloride metabolism in the rabbit
Authors: FOWLER J. S. L.
Published: July 2012

. Carbon tetrachloride was administered by stomach tube to rabbits and its distribution in fat, liver, kidney and muscle studied by gas liquid chromatography, during the next 48 hr.

. Chloroform, hexachloroethane and two unidentified chlorinated metabolites were detected in the tissues.

. Hexachloroethane may arise by dimerization of free trichloromethyl radicals.
Cephalexin: human studies of absorption and excretion of a new cephalosporin antibiotic
Authors: GOWER P. E. , DASH C. H.
Published: July 2012

. Serum levels, half‐lives and urine concentrations of cephalexin, an oral cephalosporin antibiotic which is unique in its absorption and excretion, are reported in human volunteers, fasting, non‐fasting and non‐fasting plus probenecid. Accumulation does not seem to occur.

. Cephalexin clearance was 376 ml./min and the ratio of cephalexin/creatinine clearances was 2·6 in one volunteer.

. Cephalexin had no effect on the urinary excretion of leucocytes, red cells or protein.

. The very high rate of absorption giving high serum levels and urine concentrations suggest cephalexin will be a useful antibiotic in susceptible bacterial infections in man.
The relevance of β‐receptor blockade to ouabain‐induced cardiac arrhythmias
Authors: DOHADWALLA A. N. , FREEDBERG A. S. , WILLIAMS E. M. VAUGHAN
Published: July 2012

. (+)‐propranolol and (±)‐propranolol are comparable in their potency as a local anaesthetic on the intact and desheathed frog sciatic nerve.

. (±)‐propranolol is much more potent than (+)‐propranolol as a β‐receptor blocking agent and also more effective than the latter in protecting guinea‐pigs against ouabain‐induced ventricular fibrillation.

. In isolated rabbit atria (–)‐, (+)‐ and (±)‐propranolol, and I.C.I. 50172, which has hardly any local anaesthetic activity, greatly reduce the rate of rise of the intracellularly recorded action potential at concentrations which have no significant effect on electrical threshold, contractions, spontaneous frequency, maximum driving frequency, repolarization time or conduction velocity.
The distribution of 3H‐labelled cardenolides between isolated guinea‐pig atrial tissue and circulating, oxygenated whole blood
Authors: LÜLLMANN H. , PETERS T. , van ZWIETEN P. A.
Published: July 2012

. An experimental method was developed that allowed the incubation of isolated organs in circulating whole blood. The circulating blood was oxygenated with a specially designed dise‐oxygenator and drawn through the system by means of a roller pump.

. The method proved suitable for guinea‐pig isolated atria, rabbit duodenum and to a lesser extent for chronically denervated rat diaphragm. Isolated atria could be kept for several hours. Various parameters of the circulating blood (haemolysis, pH, O2 saturation, concentration of electrolytes) remained satisfactory for at least 5 hr. The method proved convenient for pharmacological and kinetic studies on isolated organs, suspended in whole blood of the corresponding species. The organs showed normal spontaneous mechanical activity and also responded to electrical stimuli and various drugs.

. The uptake of 3H‐labelled ouabain, digoxin, digitoxin and digitoxigenin was studied in guinea‐pig isolated atria, suspended in circulating blood. The uptake reached equilibrium after 60–90 min. With respect to the total serum radioactivity the “apparent” tissue/medium (T/M) ratios obtained for the four drugs were within the range 0.4–1.1. If, however, the amount of free, non protein bound drug was taken as a base for the calculations, the following “true” T/M ratios were obtained: 3H‐ouabain 0.45; 3H‐digoxin 1.6; digitoxin 8.8; digitoxigenin 8.4. These values are virtually the same as those obtained with atria, suspended in an aqueous medium. Obviously, the uptake of 3H‐cardenolides from whole blood is determined by the amount of free non‐proteinbound drug.

. 3H‐digitoxin and 3H‐digitoxigenin were taken up by guinea‐pig erythrocytes to a small extent. No measurable amounts of 3H‐ouabain and 3H‐digoxin were taken up by erythrocytes.
Muscarinic component of splanchnic‐adrenal transmission in the dog
Authors: KAYAALP S. O. , McISAAC R. J.
Published: July 2012

. The effect of atropine on catecholamine release evoked by stimulation of the splanchnic nerve was studied in the adrenal medulla of the dog. The magnitude of the catecholamine release was estimated biologically on the basis of the pressor response occurring in the perfused and acutely sympathectomized hindquarters of the same dog by comparing it with responses elicited by intravenous injection of adrenaline.

. Atropine reduced the responses to nerve stimulation, and appeared to have a more prominent effect on the responses elicited by stimulation at moderate frequency (10 pulses/sec).

. Hexamethonium or nicotine caused a more powerful, but not complete, blockade of transmission; the subsequent injection of atropine caused a further inhibition of the residual responses, leading to a complete, or near complete, abolition of the release by nerve stimulation.

. The data were taken as evidence that transmission of impulses through muscarinic receptors occurs in normal conditions in the adrenal medulla of the dog, though this type of transmission is less prominent than that through nicotinic receptors.
Effects of calcium, sodium and potassium ions on contractility of isolated atria and their responses to noradrenaline
Authors: TODA N.
Published: July 2012

. Rabbit left atrial preparations driven electrically at different rates were used for studies on inotropic effects of cations, drugs and coupled pacing. Sino‐atrial node‐atrial preparations were used for investigating the chronotropic effect of noradrenaline.

. The contractile tension‐driving rate relationship was moved upwards by an elevation of [Ca++]o, coupled pacing and noradrenaline. In preparations exposed to Na+‐poor and K+‐free solutions the contractile strength at low driving rates (6 to 30 c/min) was markedly enhanced, but at high rates (120 to 240 c/min) it was not influenced. The contractile strength was reduced at low [Ca++]o and at high [K+]o.

. The positive inotropic effect of noradrenaline was markedly inhibited by a reduction of [Ca++]o and to some extent by a reduction of [K+]o. The noradrenaline‐inotropy was not appreciably affected by an elevation of [Ca++]o and a reduction of [Na+]o.

. Cardiac excitability studied in preparations driven at high rates was enhanced by noradrenaline, a reduction of [K+]o and an elevation of [Ca++]o, but was reduced at low [Ca++]o, low [Na+]o and high [K+]o.

. The positive chronotropic response to noradrenaline was enhanced at high [Ca++]o, low [Na+]o and low [K+]o, but was reduced in solutions deficient in Ca++ or rich in K+.

. Inotropic effects of the ions and of coupled pacing were compared with those of ouabain. It is suggested that characteristic changes in the tension‐rate curve seen in Na+‐poor, K+‐free and ouabain‐containing solutions are correlated with an inhibition of active processes in the cardiac cell membrane, which affect ionic movements across it. It seems likely that mechanisms mediating adrenergic responses of the contractile tissue and the S‐A node are associated with [Ca++]o.
Preliminary investigations of a new beta‐adrenoceptive receptor blocking drug, LB46, in man
Authors: HILL R. C. , TURNER P.
Published: July 2012

. Preliminary studies in man of a new beta‐adrenoceptive receptor blocking drug, dl‐4‐(2‐hydroxy‐3‐isopropylaminopropoxy)‐indole (LB46), are described.

. LB46, 0.5 mg by oral administration, appeared to be of similar potency to propranolol 20 mg in inhibiting isoprenaline‐induced and exercise‐induced tachycardia.

. In comparable beta‐receptor blocking doses LB46 did not show the negative chronotropic property possessed by propranolol.
The actions of ethinyloestradiol on the pituitary‐adrenal system of the rat
Authors: FLACK J. D.
Published: July 2012

. Single doses of ethinyloestradiol stimulate the pituitary adrenal axis of the female rat during quiescent conditions.

. After a stimulus which releases endogenous ACTH, there is an inhibition of the release of corticosterone from the adrenal gland, but an increase in the corticosterone stored in the gland.

. Ethinyloestradiol (1·0 mg/kg) injected acutely or daily for 7 days does not affect the corticosterone binding capacity of plasma in female rats, or the clearance rate of an injection of corticosterone.

. Prolonged treatment with ethinyloestradiol and ACTH inhibits the pituitary‐adrenal response to a stress and to an ACTH injection, indicating a block at the adrenal and pituitary level.

. The adrenal gland recovers more rapidly than the pituitary after cessation of the oestrogen treatment.

. The inhibition of the pituitary‐adrenal response to stress after oestrogen is probably caused by inhibition of cholesterol synthesis as suggested by others. Oestrogens can increase corticoid secretion during non‐stress conditions, however, so precursor lack through exhaustion cannot be excluded.

. It is suggested that the inhibition of the stress response after prolonged ACTH treatment is due to a decrease in sensitivity of the adrenal cortex after frequent ACTH stimulation, but the possibility that it is due to a reduction in circulating cholesterol cannot be ruled out.
Pharmacological significance of biogenic amines in the lungs: noradrenaline and dopamine
Authors: AVIADO DOMINGO M. , SADAVONGVIVAD CHIRAVAT
Published: July 2012

. The noradrenaline concentration in the lung was less than 0·5 μg/g in eight animal species.

. In the cat, dog, rabbit and goat, tyramine produced a fall in pulmonary resistance, which was reduced by the administration of either reserpine or cocaine. Although an infusion of noradrenaline increased the content of this amine in the lung of the cat, previously depleted by reserpine, the bronchodilator property of tyramine was not restored. The infusion of isoprenaline did not restore the response to tyramine. The role of either catecholamine in mediating the bronchomotor response to tyramine could not be ascertained.

. The concentration of dopamine was as high as 6·4 μg/g in the goat lung and less than 0·5 μg/g in the lungs of the cat, rabbit, dog, rat, mouse, guinea‐pig and man. Dopamine, injected intravenously into the cat, dog, rabbit and goat, produced a slight rise in pulmonary resistance. This increase was blocked by tolazoline, indicating that the response was mediated by α‐adrenoceptors in the bronchial passages. No procedure has been observed to influence the dopamine content of the lung. The release of dopamine cannot, however, be excluded until the blood in the bronchial veins has been analysed.
Temperature modulation of α‐ and β‐adrenoceptors in the isolated frog heart
Authors: BUCKLEY G. A. , JORDAN C. C.
Published: July 2012

. The effects of adrenaline on the isolated frog's heart at 27° C are not antagonized by phentolamine (1·5 × 10−6m) but are abolished at 7° C.

. At 27° C isoprenaline was more potent than noradrenaline, but at 7° C noradrenaline was more potent than isoprenaline.

. Phenoxybenzamine (1·5 × 10−5m) or dibenamine (1·5 × 10−5m) at 7° C abolished the work output induced by adrenaline. When the temperature was raised to 24° C., adrenaline caused an increase in work output.

. It is concluded that in the isolated frog heart there are at least two pools of adrenoceptors, the availability of which can be governed by temperature.
Localization of kininogenase in the rat kidney
Authors: NUSTAD K.
Published: July 2012

. The rat kidney kininogenase (KGA) activity was located mainly in the kidney cortex.

. Differential centrifugation of kidney cortex homogenate revealed that the microsomal fraction contained more KGA activity per unit of protein than the other subcellular fractions.

. Subfractionation of the microsomal fraction showed that the KGA activity was recovered in a subfraction also containing high specific activity of both alkaline phosphate and glucose‐6‐phosphatase. It is suggested that the KGA activity is localized in the plasma membrane and/or endoplasmic reticulum membranes of kidney cortical cells.

. Hydrolysis of N‐α‐benzoyl‐l‐arginine ethyl ester at pH 8.5 paralleled the KGA activity.
Influence of halothane and catecholamines on heart rate and rhythm in the horse
Authors: LEES P. , TAVERNOR W. D.
Published: July 2012

. Ventricular ectopic beats were recorded in eight of thirteen conscious horses following the intravenous administration of adrenaline in doses of 3 μg/kg. Following pre‐treatment with either atropine sulphate (0.1 mg/kg) or propranolol hydrochloride (0.1 mg/kg), the same dose level of adrenaline failed to produce ventricular ectopic beats.

. Halothane anaesthesia sensitized the equine heart to the arrhythmogenic actions of adrenaline; the incidence and duration of ventricular arrhythmias being greater than in conscious animals. In comparison with the findings in conscious horses, ether anaesthesia appeared to protect the heart against adrenaline‐induced arrhythmias.

. From a comparison of the arrhythmogenic, chronotropic and pressor actions of adrenaline, noradrenaline and isoprenaline during halothane anaesthesia, it was concluded that sensitization to the arrhythmogenic actions of catecholamines resulted primarily from the action of halothane on the ventricle. The results also indicated that the pressor responses to catecholamines during halothane anaesthesia probably played some part in the genesis of arrhythmias.

. No “spontaneous” ventricular arrhythmias were recorded in twenty‐four horses anaesthetized with halothane or in sixteen animals under ether anaesthesia.

. The available evidence indicates that a moderate to fairly severe degree of hypercapnia produced little increase in sympathetic control of the myocardium during halothane anaesthesia; the absence of irregularities in ventricular rhythm during halothane anaesthesia were attributed to this factor.
Noradrenaline content of the heart of the adrenal‐demedullated rat
Authors: BORCHARD F. , VOGT MARTHE
Published: July 2012

The noradrenaline (NA) concentration in the “heart” (atria and right ventricle) of male rats was estimated at different periods following adrenal demedullation. For 1–3 weeks after the operation there was, in all rats, a reduction in NA content of the tissue, whereas, after somewhat longer intervals, the concentrations had returned to normal in some but not in all animals, so that the range of values was very wide.

In order to be able to test the effect of 2‐aminotetralin on the cardiac NA of animals deprived of their medulla but having normal initial NA concentrations, an interval of 6–8 months was allowed to elapse between operation and injection of the drug; at this time the effect of the drug on cardiac NA was the same in intact and demedullated animals. There is thus no reason to attribute to the adrenal medulla any supporting role in the resynthesis of cardiac NA during periods of increased sympathetic activity.

The time course of the pronounced fall in cardiac NA after adrenal demedullation resembles the time course of sodium retention shown by Gaunt, Renzi, Gisoldi & Howie (1967) to follow this operation. It is therefore suggested that it is the change in electrolyte metabolism which is responsible for the abnormality of NA storage; both phenomena occur in demedullated but not in adrenalectomized animals.
The action of para‐methoxyphenylethylamine (PMPEA) on monosynaptic reflex transmission in the cat
Authors: WALKER R. J. , WILLIS J. C. , WILLIS W. D.
Published: July 2012

The intravenous injection of para‐methoxyphenylethylamine (PMPEA) into cats produces an increase in the size of the spinal cord monosynaptic reflex. The reflex elevation occurs within 30 s of drug administration, reaches a peak within 2 min, and lasts about 20 min.

The action of PMPEA is similar for extensor (gastrocnemius‐soleus) and flexor (posterior biceps‐semitendinosus) monosynaptic reflexes.

Repeated doses of PMPEA give comparable effects. The degree of monosynaptic reflex elevation is dose related.

The action of PMPEA is antagonized by phenoxybenzamine and by methysergide or cyproheptadine. The combination of phenoxybenzamine with either of the latter is particularly effective in preventing the reflex facilitation by PMPEA.

It is concluded that PMPEA has a central action on the spinal cord. It seems likely that monoaminergic synapses are involved.
Studies on cholinergic transmission in the medial geniculate nucleus
Authors: TEBĒCIS A. K.
Published: July 2012

Studies were made on the effects of iontophoretically and intravenously administered cholinergic antagonists on the synaptic responses of medial geniculate (MG) neurones evoked by stimulation of the auditory cortex, inferior colliculus and mesencephalic reticular formation.

Atropine specifically blocked a proportion of the excitatory responses evoked by stimulating the auditory cortex, inferior colliculus and reticular formation, although it was without effect on some of them.

Neostigmine and eserine facilitated some excitatory synaptic responses evoked by inferior collicular stimulation.

It is suggested that the feline MG nucleus receives excitatory cholinergic, as well as non‐cholinergic, pathways from the auditory cortex, inferior colliculus and lower brain stem. The cholinergic pathways from the auditory cortex may be either corticofugal fibres or recurrent axon collaterals of afferent projections from the MG nucleus to the cortex. Those from the lower brain stem are possibly the cholinesterase‐containing fibres described by Shute & Lewis (1967).
Some derivatives of polyvinylpyridine 1‐oxides and their effect on the cytotoxicity of quartz in macrophage cultures
Authors: HOLT P. F. , LINDSAY H. , BECK E. G.
Published: July 2012

Poly(2‐vinylpyridine 1‐oxide) counteracts the pathogenic effects normally produced when quartz is injected into or inhaled by animals and the cytotoxic effects when quartz is added to macrophage cultures. The protective action of this polymer has been attributed variously to the formation of an adsorbed layer on the quartz particles, complex formation with monosilicic acid produced by the dissolution of quartz, and strengthening of the membranes or microstructures of the cells.

Stereoregular forms of poly(2‐vinylpyridine 1‐oxide), some alkyl derivatives of poly(2‐vinylpyridine 1‐oxide), poly(3‐vinylpyridine 1‐oxide) and poly(4‐vinylpyridine 1‐oxide), a copolymer of 2‐vinylpyridine 1‐oxide and 2‐n‐propenylpyridine 1‐oxide, some poly(1‐methyl‐2‐vinylpyridinium) quaternary salts, and poly(1‐methoxy‐2‐vinylpyridinium iodide), which had previously been synthesized and studied with respect to their viscosities and interaction with silicic acid, were tested for their ability to counteract the cytotoxic effects of quartz in macrophage cultures. The tests were effected both by pretreating the quartz with polymers, and by pretreating the cells.

Every polymer proved active in one or other of these conditions, but several were active in one test but inactive in the other. Some polymer quaternary salts, which do not contain the N‐oxide group, were found to be active. A remarkable difference in activity was found between the two stereoregular forms of poly(2‐vinylpyridine 1‐oxide). Pretreatment of the quartz with some of the polymers increased its cytotoxicity significantly.

Most of the results could be interpreted on the hypothesis that the polymers form an adsorbed layer on the quartz surface, but it is difficult to apply this explanation to two polymers which are inactive when used to pretreat the macrophages but are active when adsorbed on quartz.
Placental transfer of pyridostigmine in the rat
Authors: ROBERTS J. B. , THOMAS B. H. , WILSON ANDREW
Published: July 2012

Carbon‐14 labelled pyridostigmine in single doses was given by intramuscular injection to pregnant rats, and maternal blood, foetal and placental homogenates were examined for total radioactive content, pyridostigmine and its metabolite, 3‐hydroxy‐N‐methyl pyridinium.

The level of radioactivity in all tissues was highest at 15 min and fell to negligible amounts at 24 hr. The concentrations in placenta were similar to those in maternal blood, but there was some indication of retention of radioactive drug in the placenta. The concentrations in the foetus were substantially lower, but the subsequent slow decline in concentration suggests that cumulation of the drug could occur with repeated doses.

The percentage of metabolite in the foetus was considerably higher than in placenta and blood, and the possible reasons for this are discussed.
Rapid histamine assays: a method and some theoretical considerations
Authors: COLQUHOUN D. , TATTERSALL M. L.
Published: July 2012

An automatic method for doing assays on superfused isolated tissues has been developed using the Autoanalyser sample turntable.

Responses in the range used for assays are independent of the preceding responses when elicited at 1 min intervals. A longer interval was found to be necessary when using the conventional immersion method.

The index of precision was similar to that reported for other superfusion methods.

The assay method behaved as though it were assaying histamine selectively in two samples of material released by the anaphylactic reaction of passively sensitized guinea‐pig lung. Responses to anaphylactically released material were also independent of the preceding response at 1 min intervals.

Some theoretical considerations are discussed concerning the arrangement of doses, and the interpolation of results, in 2 + 1 dose assays. The object was to maximize speed while still allowing a valid estimate of the potency and its error.
The isolation of human plasma prekallikrein
Authors: McCONNELL D. J. , MASON BRENDA
Published: July 2012

. The isolation of human plasma prekallikrein was achieved by fractionating human plasma on diethylaminoethyl cellulose (DEAE) in the presence of heparin.

. Heparin was shown to inhibit the activation of prekallikrein during the isolation procedure.

. The isolated prekallikrein fraction had some kallikrein activity which could be inhibited by diisopropylfluorophosphate (DFP) without affecting the ability of prekallikrein to be activated.

. The prekallikrein obtained was functionally pure in that it had no kallikrein inhibiting or activating activity. It was not physico‐chemically pure, the major contaminant being the immunoglobulin IgG.
The effect of some foreign anions on suxamethonium blockade of the isolated rat diaphragm preparation
Authors: HARRIS J. B. , LEACH G. D. H.
Published: July 2012

. The pharmacology of suxamethonium blockade of the rat phrenic nerve‐diaphragm preparation has been studied in the presence of some foreign anions.

. Blockade proceeded in two distinct phases in both normal and modified Krebs solution.

. In normal Krebs solution the characteristics bore no close resemblance to either depolarizing or competitive type blockade.

. In the presence of foreign anions the characteristics of the blockade more closely resembled those of depolarization.

. There was an increase in the sensitivity of the motor end‐plate region of the muscle to the depolarizing action of acetylcholine, carbachol and suxamethonium in the presence of the anions.

. Although the anions enhanced the depolarizing activity of suxamethonium, the blocking potency of the drug was unaltered.

. It is suggested that end‐plate depolarization plays little part in suxamethonium blockade of the isolated rat diaphragm and that desensitization is the primary cause of the blockade.
β‐Adrenoceptive responses in the unanaesthetized ovine foetus
Authors: PETTEN G. R. Van , WILLES R. F.
Published: July 2012

. Isoprenaline injection into either the unanaesthetized ovine foetus or the pregnant ewe produced a transient tachycardia and hypotension in either the ewe or the foetus. No evidence was obtained for placental transfer, in either direction, of pharmacologically active isoprenaline.

. Propranolol, when given to the ewe intravenously, produced bradycardia and increased pulse pressure and inhibited the response of both the ewe and her foetus to isoprenaline. Propranolol, when given to the foetus intravenously, produced bradycardia and increased pulse pressure in both the foetus and the ewe, but only the foetal response to isoprenaline was inhibited. These data demonstrated that propranolol crossed the ovine placenta in both directions in a pharmacologically active form.

. Dose‐heart rate curves of the foetus and pregnant ewe to isoprenaline and the shift to the right of the isoprenaline dose‐response curves by propranolol were similar in both the ewe and the foetus.

. Notwithstanding the similarities between the ewe and foetus in their responses to isoprenaline or propranolol and in the antagonism of isoprenaline by propranolol, the duration of blockade following propranolol administration to the ewe was 2 to 3 times longer in the foetus compared with the ewe.

. Measurement of blood levels of propranolol showed that the maximum concentration of propranolol in foetal plasma was only 5% of that in the pregnant ewe when propranolol was infused into the ewe; the rate of clearance of propranolol was similar from the foetal and maternal plasma.

. From these data the long duration of β‐adrenoceptor blockade in the ovine foetus by propranolol cannot be fully explained. However, these data serve as examples of the dangers involved when extrapolating pharmacological actions of drugs on the foetus purely from data on foetal plasma levels of the drug.

. The data suggest that multiple doses of propranolol, given to maintain a β‐adrenoceptor blockade in the mother, could result in serious cumulative effects in the foetus.
The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats
Authors: HEIKEL T. A. J. , LATHE G. H.
Published: July 2012

. The effect of oestrogens and progestogens and their 17α‐ethinyl derivatives on bile flow, maximum rate of bilirubin secretion, serum and liver bilirubin has been studied.

. Both 17α‐ethinyl substituted oestrogens and progestogens greatly reduced the basal bile flow. The parent compounds, oestradiol‐17β and 19‐nortestosterone had little or no effect.

. A much larger dose of progestogens (40 mg/kg) than oestrogens (5 mg/kg) was needed.

. Between 12 and 48 h were required for 17α‐ethinyloestradiol to produce the effect.

. Bilirubin maximum secretion rate (Tm) was little affected, the only significant reduction being produced by the 3‐methyl ether of 17α‐ethinyloestradiol (mestranol).

. Rises in serum conjugated bilirubin following infusion of bilirubin were produced by 17α‐ethinyloestradiol and mestranol but not by the progestogens.
The effects of some drugs which induce agranulocytosis on the metabolism of separated human polymorphonuclear leucocytes and lymphocytes
Authors: McCURRACH P. H. , PARK JUDITH K. , PERRY W. L. M.
Published: July 2012

. Lymphocytes and polymorphonuclear leucocytes were separated from normal human blood by the method of Rabinowitz (1964).

. The oxygen uptake, lactic acid production and glucose uptake of suspensions of these cells in vitro were measured. The values obtained agree with published data using comparable techniques.

. Amidopyrine, chloramphenicol, chlorpromazine, phenylbutazone and thiouracil, in high concentrations, depressed the oxygen uptake of polymorphs, but not that of lymphocytes. With amidopyrine, chlorpromazine and thiouracil significant inhibition was produced by concentrations equal to therapeutic plasma levels. High concentrations of the drugs, except chlorpromazine, stimulated the glucose uptake of lymphocytes but not that of polymorphs. Tetracycline and sulphisoxazole were without effect on either parameter of leucocyte metabolism.

. Because of erythrocyte contamination the lactic acid production of lymphocytes could not be determined. Lactate production by polymorphs was not affected by any of the drugs studied.

. The significance of these results is discussed. It is suggested that there is a relationship between ability to induce agranulocytosis and effect on leucocyte metabolism in vitro.
The effect of acetyl strophanthidin on the hearts of normal dogs
Authors: HAYES A. H. , McSHANE W. P. , SIDELL F. R.
Published: July 2012

. The ED50 of acetyl strophanthidin for producing ventricular arrhythmias in normal dogs was 54·5 μg/kg intravenously.

. Doses up to and including those which caused ventricular tachycardia did not produce either atrial arrhythmias or significant aberration of A—V conduction.

. Although the classic digitalis‐induced rate and e.c.g. waveform changes may appear after administration of acetyl strophanthidin, their presence or absence have no value in predicting the subsequent development of ventricular arrhythmias.
Microinjections of tubocurarine, leptazol, strychnine and picrotoxin into the cerebral cortex of anaesthetized cats
Authors: BANERJEE U. , FELDBERG W. , GEORGIEV V. P.
Published: July 2012

. In cats anaesthetized with intravenous chloralose, microinjections of tubocurarine, leptazol, strychnine or picrotoxin, in a volume of 1 μl, were made into the grey matter of the cerebral cortex and the electrical activity was recorded from the site of injection with the microinjection cannula which, insulated except at its tip, served as recording electrode.

. Routinely the injections were made into the gyrus splenialis or into the underlying gyrus cinguli close to the mid‐line, because the injections would then most likely be in grey and not in white matter. Injected in this way all four drugs set up foci of excitation which gave rise to synchronous firing of a large number of neurones with the result that high voltage negative spikes were recorded from the microinjection cannula.

. On injection into the gyrus splenialis the threshold dose was about 004 μg for picrotoxin, about 0·2 μg for tubocurarine, about 5 μg for strychnine and 25 to 50 μg for leptazol. Following the injection of larger doses the spike discharge continued for a few hours after picrotoxin and tubocurarine, for over an hour after strychnine, but for a few minutes only after leptazol. On injection into the gyrus cinguli the threshold doses were slightly greater and with larger doses the spikes occurred at greater frequency but were of lower voltage than in the gyrus splenialis.

. With large doses of picrotoxin injected into the gyrus splenialis the spikes developed an after‐positivity and an after‐discharge which sometimes passed into a short period of fast activity.

. The foci of excitation set up by the drugs were restricted to the site of injection because on raising or lowering the microinjection cannula the spikes recorded from it quickly decreased in voltage and then disappeared. When the injections were made close to a sulcus and the microinjection cannula, on being lowered, traversed the sulcus, the spikes changed their polarity.

. The spike discharge appears to be a consistent response to the injections of the drugs into grey matter of any part of the cerebral cortex since it was also obtained on their injection into the pyriform cortex, amygdala and area retrolimbica anterior, but not on their injection into white matter or caudate nucleus, thalamus or hypothalamus.