bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE RELATIONSHIP BETWEEN THE PHARMACOKINETICS, CHOLINESTERASE INHIBITION AND FACILITATION OF TWITCH TENSION OF THE QUATERNARY AMMONIUM ANTICHOLINESTERASE DRUGS, NEOSTIGMINE, PYRIDOSTIGMINE, EDROPHONIUM AND 3‐HYDROXYPHENYLTRIMETHYLAMMONIUM
Authors: BARBER H.E. , CALVEY T.N. , MUIR K.T. 
Published: July 2012

The relationship between the concentration of drug in plasma, the inhibition of erythrocyte acetylcholinesterase and the facilitation of neuromuscular transmission has been studied in the rat after the administration of neostigmine, pyridostigmine, edrophonium and 3‐hydroxyphenyltrimethylammonium (3‐OH PTMA).
After the administration of neostigmine or pyridostigmine, acetylcholinesterase activity recovered only slowly due to the covalent nature of the inhibition. In contrast, recovery from the reversible inhibition caused by edrophonium or 3‐OH PTMA was rapid and showed a direct relationship to the plasma concentration of these drugs.
There was a statistically significant linear correlation between the logarithm of the plasma concentration of the drugs and the increase in the tibialis twitch tension.
The relationship between the inhibition of acetylcholinesterase and the facilitation of neuromuscular transmission was complex. When the enzyme was less than 85% inhibited no facilitation occurred. Between 85% and 98% inhibition, facilitation was linearly related to enzyme inhibition. Above 98% inhibition, facilitation was unrelated to inhibition of the enzyme.
THE EFFECT OF α‐ADRENOCEPTOR ANTAGONISTS AND METIAMIDE ON CLONIDINE‐INDUCED LOCOMOTOR STIMULATION IN THE INFANT RAT
Authors: NOMURA Y. , SEGAWA T. 
Published: July 2012

Subcutaneous injections of clonidine (3.9 × 10−8 mol/kg to 3.9 × 10−6 mol/kg) produced forward locomotion and wall climbing in 7‐day‐old rats in a dose‐dependent manner.
The effect was reduced significantly by a preceding intraperitoneal injection of phentolamine (7.9 × 10−6 mol/kg), phenoxybenzamine (7.4 × 10−6 mol/kg), yohimbine (1.3 × 10−6 mol/kg) or piperoxan (7.4 × 10−6 mol/kg).
The pA2‐values of the antagonists to the clonidine‐induced locomotor hyperactivity were: 5.1 (phenoxybenzamine), 5.2 (phentolamine), 6.4 (yohimbine) and 6.0 (piperoxan).
Metiamide (2.5 × 10−4 mol/kg, 5.0 × 10−4 mol/kg and 1.0 × 10−3 mol/kg), a histamine H2‐receptor blocker, did not affect the clonidine‐induced locomotor stimulation.
It is suggested that the receptors which mediate clonidine‐induced locomotor stimulation could be α‐adrenoceptors but not histamine H2‐receptors in the central nervous system of the infant rat.
EFFECT OF GUANIDINE ON RELEASE OF NORADRENALINE FROM THE PERFUSED SPLEEN OF THE CAT
Authors: HIRSCH J. , KIRPEKAR S.M. , PRAT J.C. 
Published: July 2012

Guanidine increased noradrenaline (NA) output at 5 Hz by 3 to 6 fold, and doubled it at 30 Hz. Onset of maximum activity was slow, and reversal was also slow. Output of NA induced by potassium, sodium deprivation, or tyramine was not affected.
NA output was doubled at low concentrations (1 to 2 mm) of guanidine, but maximal effect was obtained at 4 mm. At 10 mm, spontaneous release was occasionally observed.
The effect of guanidine on NA release was related to the external calcium concentration. Outputs which previously have been shown to be insignificant at 5 Hz in 0.25 and 0.75 mm calcium‐Krebs solution were markedly enhanced by guanidine. Guanidine enhanced release at all calcium concentrations up to 7.5 mm, but maximum output was obtained at 2.5 mm.
Guanidine had no effect on the recovery of intra‐arterially infused NA.
The effects of guanidine and tetraethyl‐ammonium (TEA) on NA release at 5 Hz were additive.
Guanidine reversed the inhibition of NA release by guanethidine during nerve stimulation at 5 and 10 Hz, and the NA output increased nearly 2.5 fold after repeated stimulation of the nerves. Guanidine was less effective in reversing the inhibitory effects of guanethidine on NA release at 30 Hz.
Guanidine did not affect release of catecholamines (CA) from the perfused cat adrenal gland by splanchnic nerve stimulation.
It is suggested that guanidine enhances NA release partly by increasing the influx of calcium into the neurone during an action potential, and also by interfering with intracellular binding of calcium.
THE EFFECTS OF α‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON RESPONSES OF TRANSMURALLY STIMULATED PROSTATIC AND EPIDIDYMAL PORTIONS OF THE ISOLATED VAS DEFERENS OF THE RAT
Authors: BROWN CHRISTINE M. , McGRATH J.C. , SUMMERS R.J. 
Published: July 2012

The effects of α‐adrenoceptor agonists and antagonists on contractile responses of transmurally stimulated prostatic and epididymal portions of the rat isolated vas deferens were examined.Responses to single stimuli consisted of two phases, the first predominant in the prostatic and the second in the epididymal portion. The first phase was resistant to α‐adrenoceptor antagonists but the second was reduced in a dose‐related manner in the order of potency prazosin > azapetine > phentolamine > labetalol > yohimbine.Both phases of the response to a single stimulus were reduced by clonidine but only the first could be reliably restored by yohimbine.Trains of transmural stimuli produced biphasic. responses, an early rapid component predominant in the prostatic and a slower secondary component predominant in the epididymal portion. The effects of α‐adrenoceptor antagonists on these responses were complex. Prazosin produced the most straightforward inhibition of responses with relative resistance of the early rapid component. Only yohimbine and phentolamine produced increases in responses which could be pre‐junctional in origin.The α‐adrenoceptor agonists, oxymetazoline and clonidine, reduced while phenylephrine increased responses to trains of stimuli.These results are discussed in relation to the nature of the innervation of rat vas deferens and the usefulness of the preparation in pharmacological tests for activity at α‐adrenoceptors.
TEMPERATURE COEFFICIENTS OF AFFINITY AND ENTROPIES OF ADSORPTION FOR ENANTIOMERIC PAIRS OF COMPOUNDS ACTING AT MUSCARINIC RECEPTORS IN THE GUINEA‐PIG ILEUM
Authors: BARLOW R.B. , BURSTON K.N. 
Published: July 2012

The affinities of a series of enantiomeric pairs of esters of phenylcyclohexylglycollic acid, of a pair of esters of α‐methyltropic acid and of hyoscyamine methiodide have been measured for the muscarinic receptors of the guinea‐pig ileum at 30° and 37°C and estimates have been made of their free energies, enthalpies and entropies of adsorption.
With (−)‐S‐hyoscyamine methiodide the enthalpy of adsorption is negative whereas with the (+)‐R‐enantiomer it is positive.
With the esters of phenylcyclohexylglycollic acid the size of the onium group appears to be as important as the stereochemical configuration in determining entropy. Large onium groups appear to be associated with an increase in entropy though this can only be measured approximately because of the narrow range of temperature which can be used.
THE EFFECT OF THE AMINOSTEROID, ORG 6001, ON HYPOTHERMIA‐INDUCED VENTRICULAR FIBRILLATION IN THE CAT
Authors: KANE KATHLEEN A. , McDONALD FIONA M. , PARRATT J.R. 
Published: July 2012

The effect of the antidysrhythmic aminosteroid, ORG 6001, on hypothermia‐induced ventricular fibrillation was investigated in cats anaesthetized with pentobarbitone.
ORG 6001 (total dose, 10 mg/kg, by intravenous injection) reduced both the incidence of fibrillation and the temperature at which it occurred. The number of animals that survived to 16°C was increased.
This protective effect of ORG 6001 could not be explained by changes in respiratory acidosis, plasma concentrations of sodium and potassium, or by changes in the action potential of excised hypothermic ventricular muscle. The hypothermia‐induced elevation of blood lactate was less in cats treated with the aminosteroid.
Over a limited temperature range, ORG 6001 prolonged the P wave and QRS duration and shortened the QTC interval. ST segment elevation was slightly reduced in the drug‐treated group. J deflections were observed but were not correlated with the development of fibrillation.
The onset of fibrillation was not considered to be due to temperature differences between the myocardium and arterial blood or between localized areas of the left ventricular wall.
COMPARISON OF THE EFFECTS OF A BENZOTRIAZINIUM IODIDE AND QUINIDINE ON GUINEA‐PIG HEART
Authors: FRENCH A.M. , SCOTT N.C. 
Published: July 2012

The actions of 2‐H‐propyl‐4‐p‐tolylamino‐l,2,3‐benzotriazinium iodide (TnPBI) and quinidine were compared on guinea‐pig heart preparations.
Quinidine had negative inotropic and chronotropic effects on guinea‐pig isolated atria and on Langendorff hearts: TnPBI had negative inotropic and chronotropic effects on Langendorff hearts, but showed a positive inotropic effect on isolated atria at low dose levels.
Both quinidine and TnPBI increased the effective refractory period of guinea‐pig atrial preparations.
The effects of TnPBI on transmembrane action potentials indicated a mixed class I and class III action according to the classification of Vaughan Williams (1970).
These effects are discussed in relation to the antiarrhythmic actions of TnPBI.
CARDIOVASCULAR EFFECTS OF HYPERTONIC SODIUM CHLORIDE SOLUTIONS WHEN INJECTED INTO THE LIQUOR SPACE OF ANAESTHETIZED CATS
Authors: FELDBERG W. , WEI E. 
Published: July 2012

In cats anaesthetized with chloralose, hyper‐ and hypotonic solutions were injected into the cisterna magna (in 0.5 ml) or into a lateral cerebral ventricle (in 0.2 to 0.3 ml), with aqueduct cannulated to prevent the injected solution from entering the subarachnoid space, and the effects on blood pressure and heart rate were examined.
Cisternal injections of hyper‐ and hypotonic solutions of NaCl (0.51 m and 0.05 m), glucose (1.03 m and 0.10 m), or sucrose (1.02 m and 0.10 m), as well as distilled water produced a rise in arterial blood pressure with tachycardias. Isotonic solutions of NaCl, glucose or sucrose were ineffective.
Ventricular injections of the hypertonic NaCl solution, also produced a pressor response with tachycardia as did an equally hypertonic solution of NaHC03 but the other solutions produced no circulatory effects when injected in this way.
The pressor responses and the tachycardias occurred after bilateral vagotomy and resulted from a sympathetic discharge which, on cisternal injection, originated from structures reached from the subarachnoid space, and on ventricular injection, from structures in the ventricular walls, probably in the hypothalamus.
The stimuli responsible for the discharge, were, on cisternal injection, the changes in osmolarity. and on ventricular injection, the sodium ions.
EFFECTS OF ARACHIDONIC ACID ON RAT GASTRIC ACID SECRETION IN RESPONSE TO DIFFERENT SECRETOGOGUES; INHIBITION OF THESE EFFECTS BY INDOMETHACIN
Authors: FRAME MADELINE H. , MAIN I. HARVEY M. 
Published: July 2012

The effects of the prostaglandin precursor, arachidonic acid, and the non‐steroidal anti‐inflammatory drug, indomethacin, on gastric acid secretion were studied in the rat, in vivo and in vitro. Gastric mucosal blood flow was also measured in vivo.
Arachidonate produced significant inhibition of acid secretion stimulated by pentagastrin or histamine. It did not significantly affect dibutyryl cyclic adenosine 3′, 5′‐monophosphate (db cyclic AMP)‐induced acid secretion.
Inhibition of acid secretion by arachidonate was accompanied by a rise in the ratio of mucosal blood flow to acid secretion.
Indomethacin did not significantly alter histamine‐ or pentagastrin‐induced acid secretion.
In the presence of indomethacin, the inhibitory effect of arachidonate was significantly reduced.
These results provide evidence that the rat gastric mucosa is capable of synthesizing, from exogenous precursor, products of cyclo‐oxygenase which inhibit gastric acid secretion.
THE RELATIONSHIP BETWEEN NERVE TERMINAL ADENOSINE TRIPHOSPHATASES AND NEUROTRANSMITTER RELEASE: AS DETERMINED BY THE USE OF ANTIDEPRESSANT AND OTHER CNS‐ACTIVE DRUGS
Authors: GILBERT JOHN C. , WYLLIE MICHAEL G. 
Published: July 2012

The role of adenosine triphosphatases (ATPases) in neurotransmitter release was studied using nerve terminals (synaptosomes) prepared from rat cerebral cortex as a model.
Amitriptyline, nortriptyline, protriptyline, desipramine and imipramine were found to inhibit ATPases at concentrations of 10−5 m and above. The drugs inhibited both the basal and electrically evoked release of acetylcholine (ACh) and noradrenaline (NA) at concentrations of 10−4 m and above.
At low concentrations of antidepressants (10−8 and 10−7 m) release of NA was enhanced but there was no effect on ACh release.
Other drugs which inhibit Na+, K+‐ATPase increased basal NA release as did drugs which inhibited vesicular Mg2+‐ATPase.
A model is proposed suggesting that transmitter release/re‐uptake depends on (1) active Na+, K+‐ATPase at the presynaptic membrane and (2) an active synaptic vesicular Mg2+‐ATPase.
THE EFFECTS OF VINCRISTINE ON PLATELET AGGREGATION STUDIED BY A FILTER LOOP TECHNIQUE IN THE RAT
Authors: BEE DENISE , LEACH ENID , MARTIN J.F. , SUGGETT A.J. 
Published: July 2012

A method for measuring aggregation of platelets by adenosine diphosphate (ADP) is described using a filter inserted into the flowing aortic blood in the rat.
Repeated infusions of ADP resulted in a fall in the calculated aggregation index without significant changes in the platelet count.
Vincristine (0.05 mg/kg) intravenously caused significant inhibition of ADP‐induced platelet aggregation.
Infusion of ADP caused some peripheral vasodilatation though it is unlikely that this contributed to the effects seen to any great extent.
THE ISOLATED CIRCULAR MUSCLE LAYER OF THE VAS DEFERENS OF THE GUINEA‐PIG
Authors: ANSTEY MARY D. , BIRMINGHAM A.T. 
Published: July 2012

A method is described for the removal of the outer longitudinal layer of muscle from the guinea‐pig isolated vas deferens. The remaining tube of circular muscle was perfused at constant flow for recording changes in pressure in response to transmural electrical stimulation or to drugs.
The response to transmural stimulation was a rise in perfusion pressure at frequencies of stimulation of 5 to 50 Hz for trains of 16 to 256 pulses. At some frequencies and train lengths a second rise in pressure (the after‐response) occurred after the cessation of the stimulus train.
Perfused vasa stripped of their longitudinal muscle did not develop longitudinal tension on electrical stimulation nor on intraluminal or extraluminal exposure to agonists.
Stripped perfused vasa gave concentration‐dependent pressure rises to noradrenaline but not to acetylcholine.
Responses to transmural stimulation and to noradrenaline were antagonized by thymoxamine. Cocaine or desmethylimipramine increased the duration of the after‐response to transmural stimulation. Reserpine pretreatment almost abolished the response and after‐response. The after‐response, but not the response, was increased by physostigmine and antagonized by atropine.
The results are discussed in relation to the known histochemical and electronmicroscopical demonstrations of dense noradrenergic and cholinergic populations of nerve terminals in the circular layer. It is suggested that mechanisms may exist for the separate control of the longitudinal and circular layers as a basis for propulsive activity.
α‐SYMPATHOMIMETIC AMINES AND CALCIUM‐MEDIATED ACTION POTENTIALS IN GUINEA‐PIG VENTRICULAR MUSCLE
Authors: LEDDA F. , MANTELLI L. , MUGELLI A. 
Published: July 2012

The ability of amines, having α‐ or α‐ and β‐ adrenoceptor stimulating activity, to restore excitability and contractility in heart preparations partially depolarized by potassium, was investigated in guinea‐pig ventricular muscle in order to elucidate the mechanism of the positive inotropic effect mediated via α‐adrenoceptors.
In preparations in which fast sodium channels were inactivated by K+‐rich medium (22 mm) slow electrical responses as well as contractions were consistently induced by high concentrations of phenylephrine (10−4 to 3 × 10−4 m) and synephrine (3 × 10−4 m).
The restorative effects of both phenylephrine and synephrine were unaffected by phentolamine (10−5 m) but were readily abolished by practolol (10−5 m) or sotalol (10−5 m).
Methoxamine induced a dose‐dependent positive inotropic effect in ventricular strips paced at 0.5 Hz in normal Tyrode solution; the maximum increase in contractile tension was obtained with methoxamine 10−4 m. However, at the same concentration, the amine did not induce slow electrical responses in potassium‐depolarized preparations.
It is concluded that the induction of slow responses by phenylephrine and synephrine is due to β‐adrenoceptor stimulation, and that the increase in cardiac contractility caused by α‐adrenoceptor stimulation does not involve an increase in slow inward calcium current.
FACILITATION OF SYMPATHETIC NEUROTRANSMISSION IN THE RAT ANOCOCCYGEUS MUSCLE BY PROSTAGLANDINS D2 AND F2α
Authors: BEDWANI J.R. , HILL SIAN E. 
Published: July 2012

Investigations were made into the effects of prostaglandins D2 (PGD2) and F2α (PGF2α) on the responses of the rat anococcygeus muscle to field stimulation of intrinsic motor (sympathetic) and inhibitory nerves, and to exogenous noradrenaline.
PGD2 (2.8 × 10−6 mol/1) substantially increased the motor responses to field stimulation at all frequencies tested (2 to 32 Hz), and caused a smaller increase in the responses to noradrenaline.
PGF2α (2.8 × 10−6 mol/1) strongly potentiated the motor responses to field stimulation (2 to 32 Hz) and also to noradrenaline. This prostaglandin had quantitatively similar effects on the responses to both types of stimulus.
PGD2 was without effect on the inhibitory responses evoked by field stimulation in the presence of guanethidine. PGF2α seemed to reduce the inhibitory responses to low frequencies of stimulation (0.5 to 1.5 Hz), but this effect was marginal.
The results suggest that PGD2 facilitates sympathetic neurotransmission in this tissue by both pre‐ and post‐junctional actions. The effect of PGF2α seems likely to be mediated predominantly post‐junctionally.
INHIBITION OF REFLEX VAGAL BRADYCARDIA BY A CENTRAL ACTION OF 5‐HYDROXYTRYPTOPHAN
Authors: TADEPALLI A.S. 
Published: July 2012

Vagally mediated reflex bradycardia was elicited in spinal cats with intravenous pressor doses of noradrenaline. Administration of 5‐hydroxytryptophan (1.5 and 3 mg total dose) into the fourth cerebral ventricle reduced the reflex bracycardia.
Inhibition of central amino acid decarboxylase with R044602 prevented the effects of 5‐hydroxytryptophan. After intravenous administration of 5‐hydroxytryptophan, vagal reflex bradycardia was not affected.
Results suggest that 5‐hydroxytryptophan acts in the CNS to inhibit baroreceptor‐mediated vagal reflex bradycardia and that action is mediated via conversion to 5‐hydroxytryptamine.
FURTHER OBSERVATIONS ON THE UTILIZATION OF ADENOSINE TRIPHOSPHATE IN RAT MAST CELLS DURING HISTAMINE RELEASE INDUCED BY THE IONOPHORE A23187
Authors: JOHANSEN TORBEN 
Published: July 2012

The relation between A23187‐induced histamine release and the energy metabolism of the rat mast cells has been studied.
Ethacrynic acid was used as an inhibitor of calcium‐induced histamine release from mast cells primed with the ionophore A23187, and to study calcium‐induced changes in the adenosine triphosphate (ATP) content and the rate of lactate production of A23187‐primed mast cells.
Ethacrynic acid by itself decreased the rate of glycolytic ATP production.
By measurement of the ATP content and the lactate production of mast cells with or without secretory activity, the increased demand of energy for exocytosis was estimated to be equivalent to 0.14 pmol of ATP per 103 mast cells.
THE EFFECT OF LUMBAR SYMPATHETIC STIMULATION ON THE VASCULATURE OF BONE
Authors: TRAN MARIE‐ANTOINETTE 
Published: July 2012

The nutrient artery to the tibia of anaesthetized dogs was perfused at a constant rate by blood from the femoral artery and the perfusion pressure in the artery, the intramedullary pressure of the bone and the pressure in the nutrient vein recorded.
Low frequency stimulation (1 to 5 Hz) of the lumbar sympathetic chain always increased the perfusion pressure but the intramedullary pressure sometimes increased, sometimes decreased and sometimes remained unchanged.
The α‐adrenoceptor blocking agents, phentolamine (1 mg/kg i.v.) and dihydroergotamine (0.5 mg/kg i.v.) reduced or abolished these effects whereas the β‐adrenoceptor blocking agent, propranolol (1 mg/kg i.v.) did not modify them.
The nutrient vein end pressure did not differ significantly from the intramedullary pressure and underwent similar variations during stimulation of the lumbar sympathetic chain.
THE EFFECT OF PROSTAGLANDIN E2 MICROINJECTED INTO THE RAT HYPOTHALAMUS ON URINARY EXCRETION OF WATER AND SODIUM
Authors: FUJIMOTO SEIGO 
Published: July 2012

Effects of prostaglandin E2 (PGE2) microinjected into the supraoptic (SON) and the ventromedial nuclei of the hypothalamus (VMH) on urine outflow were studied in rats anaesthetized with ethanol.
PGE2 injected into the SON caused antidiuresis and increased the excretion rate of Na+. These effects of PGE2 were prevented by pretreatment with phentolamine but not propranolol, suggesting that they are mediated by α‐adrenoceptors in the SON.
PGE2 injected into the VMH caused diuresis and increased the excretion rate of Na+. These effects were prevented by pretreatment with propranolol but not phentolamine, suggesting that they are mediated through β‐adrenoceptors in the VMH.
4‐AMINOPYRIDINE BLOCKADE OF NEURONAL DEPRESSANT RESPONSES TO ADENOSINE TRIPHOSPHATE
Authors: PERKINS M.N. , STONE T.W. 
Published: July 2012

Adenosine, adenosine monophosphate and adenosine triphosphate (ATP) depressed the firing rate of neurones in the rat cerebral cortex when applied by microinontophoresis.
4‐Aminopyridine, also applied iontophoretically, blocked the depressant effects of the purines, without affecting responses to γ‐aminobutyric acid (GABA). This blockade was effected against purine depressions of both spontaneous and glutamate‐evoked activity, suggesting that the interaction occurred postsynaptically.
ACTIONS OF LOCALLY ADMINISTERED ADRENOCEPTOR AGONISTS ON INCREASED PLASMA PROTEIN EXTRAVASATION AND BLOOD FLOW IN GUINEA‐PIG SKIN
Authors: BEETS J.L. , PAUL W. 
Published: July 2012

Bradykinin‐induced increased plasma protein extravasation (IPPE) and blood flow have been assessed in guinea‐pig skin by isotopic methods.
The effects of a range of adrenoceptor agonists on these parameters have been investigated.
α‐Adrenoceptor agonists inhibited IPPE and reduced cutaneous blood flow. The potency of α‐agonists as inhibitors of IPPE correlated with their vasoconstrictor effects. The actions of noradrenaline on both IPPE and blood flow were blocked by phentolamine but not by propranolol.
β‐Adrenoceptor agonists inhibited IPPE at doses which either increased or caused little change in cutaneous blood flow. Isoprenaline inhibition of IPPE was reduced by propranolol but was unaffected by phentolamine.
The inhibitory action of α‐agonists on IPPE can be explained by a reduction in blood flow to the affected site. Beta agonist inhibition is not due to effects on blood flow but is probably caused by a reduction in permeability of the microvessels.
REGULATION OF NORADRENALINE OVERFLOW IN RAT CEREBRAL CORTEX BY PROSTAGLANDIN E2
Authors: HILLIER KEITH , TEMPLETON WILMA W. 
Published: July 2012

The effects of prostaglandin E2 (PGE2), PGF2α and PGI2 and of inhibitors of prostaglandin synthesis and action, on the K+‐evoked [3H]‐noradrenaline ([3H]‐NA) overflow from rat cerebral cortex slices have been investigated.
PGE2 reduced, while indomethacin (a prostaglandin synthesis inhibitor) or SC 19220 (a prostaglandin receptor antagonist) increased, the evoked overflow compared with controls.
The inhibition of [3H]‐NA overflow by PGE2 was dose‐dependently antagonized by SC 19220.
The results indicate that PGE2 modulates NA release in rat cerebral cortex in vitro.