bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors affecting the extraneuronal inactivation of noradrenaline in cardiac and smooth muscle
Authors: BURNSTOCK G. , McCULLOCH M. W. , STORY D. F. , WRIGHT M. E. 
Published: July 2012

Summary
. The relation between density of adrenergic innervation, noradrenaline (NA) accumulation (as seen with the fluorescence histochemical method) in tissues incubated in a high concentration of NA, and monoamine oxidase (MAO) and catechol‐O‐methyl transferase (COMT) activities, were examined in a wide range of tissues from different species.
. Evidence was obtained to support the proposal that accumulation of NA in the non‐innervated smooth muscle of the human umbilical artery and chick amnion is associated with very low activities of COMT within muscle cells.
. The wide variation in tissue accumulation of NA in adrenergically innervated muscles was confirmed. For example, in the rabbit atrium and rat vas deferens, there was high NA accumulation in vascular smooth muscle but not in other muscle cells. In the mouse vas deferens there appeared to be preferential NA accumulation in the outer longitudinal muscle in comparison with the circular muscle. In the ventricle of the rat and mouse individual muscle cells showed different degrees of accumulation of NA. Many unidentified fluorescent cells were revealed in the submucosa of the guinea‐pig ureter following loading with NA. The highest activities of COMT were found in the rat vas deferens and the lowest in the rabbit vascular tissues; the highest activity of MAO was found in the guinea‐pig ileum, and the lowest in the rat aorta.
. No simple relation between tissue activities of MAO and COMT and degree of NA accumulation was found. Possible directions for further investigation of the problem are discussed.
A comparison of the affinities of antagonists for acetylcholine receptors in the ileum, bronchial muscle and iris of the guinea‐pig
Authors: BARLOW R. B. , FRANKS FIONA M. , PEARSON J. D. M. , BUTT ALISON A. 
Published: July 2012

Summary
. Isolated preparations of bronchial strip and of intact iris from the guinea‐pig have been adapted for the measurement of affinity constants of substances which block post‐ganglionic acetylcholine receptors.
. The affinity constants of 28 compounds on bronchial muscle and of 8 compounds on the iris have been compared with values measured on the guinea‐pig ileum.
. Although the compounds differed up to a million‐fold in affinity, most of the estimates of log affinity constant for the bronchial muscle and iris differed only slightly from those on the ileum.
. Some of the differences could be attributed to the actions of hexamethonium, used in the tests on the ileum but not, initially, in the tests with the bronchial strip and iris. Hexamethonium reduced most of the estimates of log K for the receptors in the bronchial strip by a variable but significant amount, which could be due, at least in part, to a weak post‐ganglionic blocking (atropine‐like) action. On average, hexamethonium had little effect on the estimates made with the ileum, appreciably decreasing estimates with some compounds and increasing those with others.
. The results indicate that, although there may be differences between the acetylcholine receptors in the three types of tissue, there is no conclusive evidence, because the differences in affinity which we have observed could have arisen from differences in the experimental conditions. This is illustrated by results obtained with the guinea‐pig ileum recorded with the same technique as was used for the bronchial strip, which are presented as an appendix.
. Such differences as may exist between these three types of acetylcholine receptor are likely to be limited to the replacement of one aminoacid in the receptor protein by a homologue.
Supersensitivity of salivation in response to pilocarpine after withdrawal of chronically administered hyoscine in the mouse
Authors: PARKES M. W. , PARKS JENNIFER C. 
Published: July 2012

Summary
. The duration of the effect of a single large dose of hyoscine, in reducing the salivary response of mice to pilocarpine, was established as less than 66 hours.
. Supersensitivity was observed, after daily oral dosing with hyoscine, in the increased salivation of mice in response to pilocarpine injected at least 66 h after withdrawing hyoscine.
. The minimum duration of pretreatment with hyoscine that resulted in supersensitivity was 5 days. The daily dose was more effective if divided.
. The period after withdrawal for which supersensitivity could be detected was 6 days.
. The maximum salivary response to pilocarpine was increased by chronic hyoscine pretreatment.
. The antagonism of a single dose of hyoscine to pilocarpine salivation, as expressed by the dose‐ratio of pilocarpine, was not altered by chronic hyoscine pre‐treatment.
A myotoxin secreted by some piscivorous Conus species
Authors: FREEMAN SHIRLEY E. , TURNER R. J. 
Published: July 2012

Summary
. Toxins isolated from the venom apparatus of Conus magus and Conus achatinus have the same pharmacological properties, but differ from the toxins of several other piscivorous species of cone shells.
. C. magus and C. achatinus toxins are heat labile at pH 8·5. A single lethal component with an approximate molecular weight of 10,000 was isolated from C. achatinus toxin by exclusion chromatography.
. Animals died from a characteristic spastic paralysis after intravenous injection of the toxin.
. Nerve transmission was unaffected by the toxin; skeletal muscle appeared to be the primary site of action. The toxin caused a persistent contracture of rat diaphragm muscle, and a dose‐dependent decline in twitch tension. The contracture was potentiated by caffeine.
. The decline in twitch tension was associated with depolarization of the cell membrane. Action potential height and the maximum rate of rise declined, and spike propagation failed when the resting potential had declined to approximately 60 mV. The muscle recovered very slowly on washout of the toxin. The depolarization could be reversed by exposure of the preparation to 5 mm Na+ solution or tetrodotoxin or saxitoxin.
. Miniature end‐plate potential frequency in the rat diaphragm decreased, as did the quantal content of the end‐plate potential. The acetylcholine‐induced contraction and depolarization of the chronically denervated rat diaphragm were increased by low doses of toxin and reduced by higher, depolarizing toxin doses. The K+‐induced contraction and depolarization of innervated diaphragm were similarly affected by the toxin.
. Cardiac and smooth muscle were relatively resistant to the toxin. The isotonic contraction of the isolated perfused guinea‐pig heart was increased by the toxins from both Conidae. The heart rate decreased. Guinea‐pig atrial cells showed a small decrease in action potential height and maximum rate of rise. Rabbit sino‐atrial cells showed increases in action potential height, maximum diastolic potential and maximum rate of rise of the spike at low toxin levels, and no change in any of these parameters at high levels. There was a decrease in the rate of the spontaneously beating atrium. Atrioventricular nodal potentials showed no change other than a slight increase in the maximum rate of rise of the action potential.
. It is postulated that the action of the toxin may be related to a change in the Ca++ permeability of the excitable membrane, which makes it unstable, leading to a secondary, depolarizing entry of Na+. The effects of the toxin are compared with those of batrachotoxin, which it somewhat resembles.
Effects of catecholamines and adenosine derivatives given into the brain of fowls
Authors: MARLEY E. , NISTICO G. 
Published: July 2012

Summary
. Adult fowls (Gallus domesticus) with cannulae chronically implanted into the IIIrd cerebral ventricle and various other sites of the brain received micro‐infusions or injections of catecholamines, adenosine, 3′,5′‐cyclic AMP or its dibutyryl derivative. The effects of these substances on behaviour, electrocortical activity and body temperature were studied.
. Behavioural and electrocortical sleep with fall in body temperature were obtained with intraventricular noradrenaline, α‐methylnoradrenaline and isoprenaline; dopamine was ineffective. The doses required to elicit sleep were smaller than those affecting body temperature. Following mebanazine, the effects of noradrenaline were prolonged and doses of dopamine, previously ineffective, lowered body temperature and induced behavioural and electrocortical sleep.
. Noradrenaline, α‐methylnoradrenaline, isoprenaline and dopamine infused into the hypothalamus induced sleep and lowered body temperature. Effective doses of noradrenaline, α‐methylnoradrenaline and isoprenaline infused into the hypothalamus were one‐twentieth to one‐fifth those for intraventricular injection. Tachypnoea developed with isoprenaline and dopamine. Additionally with dopamine, there was deviation of the head to the contralateral side, together with repetitive jerking movements of the head. These effects were prolonged and intensified by mebanazine, whereas the involuntary movements with dopamine were greatly reduced by haloperidol.
. Involuntary movements, but without sleep, were induced by infusing dopamine into the paleostriatum augmentatum; noradrenaline infused into this site was ineffective.
. In three of five fowls pretreated with aminophylline, 3′,5′‐cyclic AMP infused into the hypothalamus induced behavioural and electrocortical sleep; without aminophylline pretreatment, 3′,5′‐cyclic AMP was ineffective. Adenosine infused into the hypothalamus, following pretreatment of fowls with aminophylline, consistently induced behavioural and electrocortical sleep. Dibutyryl cyclic AMP infused into the hypothalamus of intact fowls elicited behavioural arousal, followed by bursts of electrocortical spikes (6 Hz) over both cerebral hemispheres, spikes subsequently becoming regular at 1 Hz. Clonic limb and body movements occasionally accompanied the bursts of spike activity, infrequently developing into convulsions. In fowl encéphale isolé preparations, in which dibutyryl cyclic AMP was infused into the hypothalamus, spike activity was confined to the ipsilateral hemisphere.
Output of prostaglandins from the rabbit kidney, its increase on renal nerve stimulation and its inhibition by indomethacin
Authors: DAVIS HEATHER A. , HORTON E. W. 
Published: July 2012

Summary
. In each of six experiments, prostaglandins were identified in the renal venous blood of the rabbit. The concentrations in renal venous blood were up to 45 times higher than in aortic blood, suggesting that most of the prostaglandins originate from the kidney.
. Prostaglandins E2, F2α and a prostaglandin of the A, C or B series were estimated by biological assay after solvent partition and column or thin‐layer chromatography.
. Prostaglandins E2 and F2α were identified conclusively by combined gas chromatography‐mass spectrometry.
. Electrical stimulation of the renal nerve increased the output of prostaglandins.
. Indomethacin (10 mg/kg) injected intravenously, reduced the output of prostaglandins into renal venous blood and prevented the increase in output on renal nerve stimulation.
Effects of brocresine (NSD‐1055) and cycloheximide on amino acid decarboxylase activities in gastric mucosa of normal and vagally denervated rats
Authors: HÅKANSON R. , LIEDBERG G. 
Published: July 2012

Summary
. Histidine decarboxylase activity of rat stomach fluctuates depending upon the functional state of the stomach. This varying enzyme activity poses special problems in assessing the effectiveness of enzyme inhibitors. After vagal denervation gastric histidine decarboxylase is markedly activated and remains at a high, stable level, which is unaffected by the functional state of the stomach. Thus it appears that vagally denervated rats are well suited for studies on histidine decarboxylase inhibitors.
. In vivo, brocresine (NSD‐1055) was found to be a more effective inhibitor of gastric DOPA decarboxylase than of gastric histidine decarboxylase. With the fairly high dose given (200 mg/kg) the inhibition of histidine decarboxylase was at most 75–85% and quite short‐lasting. The DOPA decarboxylase activity, which was not affected by vagal denervation, was inhibited more than 95% by brocresine; this inhibition was longer‐lasting.
. Cycloheximide, which probably lowers gastric histidine decarboxylase activity by inhibiting enzyme synthesis, was maximally effective at a dose level as low as 1 mg/kg. Gastric DOPA decarboxylase was not inhibited by cycloheximide. Vagotomized rats and control rats responded similarly.
. Combined treatment of vagally denervated rats with brocresine and cycloheximide resulted in a rapid and persistent reduction of the histidine decarboxylase activity. It is concluded that the failure of brocresine alone to induce a lasting inhibition of histidine decarboxylase is due to continuous, rapid synthesis of new enzyme.
. The calculated half‐life of gastric histidine decarboxylase was 75 min in vagally denervated rats and 45 min in normal fasted rats. The results suggest that the increased enzyme activity after vagal denervation is caused by an increased rate of enzyme synthesis.
Effect of drugs on the synthesis of noradrenaline in guinea‐pig vas deferens
Authors: BOADLE‐BIBER MARGARET C. , ROTH R. H. 
Published: July 2012

Summary
. Reserpine in vitro (10−5m) caused a profound inhibition (>85%) of the formation of both 14C‐catecholamine (14C‐CA) and 14C‐dihydroxyphenylalanine (14C‐DOPA) (in the presence of the amino acid decarboxylase inhibitor brocresine) from 14C‐tyrosine in guinea‐pig vas deferens. The magnitude of the inhibition was similar for both 14C‐CA and 14C‐DOPA suggesting that the inhibition occurred primarily at the tyrosine hydroxylase step.
. One hour after in vivo treatment with reserpine (1 mg/kg) when tissue stores of noradrenaline (NA) were depleted by 50%, there was a significant inhibition of the formation of 14C‐DOPA. Twenty‐four hours after such treatment, when endogenous NA could no longer be detected, synthesis of 14C‐DOPA was indistinguishable from untreated controls. However a 45% inhibition of 14C‐DOPA synthesis from 14C‐tyrosine could be produced in tissues which had been depleted of NA for 24 h or 48 h by the addition of reserpine, 10−5m, to the incubation medium.
. Addition of pteridine cofactor, 2‐amino‐6,7,‐dimethyl‐4‐hydroxy‐5,6,7,8‐tetrahydropteridine, to the incubation medium in a concentration of 5 × 10−3m enhanced the formation of both 14C‐CA and 14C‐DOPA from 14C‐tyrosine in guinea‐pig vas deferens. In 52 mm KCl Krebs‐Henseleit medium 14C‐CA formation increased from 2·58 ± 0·20 (nmol/g)/h to 6·35 ± 0·47 (nmol/g)/h whilst 14C‐DOPA formation increased from 5·04 ± 0·88 (nmol/g)/h to 11·29 ± 0·59 (nmol/g)/h.
. Pteridine cofactor (5 × 10−3m) did not reverse the inhibition of 14C‐DOPA formation seen with reserpine (10−5m) in previously untreated tissues or in vasa deferentia from animals pretreated with reserpine 1 mg/kg for 24 hours. However, the inhibition did disappear in the presence of pteridine cofactor when treatment with reserpine was prolonged to 48 h and included two doses of reserpine of 2 mg/kg.
. Tyramine (5·8 × 10−5m) and bretylium (10−5m) in vitro inhibited the formation of 14C‐CA and 14C‐DOPA from 14C‐tyrosine to the same extent in guinea‐pig vas deferens again indicating that their major site of action is on tyrosine hydroxylase. The inhibitory effects were reversed by pteridine cofactor.
. Synthesis of 14C‐NA from 14C‐tyrosine in calf splenic nerve was not increased by incubating the tissue in 52 mm KCl‐Krebs‐Henseleit solution.
The effect of phospholipids on anaphylactic histamine release
Authors: MONGAR J. L. , SVEC P. 
Published: July 2012

Summary
. Histamine release by antigen from three sensitized rat tissues is potentiated by phosphatidyl serine (PS). The effect is greatest with isolated peritoneal cells. Phosphatidyl inositol, ethanolamine, choline and phosphatidic acid are inactive.
. PS greatly increases the rate of antigen‐induced histamine release and only slightly prolongs the duration of the release process.
. PS shows a concentration‐dependent effect over the range 1–10 μg/ml. At 10 μg/ml it is active over a wide range of antigen concentrations.
. Calcium ions are necessary for the potentiation by PS of antigen‐induced histamine release from rat peritoneal cells.
The pharmacology of the rat ureter in vivo
Authors: ANCILL R. J. , JACKSON D. M. , REDFERN P. H. 
Published: July 2012

Summary
A method of recording the peristaltic frequency and the rate of transport of fluid (perfusion rate) in the rat ureter in vivo is described.
Acetylcholine and atropine did not alter ureteral activity. Histamine increased the rate of peristalsis by up to 15% and the rate of perfusion by up to 10%. Low doses of 5‐hydroxytryptamine increased peristaltic frequency whereas high doses decreased peristaltic frequency; all doses reduced the rate of perfusion.
Morphine reduced the rate of perfusion by 5–10% at all dose levels, but only the highest dose used reduced the frequency of ureteral peristalsis.
(—)‐Adrenaline, (—)‐noradrenaline and (±)‐isoprenaline reduced the frequency of peristalsis. The order of potency was isoprenaline>noradrenaline>adrenaline. The response was dose‐related and blocked by propranolol, which itself did not affect ureteral activity.
Effect of tetracyclines and 4‐epiderivatives on the ureter
Authors: ARRIGONI E. , BENZI G. , FERRARA A. 
Published: July 2012

Summary
The effect of tetracyclines on the isolated dog ureter is dependent on: (a) the tetracyclines used—mepicycline and doxycycline antagonizing, and tetracycline and rolitetracycline increasing the contractor action of barium chloride; (b) the percentage of 4‐epiderivatives in the tetracyclines used—the higher the epiderivative concentration, the smaller the effect of mepicycline or doxycycline, and the greater the action of tetracycline or rolitetracycline.
In vivo the addition of the antibiotics into the renal pelvis shows no significant differences between the various tetracyclines or different 4‐epiderivative concentrations on the intra‐ureteral flow of the dog or guinea‐pig.
Intravenous injection of mepicycline or doxycycline does not induce a significant change in the intra‐ureteral flow, while intravenous administration of tetracycline or rolitetracycline produces a triphasic response: (a) a marked decrease of the intra‐ureteral flow for a few minutes; (b) a return to the control condition for 30–60 min; and (c) a lesser but persistent decrease in flow for 60–120 minutes. In the first phase the ureteral smooth muscle is directly affected by the antibiotics circulating in the blood, while in the third phase the tetracyclines act via the intra‐ureteral mucosa.
Neurogenic effects on the ureter‐bladder junction in vivo are not affected by the tetracyclines tested.
Sotalol for the protection of turkeys from the development of β‐aminopropionitrile‐induced aortic ruptures
Authors: SIMPSON CHARLES F. 
Published: July 2012

Summary
The influence of feeding 2 levels of sotalol on the incidence of β‐aminopropionitrile (BAPN)‐induced aortic ruptures of immature turkeys was determined.
Four of 22 turkeys fed 0·12% sotalol and 0·07% BAPN died of aortic ruptures, but 6 of 21 turkeys fed only BAPN died of the syndrome.
Blood pressure, heart rate, aortic tensile strength, and aortic structure as seen by light‐ and electron‐microscope were similar in turkeys fed BAPN alone or both BAPN and 0·12% sotalol concurrently.
In a second experiment, 13 of 24 turkeys fed 0·7% BAPN alone died of aortic ruptures, but only 2 of 24 turkeys fed BAPN and 0·2% sotalol concurrently died of the disease.
Aortic tensile strength was lower, heart rate was faster, alterations of aortic elastic fibres as seen by light‐ and electron‐microscope were more severe, and aortic salt soluble collagen with a higher amino acid content was increased in turkeys fed only BAPN, as compared to turkeys fed both BAPN and 0·2% sotalol.
A neuronal basis for the alerting action of (+)‐amphetamine
Authors: BOAKES R. J. , BRADLEY P. B. , CANDY J. M. 
Published: July 2012

Summary
(+)‐Amphetamine mimicked the excitatory and inhibitory actions of (—)‐noradrenaline on single neurones in the brain stem of acute halothane‐anaesthetized rats when these compounds were applied by iontophoresis. (+)‐Amphetamine had no actions on neurones unaffected by (—)‐noradrenaline.
These mimicking actions of (+)‐amphetamine could not be observed 20 h after treatment of the animals with reserpine 5 mg/kg.
The enzyme inhibitors α‐methyl‐p‐tyrosine and FLA 63 also greatly reduced the number of (—)‐noradrenaline‐mimicking responses to (+)‐amphetamine.
In animals pretreated with α‐methyl‐p‐tyrosine, but not in those pretreated with FLA 63, excitatory actions of (+)‐amphetamine on neurones excited by (—)‐noradrenaline could be elicited 45–90 min after systemic injection of l‐DOPA.
These results indicate that (+)‐amphetamine can release noradrenaline from presynaptic sites in the brain stem, which may be a basis for its alerting actions.
The rat anococcygeus muscle and its response to nerve stimulation and to some drugs
Authors: GILLESPIE J. S. 
Published: July 2012

Summary
A new smooth muscle preparation, the rat anococcygeus muscle, is described. The muscle is paired, thin, consists of smooth muscle only and the muscle cells are organized in parallel bundles. It has a dense adrenergic innervation distributed throughout the muscle but apparently no cholinergic innervation. The muscles are easily isolated.
The muscle contracts to noradrenaline, acetylcholine, furmethide, 5‐hydroxytryptamine, but not to histamine. Isoprenaline produces contraction at high concentrations. The effects of noradrenaline and acetylcholine are blocked by phentolamine and atropine respectively. The response to isoprenaline is little affected by propranolol.
The muscle contracts in response to field stimulation or stimulation of extrinsic nerves. This response is completely blocked by phentolamine but unaffected by hexamethonium or atropine.
Guanethidine 10−6–5 × 10−6M blocks the motor response to nerve stimulation and potentiates that to noradrenaline. Higher concentrations of guanethidine raise tone. In the presence of raised tone, field stimulation produces an inhibitory response insensitive to hexamethonium but abolished by tetrodotoxin 2 × 10−7 g/ml. This inhibitory response to stimulation can also be shown after other drugs which raise tone.
The inhibitory response to nerve stimulation is not mimicked by acetylcholine, isoprenaline or ATP, nor blocked by atropine, phentolamine, phenoxybenzamine, propranolol, hexamethonium or lysergic acid diethylamide.
Fibrinolytic activity evoked in the plasma of the normal and adrenalectomized rat by cellulose sulphate
Authors: ROSA A. T. , ROTHSCHILD A. M. , ROTHSCHILD Z. 
Published: July 2012

Summary
Cellulose sulphate, a kinin‐releasing agent, produced fibrinolytic activity in plasma when administered intravenously to the rat but not when added to fresh rat plasma in vitro. The in vivo effect was maximal within 1 min and disappeared within 10–20 minutes. It was retained in plasma taken 1 min after the injection and kept at room temperature for 30 minutes.
A decrease of anti‐fibrinolytic potency measured against urokinase‐activated bovine plasmin, was shown to occur in plasma of rats given cellulose sulphate.
Activated rat plasma lysed heat‐denatured fibrin: it probably contains free plasmin as well as plasminogen activator.
Adrenalectomized rats did not exhibit fibrinolytic activity nor statistically significant benzoyl‐arginine ethyl ester‐esterase activation in plasma after cellulose sulphate treatment.
Adrenalectomized rats had significantly increased levels of plasma kininogen, but were normally sensitive to the kininogen‐depleting action of cellulose sulphate.
The increased plasma kininogen of adrenalectomized rats seems to be a consequence of the impairment of the plasminogen activating mechanism.