bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of morphine dependence on the vesicular content of adrenergic nerves in relation to arteriolar smooth muscle in the pancreas of the rat
Authors: GRAHAM J. D. P. , LEVER J. D. , SPRIGGS T. L. B. 
Published: July 2012

. Sibling male Wistar rats were kept in groups of three under identical conditions. Two groups were made morphine dependent in 28 days and the third served as control. The state of dependence was established by recording the development of tolerance to the analgesic action of the drug and the effect of acute withdrawal of morphine and injection of nalorphine on one test group.
. Animals in the other test group and the control group were killed and specimens of pancreas collected and prepared for examination by electron microscopy. The adrenergic innervation of pancreatic arterioles was located and photographed and the effect of morphinization on the percentage of granular and agranular small vesicles in the axons determined.
. Morphinization produces a significant reduction in the granular or dense core vesicle population of these adrenergic axons.
Factors involved in maintenance of cardiac catecholamine content: relative importance of synthesis and re‐uptake
Authors: BHAGAT B. , FRIEDMAN EITAN 
Published: July 2012

. When animals were exposed to a temperature of 4° C for 6 hr, endogenous catecholamines remained unaltered or reduced slightly depending upon the strain of rats used. In contrast, labelled noradrenaline declined rapidly, but the decline was inhibited when animals were pretreated with monoamine oxidase inhibitors.
. Increased sympathetic nervous activity associated with cold resulted in a four‐fold increase in rate of synthesis of noradrenaline.
. Reduction in endogenous and labelled catecholamine levels associated with cold was exaggerated by pretreatment with cocaine, imipramine or phenoxy‐benzamine—drugs known to inhibit the uptake of noradrenaline into the nerve terminal.
. Cocaine and imipramine in higher doses inhibited the release of both endogenous and labelled noradrenaline, suggesting a dual action: in small doses they increased the depletion of catecholamines by blocking the reincorporation, while in higher doses they inhibited the release of noradrenaline.
. It is concluded that, under normal conditions, the re‐uptake mechanism may not play a significant role in the maintenance of normal cardiac catecholamine levels and that such levels are maintained by synthesis alone. However, when the heart is subjected to high impulse nerve activity, synthesis is not sufficiently accelerated to compensate for impulse‐induced massive release and may require the support of an additional mechanism, such as the partial reincorporation of released transmitter. In fact, the re‐uptake mechanism is enhanced during high impulse activity.
Effects of chronic administration of (+)‐amphetamine on maze performance of the rat
Authors: BREDA J. B. , CARLINI E. A. , SADER N. F. A. 
Published: July 2012

. The influence of (+)‐amphetamine, given 1 min after each training session, on the performance of 124 rats in a Lashley III maze was measured every 48 hr.
. The first three injections of the drug significantly improved the learning ability of naive rats.
. With prolonged treatment, (+)‐amphetamine strongly impaired the maze performance of these rats.
. The chronic administration of (+)‐amphetamine to previously trained rats produced the same adverse effect.
. Amylobarbitone sodium given to previously trained rats 30 min before the training sessions completely blocked the adverse effect of (+)‐amphetamine.
. (+)‐Amphetamine did not produce impairment of performance when given chronically 30 min before training sessions, to previously trained rats.
Antagonism by physostigmine of the “running fit” caused by levorphanol, a morphine congener, in mice
Authors: SHARKAWI MAHMOUD , GOLDSTEIN AVRAM 
Published: July 2012

. Drugs of the morphine type cause a stereotyped “running fit” in the mouse.
. The intensity and duration of this response are related to the dose.
. Measurement of this phenomenon serves as a good method for the quantitative comparison of drugs of this type and for the study of their antagonists.
. Intracerebral injection of physostigmine antagonized the “running fit” induced by a wide range of doses of levorphanol.
. The results are consistent with the hypothesis that drugs of the morphine type act by retarding the release of acetylcholine at some central cholinergic synapses.
Kinin forming and destroying activities in human bile and mucous membranes of the biliary tract
Authors: NIELSEN H. M. 
Published: July 2012

. Human bile and tissue homogenates from the mucous membranes of the biliary tract possess plasma kinin forming activity (kininogenases) and plasma kinin destroying activity (kininases) in varying degrees.
. The common bile duct, especially its lower part, had high kininase activity.
. The liver possessed a high kininase activity, but no kinin forming activity.
. The inactive precursor of plasma kinin, kininogen, was not detected in the bile.
. Results from different pathological conditions are reported.
. The implications of the findings are discussed. Special importance is attached to the question of a formation of kininogenases in the liver and to the significance of a plasma kinin activity in the bile and the biliary tract.
Relationships between chemical structure and affinity for acetylcholine receptors
Authors: ABRAMSON F. B. , BARLOW R. B. , MUSTAFA M. G. , STEPHENSON R. P. 
Published: July 2012

. Series of analogues of acetylcholine have been prepared in which the acetyl group was replaced by phenylacetyl, cyclohexylacetyl, diphenylacetyl, dicyclohexylacetyl, (±)‐phenylcyclohexylacetyl, benziloyl and (±)‐phenyl‐cyclohexylhydroxyacetyl groups and the trimethylammonium group was replaced by Me2EtN+, MeEt2N+, Et3N+,Further series were prepared in which the acetoxyethyl group was replaced by ethoxyethyl, phenylethoxyethyl, cyclohexylethoxyethyl, diphenylethoxyethyl, and dicyclohexylethoxyethyl groups, and by n‐pentyl, 5‐phenylpentyl, 5‐cyclohexylpentyl and 5:5‐diphenylpentyl groups.
. The ethoxyethyl and n‐pentyl series contain some compounds which are agonists or partial agonists when tested on the isolated guinea‐pig ileum, but all the other compounds are antagonists.
. The affinity of the compounds for the postganglionic (“muscarine‐sensitive”) acetylcholine receptors has been measured in conditions in which the antagonists have been shown to be acting competitively. There were considerable differences between their affinities, the most active (log K, 9.8) having one million times the affinity of the least active (log K, 3.7).
. The changes in affinity as the onium group was modified were not entirely independent of changes in the rest of the molecule. Increasing the size of the onium group, as judged from conductivity measurements on simpler onium salts, increased affinity in the series containing one large group (phenyl or cyclohexyl) but, in the series with two large groups, affinity declined when the size was increased beyond ‐N+MeEt2.
. In general, the effects of changes in the rest of the molecule on affinity were bigger than the effects of changes in the onium group and there were bigger interactions. Affinity was increased to a greater extent by introducing one phenyl and one cyclohexyl group together than by introducing either two phenyl or two cyclohexyl groups; the increment was greater than the separate contributions made by one phenyl and one cyclohexyl group.
. The factors which influence the binding of molecules to receptors are discussed. There is no evidence that the separation between the onium group and the group in the receptor with which it interacts is greater in compounds with high affinity nor is there any evidence, from the study of the series which contain agonists and partial agonists, that ability to activate receptors depends upon the onium group being able to come close to this charged group in the receptors.
The action of eledoisin on the peristaltic reflex of guinea‐pig isolated ileum
Authors: BELESLIN D. B. 
Published: July 2012

. Low concentrations of eledoisin, acting from the serosal surface of the guinea‐pig isolated ileum, had no effect on the peristaltic reflex, whereas in high concentrations it depressed or sometimes abolished this reflex.
. Eledoisin stimulated the peristaltic activity of the guinea‐pig ileum subjected to continuously raised intraluminal pressure. This stimulatory effect could be produced regularly when the interval between additions of eledoisin was at least 20 min. When added at shorter intervals, tachyphylaxis to eledoisin developed, but its ability to promote peristaltic activity was restored by the addition of an anticholinesterase to the bath fluid. During tachyphylaxis to eledoisin, nicotine and dimethylphenylpiperazinium were unable to restore peristalsis.
. When the peristaltic reflex had been abolished by ganglion‐blocking agents, morphine and morphine‐like substances, or adrenaline, eledoisin restored the reflex. Eledoisin was much more effective in overcoming the blocking effect of hexamethonium, tetraethylammonium and azamethonium than that of nicotine or dimethylphenylpiperazinium.
. Eledoisin did not antagonize the inhibitory effects of atropine, hyoscine and hyoscine butylbromide.
. It is suggested that the stimulant effect of eledoisin may be due to a direct action on the smooth muscle and a release of acetylcholine from postganglionic nerve endings, but an effect on the intestinal ganglion cells cannot be excluded.
Studies on the mode of action of hexobendine, a prospective anti‐anginal drug
Authors: McINNES LINDA , PARRATT J. R. 
Published: July 2012

. In cats anaesthetized with pentobarbitone sodium, hexobendine (0.25 mg/kg) markedly increased myocardial blood flow (measured using a heat clearance technique) and usually decreased myocardial metabolic heat production, without influencing cardiac contractility or systemic arterial blood pressure. These effects lasted for about 45 min.
. Larger doses (0.5 and 1.0 mg/kg) decreased systemic arterial blood pressure and the rate of rise of the left ventricular pressure pulse (dp/dt), although left ventricular end‐diastolic pressure was usually increased. This is indicative of a decrease in myocardial contractility.
. In a concentration of 5 × 10−6g/ml., hexobendine protected isolated rabbit atria against the decrease in contractility that follows the removal of oxygen.
. Hexobendine did not antagonize the systemic and myocardial effects of infusions of adrenaline and noradrenaline, nor (except in concentrations of 10−5g/ml.) the increase in contractility induced by these catecholamines on isolated rabbit atria.
Comparative study of the effect of three antibiotics on renal function
Authors: CALDWELL A. D. S. , MARTIN A. J. , TRIGGER D. J. 
Published: July 2012

. Therapeutic doses of colistin sulphomethate sodium B.P. (Colomycin), pento‐N sulphomethylpolymyxin B sodium (Thiosporin) and ampicillin B.P. (Penbritin) as well as normal saline have been given to volunteers with normal kidney function.
. A blind crossover technique was used and the effects of the compounds on blood levels and clearances of urea and creatinine studied.
. All four treatments resulted in some changes in the parameters measured but were reversible. The most marked changes were found with pento‐N sulphomethylpolymyxin B sodium and were also associated with severe side‐effects.
. In contrast to penicillins it is established that the process of tubular secretion sensitive to probenecid block plays no part in the renal excretion of polymyxins.
The kinetics of elimination of salicylic acid and the formation of gentisic acid
Authors: BOREHAM D. R. , MARTIN B. K. 
Published: July 2012

. A method for the estimation of gentisic acid in urine has been devised which is based on thin‐layer chromatography and fluorimetry.
. In man the urinary excretion of gentisic acid accounted for 0.6% of a 0.32 g dose of aspirin and 1.1% of a 1.28 g dose. The increase in the percentage of the dose excreted as gentisic acid provides further evidence that the elimination of salicylic acid cannot be entirely described by first order kinetics.
. Equations are presented which describe the amount of gentisic acid formed from various doses of salicylic acid in a model system, when elimination proceeds partly by simultaneous first order and zero order kinetics. The close argeement of the experimental and theoretical results indicates that the model provides an acceptable interpretation of salicylic acid elimination in man.
Studies on the mode of action of vasopressin on the isolated proximal colon of the guinea‐pig
Authors: BOTTING J. H. , TURMER A. D. 
Published: July 2012

. Contractions of guinea‐pig isolated proximal colon produced by vasopressin are not affected by methyloxytocin (a compound that blocks pressor effects of vasopressin).
. Vasopressin contractions are inhibited by replacement of sodium with mannitol or sucrose, elevation of potassium or magnesium concentrations, the presence of the metabolic inhibitors sodium azide and triethyl tin or tetrodotoxin in the bathing fluid. Contractions produced by histamine or choline esters are comparatively insensitive to these procedures.
. Contractions of rat isolated uterus following vasopressin, oxytocin and methacholine are equally affected by replacement of sodium, increase of potassium or magnesium or addition of sodium azide.
. Neither vasopressin contractions nor contractions caused by transmural stimulation were consistently affected by morphine (10−6g/ml.) or hyoscine (10−7g/ml.) although both were reduced by anoxia or cooling the tissue. Morphine did not reduce the output of acetylcholine from stimulated colon.
. It is concluded that the action of vasopressin on proximal colon is unlike its action on other smooth muscle and is mediated by nervous tissue.
Capacitance changes in frog skin caused by theophylline and antidiuretic hormone
Authors: CUTHBERT A. W. , PAINTER ELISABETH 
Published: July 2012

. Impedance loci for frog skins have been calculated by computer analysis from voltage transients developed across the tissues.
. Attention has been paid to simultaneous changes in conductance and capacitance of skins treated either with antidiuretic hormone (ADH) or with theophylline. These drugs always caused an increase in conductance and usually the skin capacitance also increased. However, changes in conductance were not correlated with capacitance changes.
. Changes in capacitance caused by the drugs may represent pore formation in the barrier to water flow, since both drugs increase hydro‐osmotic flow in epithelia. If this interpretation is correct, then 0.14% of the membrane area forms water‐permeable pores in response to a maximal dose of ADH. This value is somewhat less than the value obtained previously (0.3%) by graphical analysis.
. A theoretical account is given of the relative accuracy of the computer method and the graphical method for voltage transient analysis.
Uptake of antimony potassium tartrate by mouse liver slices
Authors: SMITH S. E. 
Published: July 2012

. The uptake of 124Sb‐antimony potassium tartrate by isolated mouse liver slices has been measured and found to establish high tissue: medium concentration ratios.
. Uptake was not influenced by oxygen lack, potassium, ouabain, dinitrophenol or sodium arsenate. It was inhibited by dimercaprol and reduced at low temperature. No evidence was found of counter‐transport. After subcellular fractionation, most of the radioactivity was recovered from particulate fractions.
. Kinetic studies of uptake from media containing different concentrations of antimony suggest that uptake is due partly to diffusion and partly to a saturable binding mechanism, probably involving chelation by non‐diffusible thiol groups. Saturation studies suggest that only a small proportion of thiol groups bind antimony, the remainder undergoing catalytic oxidation.
Effect of β‐haloalkylamines and ephedrine on noradrenaline release from the intact spleen of the cat
Authors: KIRPEKAR S. M. , WAKADE A. R. 
Published: July 2012

The effects of β‐haloalkylamines, phenoxybenzamine (PBZ), N‐α‐naphthyl‐methyl‐N‐ethyl‐β‐bromoethylamine (SY28), N‐cyclohexyl‐methyl‐N‐ethyl‐β‐chloroethylamine (GD131) and ephedrine on noradrenaline (NA) output following nerve stimulation were studied in the intact spleen of the cat. Postganglionic sympathetic nerves were stimulated at frequencies of 10 and 30 Hz for a total of 210 stimuli.
PBZ and SY28 (10 mg/kg) increased the transmitter output at 10 Hz by nearly 5–10 times.
Administration of GD131 (10 mg/kg) had no effect on output at either frequency. Phentolamine (3 mg/kg) given after GD131 increased NA output at 10 Hz.
Ephedrine (0·5 mg/kg) caused no changes in catecholamine output, while higher doses of ephedrine (10–20 mg/kg) increased the amount released at 10 Hz.
Perfusion of the spleen with Krebs‐bicarbonate solution containing either SY28, GD131 or ephedrine (10 μg/ml) increased the recovery of infused NA by 80–90%.
It is concluded that presynaptic as well as postsynaptic events determine the overflow of NA following stimulation of sympathetic nerves of the spleen.
The inactivation of noradrenaline and isoprenaline in dogs
Authors: GRYGLEWSKI R. , VANE J. R. 
Published: July 2012

The removal of infused noradrenaline and isoprenaline from the circulation of the dog has been studied, using the blood‐bathed organ technique.
Both catecholamines were removed in peripheral vascular beds; in all organs studied, noradrenaline was removed to a greater degree than isoprenaline.
The hind legs removed an average of 60% of the noradrenaline passing through, but only 34% of the isoprenaline. With noradrenaline, the degree of removal decreased as the concentration increased, but with isoprenaline, the degree of removal increased with concentration.
After phenoxybenzamine, the proportion of isoprenaline removed was unchanged, whereas that of noradrenaline was decreased. The change in removal with the concentration of noradrenaline was also abolished.
The results are consistent with the concept that a small fraction of infused noradrenaline is removed from the circulation by Uptake1 and that this is blocked by phenoxybenzamine. Isoprenaline, and the rest of the noradrenaline, are removed by another process (Uptake2?) followed by intracellular metabolism. This inactivation process is unaffected by phenoxybenzamine in concentrations sufficient to give α‐adrenoceptor blockade.
After isoprenaline infusions, a substance sometimes appeared in the circulation which contracted the blood‐bathed organs.
The systemic pressure response to vaso‐active hormones is not a reliable indicator of the concentration of hormone in the arterial circulation.
Some central effects in mice of compounds related to nicotine
Authors: BARLOW R. B. , OLIVERIO A. , SATTA M. , THOMPSON G. M. 
Published: July 2012

Some hydroxy‐, amino‐, and methoxy‐ phenylalkyltrimethylammonium compounds, β‐pyridylmethyl‐ dimethylamine and pyrrolidine, and β‐pyridyl>‐ethyltrimethylammonium, were tested on avoidance learning in mice and their effects were compared with those of (–)‐nicotine.
The o‐ and m‐ hydroxybenzyl‐, o‐hydroxyphenethyl‐ and m‐hydroxyphenylpropyl‐ trimethylammonium compounds improved performance; (–)‐nicotine, in one‐quarter of the dose, had similar effects. The m‐ and p‐hydroxyphenethyl‐, o‐hydroxyphenylpropyl‐ and o‐ and p‐ aminobenzyl, and o‐, m‐, and p‐ aminophenethyl‐trimethylammonium compounds impaired performance.
(−)‐Nicotine and m‐hydroxyphenylpropyltrimethylammonium appeared also to enhance memory consolidating processes.
The central actions of some of the compounds suggest that the possibility that they can penetrate into the central nervous system should not be ruled out even though they are quaternary salts.
No correlation was found between the effects of the compounds on avoidance learning and on the frog rectus muscle. Though the differences may be due to differences in access to the central nervous system, it is also possible that the receptors associated with learning processes are different from those in the frog rectus and possibly more specialized.
The relationship between functional vasodilatation in adipose tissue and prostaglandin
Authors: BOWERY N. G. , LEWIS G. P. , MATTHEWS J. 
Published: July 2012

. Earlier it had been found that during fat mobilization there was an increased blood flow in the adipose tissue and the tissue contained a vasodilator substance.
. Extract of an activated fat pad contained 3 to 25 times as much activity as the contralateral resting fat pad.
. The following findings suggest that the vasodilator substance is prostaglandin E2:

It caused contractions of the guinea‐pig ileum which were not reduced by mepyramine, but were reduced by atropine.
It caused a prolonged vasodilator response when injected close‐arterially to the epigastric fat pad.
It was eluted from a silicic acid column by a solvent system which is known to elute prostaglandins of the E series but not those of the F series.
Its indices of discrimination were similar to those of prostaglandin E's when assayed on three different pharmacological preparations.
On thin‐layer chromatography it behaved more like prostaglandin E2 than E1.

. Neither prostaglandin E1 nor prostaglandin E2 inhibited the release of free fatty acids from the rabbit epigastric fat pad by ACTH1–24.
. It seems likely that prostaglandin E2 is responsible for the vasodilatation accompanying fat mobilization from adipose tissue.
Removal of 5‐hydroxytryptamine in the pulmonary circulation of rat isolated lungs
Authors: ALABASTER VALERIE A. , BAKHLE Y. S. 
Published: July 2012

. Rat isolated lungs perfused via the pulmonary artery with Krebs solution removed 92% of the 5‐hydroxytryptamine (5‐HT) infused through it. This degree of removal was independent of concentration in the range from 5 to 100 g/ml.
. The removal of 5‐HT by the lungs was inhibited by amitriptyline and desmethylimipramine (10−6–10−5m).
. The monoamine oxidase inhibitors, mebanazine and iproniazid (10−6–10−5m), inhibited the initial removal slightly, but their main effect was to preserve the 5‐HT taken up and this 5‐HT slowly reappeared in the effluent from the lungs. Tranylcypromine (5 × 10−7–10−6m) showed a combination of amitriptyline‐like and mebanazine‐like effects on the 5‐HT removal in rat lung.
. Experiments with 3H‐5‐HT showed that although under normal conditions only 10% of the radioactivity appeared in the lung effluent as 5‐HT within the first 5 min, the rest of radioactivity administered could be recovered in the effluent over 50 min as a metabolite, probably 5‐hydroxyindoleacetic acid.
. The following amines were without effect on the removal of 5‐HT by rat lungs: noradrenaline (6 × 10−7m), normetanephrine (5 × 10−6m), metaraminol (10−6m), reserpine (10−6–10−5m) and phenoxybenzamine (10−5m).
. We conclude that the removal of 5‐HT by rat lungs involves a process of uptake and metabolism rather than one of uptake and storage, but this process is not the catecholamine Uptake2. The cells involved in this process might be either capillary endothelial cells or septal cells.