bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of the hamster stomach in vitro as an assay preparation for prostaglandins
Authors: UBATUBA F. B. 
Published: July 2012

Summary
Hamster stomach strips in vitro are useful test preparations for the assay of prostaglandins E and F in the nanogram concentration range. Three‐minute cycles can be used for long periods without spontaneous contractions or significant base‐line instability.
The mean percentage error and the precision index of six 4‐point assays of prostaglandin E2 were 7·8 and 0·057, respectively.
The relative sensitivity to different prostaglandins was E2/E1∼1, E2/F1α∼65 and E2/A1∼400.
These preparations were relatively insensitive to 5‐hydroxytryptamine (prostaglandin E2/5‐HT∼20,000) and histamine (prostaglandin E2/histamine∼200).
These results suggest that the hamster stomach preparation can be used to differentiate between 5‐hydroxytryptamine and prostaglandins.
THE EFFECT OF INDOMETHACIN ON THE CARDIOVASCULAR AND METABOLIC RESPONSES TO E. coli ENDOTOXIN IN THE CAT
Authors: PARRATT J.R. , STURGESS R.M. 
Published: July 2012

The response of pentobarbitone‐anaesthetized cats to the intravenous administration of E. coli endotoxin (2 mg/kg) consisted of acute pulmonary vasoconstriction (3–5 min after the injection) and a secondary shock phase characterized by delayed systemic hypotension, decreased central venous pressure and cardiac output, and metabolic acidosis with arterial lactate levels three to four times normal. Only one of 25 animals survived 6 hours.
Indomethacin (10 mg/kg), administered intravenously 30 min before the endotoxin, reduced both systemic arterial pressure and myocardial blood flow. It abolished the pulmonary vasoconstriction induced by endotoxin.
Indomethacin modified some of the characteristic features of the delayed, endotoxin shock phase. Systemic hypotension was not observed and the blood pressure in the indomethacin‐treated cats 1, 2 and 4 h after endotoxin was 30 mmHg higher than in those cats administered endotoxin alone. The decrease in arterial pH was also significantly delayed. Six out of 15 animals survived 6 hours.
It is suggested that indomethacin may abolish the initial pulmonary hypertension and oedema by antagonizing the release, or vasoconstrictor effect, of histamine and that part of its action during the shock phase is due to inhibition of prostaglandin release.
PROSTAGLANDINS, KININ AND INFLAMMATION IN THE RAT
Authors: THOMAS G. , WEST G.B. 
Published: July 2012

Prostaglandin E1 and bradykinin exert synergistic effects on vascular permeability in rat skin and in rat paws. Prostaglandin E2 is inactive in this respect.
Prostaglandin F2α reduces the bradykinin response in rat skin but not in rat paws. It also markedly reduces the response of the skin to dextran, 5‐hydroxytryptamine and histamine.
Prostaglandin E1 and dextran exert synergistic effects in rat skin when threshold doses of each agent are used.
Rats genetically resistant to dextran fail to respond to intradermal dextran in the presence of prostaglandin E1.
MECHANISM OF THE PRO‐INFLAMMATORY ACTIVITY OF SYMPATHOMIMETIC AMINES IN THERMIC OEDEMA OF THE RAT PAW
Authors: GREEN K.L. 
Published: July 2012

Thermic oedema induced by heating rat paws at 46.5°C was potentiated by local injection of adrenaline, noradrenaline or high doses of isoprenaline. The pro‐inflammatory effect of sympathomimetic amines was antagonized by phenoxybenzamine or phentolamine but not by propranolol.
The subcutaneous space of heated rat paws was perfused with Tyrode solution and the perfusate collected and assayed for bradykinin, bradykininogen, kinin‐forming activity and kininase activity. When adrenaline (0.5 μg/ml) was included in the perfusion fluid, kininase activity of the perfusate was increased by 76% and free bradykinin reduced by 46%.
Increased vascular permeability induced by injection of bradykinin or kallikrein was reduced by adrenaline or noradrenaline, but isoprenaline had no significant effect.
Pretreatment with soya bean trypsin inhibitor (SBTI) or heparin did not antagonize the pro‐inflammatory effect of adrenaline or thermic oedema per se.
Potentiation of thermic oedema similar to that induced by sympathomimetic amines was obtained by injecting paws with vasopressin prior to heating, or by applying a ligature to stop blood flow to the paw for the first 15 min of heating.
Thermistor probes inserted beneath the paw skin showed that sympathomimetic amines increased the internal temperature of heated paws. This was significant, as small changes in temperature had a marked effect on the development of thermic oedema.
It is suggested that sympathomimetic amines potentiate thermic oedema of rat paws heated at 46.5°C by reducing blood flow to the paw, thereby causing a greater rise in paw temperature and consequently greater injury.
THE EFFECT OF LITHIUM AND RELATED METAL IONS ON THE URINARY EXCRETION OF 2‐OXOGLUTARATE AND CITRATE IN THE RAT
Authors: BOND P.A. , JENNER F.A. 
Published: July 2012

Administration of lithium ions to rats, either acutely by intraperitoneal injection or chronically in food, causes increased excretion of 2‐oxoglutarate and citrate.
Chronic administration in food of rubidium and caesium causes decreased excretion of 2‐oxoglutarate and citrate.
The effects described are not due to changes in urine volume, nor pH, nor are they simply related to the excretion of the injected ion.
Acute administration of lithium caused an increased level of 2‐oxoglutarate in kidney and reduced the ratio of glutamate to 2‐oxoglutarate.
Renal gluconeogenesis in slices was only slightly affected by either acute administration of lithium to the animals or by its presence in the incubation medium of renal slices.
STUDIES ON THE CORONARY DILATOR ACTIONS OF SOME ADENOSINE ANALOGUES
Authors: COBBIN L.B. , EINSTEIN ROSEMARIE , MAGUIRE M. HELEN 
Published: July 2012

The cardiovascular actions of 23 adenosine analogues have been examined in anaesthetized open thorax dogs; the analogues were substituted in the 2‐position of the purine ring, or in the exocyclic amino group, or were modified in the imidazole or sugar rings.
The effects of these compounds on coronary blood flow, peripheral blood pressure, and heart rate were compared with those of adenosine.
9‐β‐d‐Arabinofuranosyladenine had no cardiovascular action; the other analogues on intra‐atrial administration caused an immediate increase in coronary blood flow, the magnitude and duration of which varied with the structures of the analogues.
2‐Fluoro‐, 2‐bromo‐, 2‐isobutylthio‐, 2‐ethylamino‐, and 5′‐deoxy‐5′‐chloro‐ adenosines had coronary dilator potencies equal to or greater than that of adenosine. No relationship was found between the dilator potency of the adenosine analogues and their duration of coronary dilator action.
The coronary dilator action of adenosine was potentiated by inosine, 9‐β‐d‐arabinofuranosyladenine, tubercidin, N6‐methyladenosine and 2‐trifluoromethyl‐N6‐methyladenosine.
There was no correlation between the substrate specificities of the shorter‐acting analogues for adenosine deaminase or adenosine kinase and their duration of coronary dilator action.
It is proposed that in the anaesthetized dog, uptake into tissues is a more important mode of removal of adenosine and adenosine analogues from the vascular system than in activation by adenosine deaminase, that the duration of coronary dilator action of the analogues is related primarily to their specificity for the carrier which mediates adenosine uptake, and that the adenosine carrier is not associated with kinase action.
THE RESPONSE OF THE CAT ANOCOCCYGEUS MUSCLE TO NERVE OR DRUG STIMULATION AND A COMPARISON WITH THE RAT ANOCOCCYGEUS
Authors: GILLESPIE J.S. , McGRATH J.C. 
Published: July 2012

The cat anococcygeus muscle is shown to possess a dual innervation similar to the rat anococcygeus, with a motor adrenergic innervation and an inhibitory innervation whose transmitter is unknown. The pharmacological properties of the cat muscle were investigated and compared with those of the rat muscle.
The cat muscle contracts to noradrenaline, 5‐hydroxytryptamine, tyramine, amphetamine, guanethidine, cocaine and lysergic acid diethylamide (LSD). The effects of noradrenaline and 5‐hydroxytryptamine are blocked by phentolamine and methysergide respectively.
The cat anococcygeus is relaxed by acetylcholine, carbachol, isoprenaline, ATP, prostaglandins E1, E2 and F2α and vasopressin, all of which contract the rat muscle. The effects of acetylcholine and carbachol are blocked by atropine and those of isoprenaline by propranolol.
Field stimulation produces contraction of the cat anococcygeus, which is blocked by phentolamine and guanethidine but unaffected by hexamethonium, atropine or neostigmine.
In the presence of guanethidine (10−5m), the tone of the muscle is raised and field stimulation produces relaxation of the muscle. These inhibitory responses are unaffected by phentolamine, hexamethonium, atropine or neostigmine.
Neostigmine potentiates the effects of acetylcholine, but not of carbachol in relaxing the cat anococcygeus and in contracting the rat anococcygeus, but has no effect on either motor or inhibitory responses to field stimulation.
Cold storage for up to eight days had little effect on either the motor response to noradrenaline or the motor or inhibitory response to field stimulation of the cat anococcygeus. Beyond eight days, the response to field stimulation diminishes more rapidly than the response to noradrenaline.
THE EFFECT OF Δ1‐TETRAHYDROCANNABINOL ON THE RELEASE OF [3H]‐(‐)‐NORADRENALINE FROM THE ISOLATED VAS DEFERENS OF THE RAT
Authors: GRAHAM J.D.P. , LEWIS M.J. , LI D.M.F. 
Published: July 2012

The amount of tritium released upon transmural stimulation of the isolated vas of the rat incubated with [3H]‐Δ1‐tetrahydrocannabinol (THC) (2.8 μM) was significantly greater than the non‐stimulated overflow.
There was no difference between non‐stimulated overflow and the effect of transmural stimulation of vasa equilibrated with [14C]‐sorbitol (6.5 mg/ml).
The difference between non‐stimulated and stimulated efflux from vasa equilibrated with [3H]‐Δ1‐THC was abolished in rats pretreated for 24 h with 6‐hydroxydopamine (250 mg/kg).
The amount of tritium released upon transmural stimulation of the vas incubated with [3H]‐noradrenaline (6 μm) was significantly greater than the non‐stimulated overflow.
Δ1‐THC (560 Nm and 14 μm) caused a significant dose‐dependent reduction of both non‐stimulated and stimulated tritium efflux, especially the latter.
THE OUTPUT PER STIMULUS OF ACETYLCHOLINE FROM CEREBRAL CORTICAL SLICES IN THE PRESENCE OR ABSENCE OF CHOLINESTERASE INHIBITION
Authors: BOURDOIS P.S. , MITCHELL J.F. , SOMOGYI G.T. , SZERB J.C. 
Published: July 2012

The release of endogenous acetylcholine (ACh) from cerebral cortical slices stimulated at 0.25, 1, 4, 16 and 64 Hz was measured in the presence either of physostigmine or of physostigmine and atropine.
Atropine potentiated the evoked release of endogenous ACh especially at low frequencies resulting in an output per stimulus which sharply declined with increasing frequency of stimulation, while in the absence of atropine the output of ACh per stimulus was low and fairly constant.
The evoked release of [3H]‐ACh per stimulus following the incubation of the slices with [3H]‐choline, as estimated by means of rate constants of the evoked release of total radioactivity, showed a frequency dependence similar to endogenous ACh when the two were tested under identical conditions.
In the absence of an anticholinesterase the evoked release of [3H]‐ACh per stimulus was dependent on frequency of stimulation in a similar way to that in the presence of physostigmine and atropine.
Results suggest that under physiological conditions, i.e. in the absence of an anticholinesterase, the release of ACh per stimulus decreases with increasing frequency of stimulation and that this decrease is due to a lag in the mobilization of stored ACh rather than in the synthesis of new ACh.
PROTECTION BY PHENTOLAMINE AGAINST THE EFFECTS OF PHENOXYBENZAMINE ON TRANSMITTER RELEASE ELICITED BY NERVE STIMULATION IN THE PERFUSED CAT HEART
Authors: FARAH M.B. , LANGER S.Z. 
Published: July 2012

The effects of cocaine, phentolamine and phenoxybenzamine on neuronal uptake of [3H]‐noradrenaline and on 3H‐transmitter and noradrenaline overflow elicited by nerve stimulation were determined in the perfused heart of the cat.
During perfusion with cocaine 3.4 × 10−7m, there was a 2‐fold increase in transmitter overflow while neuronal uptake of [3H]‐noradrenaline was inhibited by 31.3 ± 2.1%.
After exposure to phenoxybenzamine 8.7 × 10−7m for 20 min and washing with drug‐free solution for 165 min there was an 8‐fold increase in transmitter overflow during nerve stimulation. Under these conditions neuronal uptake of [3H]‐noradrenaline was inhibited by only 17.5 ± 5.4%.
There was no significant change in transmitter overflow or in neuronal uptake of [3H]‐noradrenaline, 155 min after a 30 min exposure to phentolamine (3.2 × 10−5m).
Perfusion with phentolamine (3.2 × 10−5m) before and during exposure to phenoxybenzamine (8.7 × 10−7m), prevented the increase in transmitter overflow observed after perfusion with phenoxybenzamine alone.
Protection by phentolamine against the effects of phenoxybenzamine supports the view that the effects on transmitter release obtained after perfusion with phenoxybenzamine are due to the blockade of presynaptic α‐adrenoceptors which regulate transmitter release through a negative feed‐back mechanism.
THE EFFECT OF PITHING AND OF NERVE STIMULATION ON THE DEPLETION OF NORADRENALINE BY RESERPINE IN THE RAT ANOCOCCYGEUS MUSCLE AND VAS DEFERENS
Authors: GILLESPIE J.S. , McGRATH J.C. 
Published: July 2012

The depletion of noradrenaline (NA) in the rat anococcygeus muscle and vas deferens by reserpine and the effect on this of the abolition of nerve activity by pithing and reinforcement of nerve activity by stimulation of the spinal cord outflows has been studied.
NA depletion of the anococcygeus and vas deferens measured 24 h after reserpine was similar and was related to dose. The heart was depleted faster than the two smooth muscle tissues.
In the absence of reserpine neither abolition of nerve activity by pithing nor its reinforcement by nerve stimulation had a detectable influence on NA content of the anococcygeus or vas deferens.
In rats given reserpine (200 μg/kg), increasing nerve activity by spinal stimulation significantly increased NA depletion in both the anococcygeus and the vas deferens when compared with animals pithed but not stimulated. These results confirm that nerve impulse traffic can be an important factor in determining the rate of depletion of NA by reserpine.
The mechanical response to nerve stimulation in both the vas deferens and anococcygeus was resistant to quite severe depletion of their NA content, with the exception of the initial fast component of the response in the vas. The implications of these results for motor transmission in the vas deferens are discussed.
ERGOMETRINE AND APOMORPHINE AS SELECTIVE ANTAGONISTS OF DOPAMINE IN THE CANINE RENAL VASCULATURE
Authors: BELL C. , CONWAY E.L. , LANG W.J. 
Published: July 2012

Increases in renal blood flow were produced by intra‐arterial injections of dopamine (5–50 μg) in anaesthetized dogs pretreated with α‐ and β‐adrenoceptor antagonists.
Intra‐arterial administration of ergometrine (0.5 mg) or apomorphine (1 mg) produced a depression of the renal dilator responses to dopamine, without affecting renal dilatations in response to intra‐arterial acetylcholine (0.1–1 μg) or histamine (2–50 μg).
The depression of dopamine responses lasted 10–15 min, and was greater with ergometrine than with apomorphine.
It is concluded that both ergometrine and apomorphine can be used as specific blocking agents at vascular dopamine receptors. Ergometrine is the preferred drug for this purpose.
THE ROLE OF SUPERSENSITIVITY TO ACETYLCHOLINE IN THE PRODUCTION OF TOLERANCE TO MORPHINE IN STIMULATED GUINEA‐PIG ILEUM
Authors: SHOHAM SANDRA , WEINSTOCK MARTA 
Published: July 2012

Morphine caused a dose‐dependent reduction in both the height of contraction and acetylcholine release from coaxially stimulated strips of guinea‐pig ileum.
Exposure of the tissue to morphine for 90 min produced acute tolerance to the effect of subsequent doses of morphine on contraction height.
There was no change in the ability of morphine to suppress acetylcholine release.
The responses of morphine‐tolerant ileum to exogenous acetylcholine were enhanced 3 to 10‐fold.
If the ileum did not show tolerance to morphine it did not become more sensitive to acetylcholine.
The results presented suggest that tolerance to morphine could result from a form of disuse supersensitivity.
THE EFFECT OF TRICYCLIC ANTI DEPRESSANTS ON CHOLINERGIC RESPONSES OF SINGLE CORTICAL NEURONES
Authors: BEVAN P. , BRADSHAW C.M. , SZABADI E. 
Published: July 2012

The technique of microelectrophoresis was used in order to study the effects of tricyclic antidepressants on responses of single cortical neurones to acetylcholine.
Both potentiation and antagonism of excitatory responses to acetylcholine could be observed after a brief application of imipramine or desipramine. A higher dose of the antidepressant was required to evoke antagonism than to evoke potentiation.
Responses to carbachol were affected by desipramine similarly, suggesting that inhibition of Cholinesterase is not responsible for the potentiation of cholinergic responses.
A brief application of atropine also had a dual effect on responses to acetylcholine.
It is suggested that the potentiation of excitatory cholinergic responses by atropine and the antidepressants may be due to the blockade of masked inhibitory receptors.
POSSIBLE ROLE OF A β‐ADRENOCEPTOR IN THE REGULATION OF NORADRENALINE RELEASE BY NERVE STIMULATION THROUGH A POSITIVE FEED‐BACK MECHANISM
Authors: ADLER‐GRASCHINSKY EDDA , LANGER S.Z. 
Published: July 2012

The effects of isoprenaline, propranolol and phentolamine, were studied on tritiated noradrenaline overflow elicited by postganglionic nerve stimulation in guinea‐pig isolated atria.
Isoprenaline (1.2 × 10−8) increased while propranolol (1.0 × 10‐7 M) reduced the overflow of tritiated noradrenaline evoked by nerve stimulation. These effects were less than those of phentolamine (3.1 × 10‐6 M), which increased by approximately three‐fold the overflow of [3 H] ‐noradrenaline elicited by nerve stimulation.
Neuronal accumulation of tritiated noradrenaline in guinea‐pig atria was not affected by isoprenaline, propranolol or phentolamine at the concentrations employed in this study.
Isoprenaline (1.2 × 10‐8 M) induced a positive chronotropic effect of about 80% of the maximum. On the other hand, propranolol produced a shift to the right in the frequency‐response curve to nerve stimulation and in the concentration‐response curve to exogenous noradrenaline in guinea‐pig atria.
In the isolated nictitating membrane of the cat, the frequency‐response curve to nerve stimulation was not modified by propranolol, while in the presence of 3.9 × 10−6 m of N,‐2‐(2,6‐dimethylphenoxy)propyl‐N,N,N ‐trimethylammonium (β‐methyl‐TM 10) there was a shift to the right and a depression of slope. Neither propranolol nor β‐methyl‐TM 10 affected responses to exogenous noradrenaline.
The effects of isoprenaline and of propranolol on transmitter release are compatible with the view that in addition to the presynaptic negative feed‐back mechanism for noradrenaline release by nerve stimulation mediated via α‐adrenoceptors a positive feed‐back mechanism exists in adrenergic nerve endings which is triggered through the activation of presynaptic β‐adrenoceptors.
THE ACTION OF AMINOPHYLLINE ON THE ACUTELY TRANSPLANTED DOG HEART: EFFECT OF α‐ AND β‐ADRENOCEPTOR BLOCKADE
Authors: PAOLONI H.J. , WILCKEN D.E.L. 
Published: July 2012

Aminophylline inhibits the coronary vasodilator actions of adenosine. Our previous studies suggested that low dose infusions of aminophylline reduce coronary blood flow in the isolated heart. In the present study we investigated the actions of aminophylline on coronary blood flow and myocardial contractility in a transplanted heart model. Drugs were given by close coronary arterial infusion.
Aminophylline in low doses (200 μg/min) reduced coronary blood flow by 21 ± 2% (mean ± s.e. mean) but did not alter myocardial contractility or heart rate. Higher doses (500 and 1000 μg/min) increased coronary blood flow and myocardial contractility without changing heart rate.
α‐Adrenoceptor blockade with phenoxybenzamine did not affect the response to a low dose of aminophylline (200 μg/min).
Propranolol in doses of 10 and 30 μg/min blocked β‐adrenoceptors but did not change coronary blood flow. The higher dose reduced myocardial contractility.
The effects of a high dose of aminophylline (1000 μg/min) on coronary blood flow were not changed by either α‐ or β‐adrenoceptor blockade, although propranolol (30 μg/min) reduced the augmentation in myocardial contractility.
The results show that when given in doses which do not alter myocardial contractility, aminophylline reduces coronary blood flow in the isolated heart and that this is not mediated through an α‐adrenoceptor mechanism, They also show that the increases in coronary blood flow and positive inotropic effects obtained with higher doses of aminophylline are not mediated through catecholamines and suggest that higher doses of aminophylline have a small direct coronary vasodilator action. The low dose vasoconstrictor response may be produced by inhibition of the coronary vasodilator action of locally produced adenosine.
THE EFFECT OF ANOXIA ON THE VENTRICULAR FIBRILLATION THRESHOLD IN THE RABBIT ISOLATED HEART
Authors: MURNAGHAN M.F. 
Published: July 2012

The ventricular fibrillation threshold (VFT) was measured in the isolated heart of the rabbit perfused via the aorta with McEwen's solution at 37° C by applying a single 10 ms pulse of current during the vulnerable period of late systole. The arrhythmia induced was either fibrillation or a rapid tachycardia.
Gassing the McEwen's solution with 5% CO2 in N2 (anoxia) instead of with carbogen caused a negative inotropic and chronotropic effect and significantly lowered the VFT. Although anoxia releases noradrenaline from the heart the effect of anoxia on the VFT was not prevented by β‐adrenoceptor blockade with propranolol or pindolol or by previous treatment with reserpine.
Perfusion with adenosine (5 μM) which is released from the heart muscle by anoxia, or with dipyridamole (10 μM) which protects the adenosine from binding or destruction by the tissues, or with both combined failed to alter the VFT significantly. Furthermore neither adenosine nor dipyridamole significantly altered the effect of anoxia on the VFT.
Anoxia, adenosine and dipyridamole significantly increased the duration of the induced arrhythmia when compared with that of the controls.
Anoxia and adenosine significantly shortened the vulnerable time, i.e. the minimal time after the R‐wave of the ECG at which the pulse had to be applied to induce the arrhythmia.
Perfusion with the McEwen's solution gassed with 5% CO2 in air (hypoxia) significantly lowered the VFT but the effect was not as great as with anoxia. Isoprenaline when infused lowered the VFT but this effect was not potentiated by hypoxia.
The results indicate that (a) anoxia lowers the VFT in the perfused isolated heart of the rabbit and that this effect is not due to adenosine or noradrenaline released by the anoxia and (b) hypoxia does not sensitize the heart to the arrhythmic effect of isoprenaline.