bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECTS OF CERTAIN ANAESTHETIC AND ANTI‐CONVULSANT DRUGS ON THE CSF POTASSIUM FLUXES OF THE DOG
Authors: HALLIDAY J. , MOIR A.T.B. 
Published: July 2012

A technique has been developed for open‐ended perfusion of the cerebroventricular system of the unanaesthetized dog.
Perfusion with an artificial CSF solution containing inulin and 42K allowed the potassium fluxes out of and into the CSF to be monitored over a period of 2 to 3 hours.
Sodium thiopentone and sodium pentobarbitone, in doses producing light anaesthesia, caused varying degrees of depression (up to 50%) in the CSF potassium fluxes, influx being consistently more affected than efflux. These effects are attributed to a decrease in the potassium exchange between extracellular and intracellular compartments in the brain.
Diazepam depressed both potassium fluxes by up to 10% while there was some evidence that diphenylhydantoin depressed only potassium influx.
Paraldehyde, in contrast to the other drugs, when given at a dose level sufficient to produce light anaesthesia, stimulated CSF potassium fluxes, particularly efflux.
THE EFFECTS OF ANTICHOLINESTERASES ON SYNAPTIC TRANSMISSION THROUGH NICOTINIC AND MUSCARINIC RECEPTORS IN RAT SYMPATHETIC GANGLIA in vivo
Authors: DREW G.M. , LEACH G.D.H. 
Published: July 2012

Stimulation of the entire spinal sympathetic outflow at supramaximal voltage and 25–100 Hz, in the chlorisondamine‐treated, pithed, adrenalectomized rat produced a delayed pressor response (late pressor response; LPR).
The LPR was abolished by phenoxybenzamine, bretylium or a small dose of atropine (25–50 μg/kg), suggesting the involvement of ganglionic muscarinic receptors.
In the presence of atropine at a dose level (15 μg/kg) which did not influence the LPR, the anticholinesterases physostigmine, neostigmine and Ro 02–0683 but not BW 284C51 markedly enhanced and prolonged the LPR, whereas all of them reduced the pressor responses to AHR‐602.
After blockade of the ganglionic muscarinic receptors with a large dose of atropine (250 μg/kg) the four anticholinesterases did not influence responses to DMPP or noradrenaline and only slightly enhanced responses to preganglionic nerve stimulation at 6 Hz in the absence of chlorisondamine.
It is concluded that inhibition of butyrylcholinesterase accounts for the enhancement and prolongation of the LPR by anticholinesterases.
IMPLICATION OF GASTRIC MUCOSAL HISTAMINE IN INHIBITION BY ISOPRENALINE OF PENTAGASTRIN‐INDUCED GASTRIC SECRETION
Authors: LUNDELL L. , SVENSSON S.E. 
Published: July 2012

The effect of isoprenaline on pentagastrin‐induced gastric secretion was studied in conscious rats with Heidenhain pouches. The influence of isoprenaline on pentagastrin‐induced release and formation of gastric mucosal histamine was also examined.
Isoprenaline strongly inhibited pentagastrin‐induced acid secretion, an inhibition which could not be overcome by increasing the dose of pentagastrin.
Propranolol blocked the inhibitory effect of isoprenaline on pentagastrin‐induced acid secretion.
Isoprenaline enhanced pepsin secretion induced by pentagastrin, an effect which was blocked by propranolol.
Isoprenaline reduced the increase in formation and release of gastric mucosal histamine following pentagastrin infusion, an inhibitory influence which was almost completely blocked by propranolol.
The inhibition by isoprenaline of pentagastrin‐induced acid secretion is tentatively related to alterations in gastric mucosal histamine occurring simultaneously.
ANTAGONISM OF THE EFFECT OF ISOPRENALINE ON HEART RATE BY PILOCARPINE
Authors: SADAVONGVIVAD C. , SATAYAVIVAD JUTAMAAD 
Published: July 2012

The interaction of pilocarpine and isoprenaline on heart rate was investigated in the spontaneously beating, right isolated atrium of the rat.
The log dose‐effect curve of isoprenaline, measured in the presence of various concentrations of pilocarpine, was not modified when the concentration of the latter did not exceed 10−6 m even though significant slowing of the heart had occurred. At concentrations higher than 10−6 m a rapid but graded shift to the right of isoprenaline response curves occurred so that at pilocarpine 10−5 m the pD2 of isoprenaline was reduced from 11 to 3.3; cocaine slightly reduced this antagonism.
It is concluded that pilocarpine antagonizes isoprenaline by some mechanism which is not of the simple competitive type.
ON THE MECHANISM OF ACTION OF CLONIDINE: EFFECTS ON SINGLE CENTRAL NEURONES
Authors: ANDERSON CAROLINE , STONE T.W. 
Published: July 2012

Noradrenaline and clonidine were applied by microiontophoresis to single neurones in the cerebral cortex and medullary reticular formation of anaesthetized rats.
Of a total of 247 neurones studied, 79% of medullary units and 60% of cortical units responded in the same manner to both noradrenaline and clonidine. The usual response was a depression of neuronal firing rate.
It proved possible to antagonize some responses to both substances by the microiontophoresis of bulbocapnine, whilst leaving unaffected similar responses to 5‐hydroxytryptamine.
On 13% of the cells, clonidine produced an increase of firing rate. This effect could not be attributed to a post‐synaptic antagonism of tonically released endogenous noradrenaline, but may indicate a presynaptic action of clonidine, reducing noradrenaline release.
These observations are thought to support the idea that clonidine may have an agonist action on noradrenaline receptors in the brain.
PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL ACTIVITY: THERMODYNAMIC PROPERTIES OF COMPOUNDS RELATED TO ACETYLCHOLINE ASSESSED FROM DEPRESSION OF FREEZING‐POINT AND ENTHALPIES OF DILUTION
Authors: BARLOW R.B. 
Published: July 2012

Measurements have been made of the osmotic coefficients and enthalpies of dilution of acetylcholine and of compounds related to it in which the carbonyl and ether groups have been replaced by methylene and the trimethylammonium group by triethylammonium. All were iodides. Measurements were also made with tetraethylammonium iodide and agree with published values.
Where necessary the affinities of the compounds for acetylcholine receptors in the guinea‐pig ileum and frog rectus, or their activities relative to acetylcholine, have been measured.
The osmotic coefficients were used to calculate activity coefficients and excess free energies, which have been used with the excess enthalpies to calculate the excess entropies of the solutions. These indicate that the ester and carbonyl groups have a marked ordering effect on the ions in water compared with methylene groups; the ether group has an intermediate effect.
When the results are interpreted in terms of ion‐pair formation they can be used to calculate the ion‐association constants and enthalpies and entropies of formation of ion‐pairs, and lead to similar conclusions: that the order associated with ion‐pair formation is greater with the esters and ketones. There appears to be extensive ion‐association in the concentrations (0.5 to 1 m) usually used in n.m.r. studies.
There is no obvious correlation between the effects of groups on water and their activity or affinity at muscarine‐sensitive acetylcholine receptors but it is possible that ability to activate nicotine‐sensitive receptors may be associated with an increase in order, though it would be necessary to study entropy changes in systems actually involving receptors in order to prove this. It is also necessary to suppose that ability to activate these receptors is limited to compounds with small onium groups.
A NEW APPROACH TO THE MEASUREMENT AND CLASSIFICATION OF FORMS OF SUPERSENSITIVITY OF AUTONOMIC EFFECTOR RESPONSES
Authors: KALSNER S. 
Published: July 2012

It is proposed that sensitizations of autonomic effectors to agonists by drugs or procedures be considered in two main categories: those involving changes in the effective concentration of agonist at receptors (type I) and those involving changes in the responding tissue beyond the initial combination of agonist and receptors (type II). Type I sensitizations are appropriately described by determining the dose‐ratio (horizontal shift of the dose‐response curve) and type II sensitizations by assessing the change in the magnitude of the response.
The inadequacy of the dose‐ratio in assessing sensitizations related to an altered physiology of the responding tissue is illustrated by means of hypothetical examples with particular reference to the slopes of dose‐response curves and altered maximal responses.
An evaluation of the enhancement of responses of rabbit aortic strips to agonists by reserpine indicates that it is a type II sensitization. The shifts of dose‐response curves to noradrenaline, isoprenaline, normetanephrine and 5‐hydroxytryptamine after reserpine‐treatment, were described both by the dose‐ratio and by the increment in the magnitude of the response at various contraction amplitudes. The dose‐ratio varied unpredictably for each agonist depending on the response level selected for comparison and also varied between agonists. However, the mm increment in response magnitude after reserpine approximated a constant value. Responses to potassium which by horizontal procedures were assessed among the least increased, were found to be enhanced the most when considered as a type II sensitization.
It is concluded that both type I and type II procedures should be applied when dealing with an unidentified sensitization and that the data be critically assessed. The appropriate use of these procedures can aid in identifying and clarifying sensitizations, as well as in elucidating the sequence of steps between receptor activation and response in an effector.
SPECIFIC SUPERSENSITIVITY OF SMOOTH MUSCLE TO ANGIOTENSIN II AFTER NEPHRECTOMY
Authors: MEYER P. , PAPADIMITRIOU A. , WORCEL M. 
Published: July 2012

The dose‐response curves for angiotensin, 5‐hydroxytryptamine and carbachol were obtained on rat uterus and colon excised 24 h after a bilateral nephrectomy or a sham operation.
There was a shift to the left in the dose‐response curves to angiotensin of organs from nephrectomized animals. Dose‐response curves to 5‐hydroxytryptamine and carbachol were not affected by nephrectomy.
The interaction of the two competitive antagonists (1‐Asn, 5‐Ileu, 8‐Ala)‐angiotensin II and (1‐Asn, 5‐Ileu, 8‐Ileu)‐angiotensin II with angiotensin II receptors was tested in control and nephrectomized organs. There was a decrease of the KI values in colon muscle after nephrectomy.
In conclusion, nephrectomy produces a specific supersensitivity to angiotensin that seems to be due to a change in the structure of angiotensin receptors, at least in colon smooth muscle. This increase in sensitivity may be the result of the elimination of a tropic factor that acts on angiotensin receptor sites.
EVIDENCE FOR PROSTAGLANDIN MEDIATED PREJUNCTIONAL CONTROL OF RENAL SYMPATHETIC TRANSMITTER RELEASE AND VASCULAR TONE
Authors: FRAME MADELINE H. , HEDQVIST P. 
Published: July 2012

Prostaglandin E2 dose‐dependently and reversibly inhibited the noradrenaline overflow resulting from nerve stimulation of the rabbit kidney.
The magnitude of this inhibition varied inversely with the frequency of stimulation employed.
The prostaglandin synthesis inhibitors, indomethacin and meclofenamic acid, both increased the transmitter overflow resulting from renal nerve stimulation, suggesting that endogenous prostaglandin has a role in the regulation of transmitter release.
In the presence of indomethacin, the inhibitory effect of exogenous prostaglandin E2 was enhanced.
The prostaglandin precursor, arachidonic acid, also caused a significant, dose‐dependent and reversible inhibition of transmitter overflow. This inhibition became insignificant when arachidonic acid was applied in the presence of indomethacin, suggesting that the inhibition was mediated by newly formed prostaglandin rather than by arachidonic acid itself.
It is proposed that newly formed prostaglandin controls noradrenaline release primarily from inner cortical nerve endings, thereby maintaining juxtamedullary blood flow under periods of increased sympathetic nerve activity.
EFFECT OF AMODIAQUINE ON GASTRIC HISTAMINE METHYLTRANSFERASE AND ON HISTAMINE‐STIMULATED GASTRIC SECRETION
Authors: BARTH H. , LORENZ W. , TROIDL H. 
Published: July 2012

Amodiaquine was found to be a potent inhibitor in vitro of gastric histamine methyltransferase from human and canine corpus and from pig antrum. The ID50 for the enzyme, purified from pig antrum mucosa by ultracentrifugation and chromatography on DEAE‐cellulose, was 2.5 μM.
In six dogs with Heidenhain pouches the maximum secretory response to histamine (40 μg/kg i.m.) was augmented by i.m. injection of amodiaquine. The augmentation depended on the dose of amodiaquine, the optimum effect (40% increase in volume of gastric juice, 80% in acid output) being achieved with 2 mg/kg. The maximum secretory response to betazole was also enhanced by amodiaquine.
It was suggested that amodiaquine may enhance the histamine and betazole stimulated gastric secretion by an inhibition of gastric histamine methyltransferase in vivo.
CALCIUM AND PANCREATIC SECRETION‐DYNAMICS OF SUBCELLULAR CALCIUM POOLS IN RESTING AND STIMULATED ACINAR CELLS
Authors: CLEMENTE F. , MELDOLESI J. 
Published: July 2012

Pulse‐chase experiments were carried out on pancreatic tissue lobules incubated in vitro, with 45Ca as the tracer, in order to shed some light on the functional significance of the calcium pools associated with the various cell organelles of the acinar cell, especially in relation to stimulus‐secretion coupling.
The kinetics of tracer uptake and release which were observed in the intact lobules suggest the existence of a number of intracellular pools, whose rate of exchange is slower than that across the plasmalemma.
The various subcellular fractions accumulate the tracer in different amounts: some (rough microsomes and postmicrosomal supernatant) showed little radioactivity and some (smooth microsomes and zymogen granule membranes) were heavily labelled; mitochondria and zymogen granules showed intermediate values.
The fractions are heterogeneous also in relation to the time course of uptake and release of the tracer: in rough and smooth microsomes and, especially, in the postmicrosomal supernatant both rates were fast; zymogen granules and zymogen granule membranes showed slow rates of uptake and little release during chase; intermediate rates were found in mitochondria.
In agreement with previous findings we observed that in 45Ca preloaded lobules, stimulation of secretion (brought about by the secretagogue polypeptide caerulein) results in an increase of the tracer release which seems to be due primarily to the rise of the intracellular concentration of free Ca2+ and to the consequent increase of the transmembrane Ca2+ efflux. Among the cell fractions isolated from stimulated lobules only the mitochondria exhibited a significantly lower 45Ca level relative to the unstimulated controls.
It is concluded that, of the organelle‐bound calcium pools, that associated with the mitochondria might be involved in the regulation of the calcium‐dependent functions, including stimulus‐secretion coupling; the calcium associated with the zymogen granule content probably has a role in the architecture of the organelle and in the functionality of the pancreatic juice, while the calcium bound to the membrane of the granules might be concerned with the regulation of its permeability properties.
THE USE OF RADIOACTIVE MICROSPHERES TO COMPARE THE EFFECTS OF HYDRALAZINE, GUANETHIDINE AND SK&F 24260 ON THE REDISTRIBUTION OF CARDIAC OUTPUT IN ANAESTHETIZED RABBITS
Authors: JOHNSTON BARBARA M. 
Published: July 2012

The use of radioactive microspheres is described for the measurement of cardiac output in anaesthetized rabbits and its redistribution after the administration of drugs which lower blood pressure.Hydralazine increased peripheral vascular conductance by 123%. The vascular beds in which it had most effect were those of the carcass (mainly muscle) and the kidneys.SK&F 24260, (1,4 dihydro‐2, 6‐dimethyl‐4‐(2‐trifluormethylphenyl)‐3,5,‐pyridinedicarboxylic acid diethyl ester), had similar vasodilator actions. Its effect in the carcass contributed relatively more to the increase of total peripheral conductance. It also caused a remarkable degree of cerebral vasodilatation.Guanethidine had a relatively small effect on total peripheral conductance and lowered blood pressure mainly by reducing stroke volume and cardiac output.
EFFECTS OF MONOAMINE OXIDASE INHIBITION BY CLORGYLINE, DEPRENIL OR TRANYLCYPROMINE ON 5‐HYDROXYTRYPTAMINE CONCENTRATIONS IN RAT BRAIN AND HYPERACTIVITY FOLLOWING SUBSEQUENT TRYPTOPHAN ADMINISTRATION
Authors: GREEN A.R. , YOUDIM M.B.H. 
Published: July 2012

The effect of various doses of tranylcypromine on the degree of inhibition of rat brain monoamine oxidase (MAO) using 5‐hydroxytryptamine (5‐HT), dopamine and phenylethylamine as substrates has been examined 120 min after injection of the inhibitor. The concentration of brain 5‐HT was also examined both after tranylcypromine alone and also when L‐tryptophan (100 mg/kg) had been given 30 min after the tranylcypromine.
All doses of tranylcypromine greater than 2.5 mg/kg totally inhibited MAO oxidation of 5‐HT, phenylethylamine and dopamine as measured in vitro and produced a similar rise of brain 5‐HT in vivo. When tryptophan was also given, there was a further rise of brain 5‐HT, which was comparable after all doses of tranylcypromine above 2.5 mg/kg and the characteristic syndrome of hyperactivity made its appearance.
Clorgyline (a ‘Type A’ MAO inhibitor), in doses up to 10 mg/kg, did not totally inhibit MAO activity towards phenylethylamine although it did inhibit 5‐HT oxidation by 100%. Deprenil (a ‘Type B’ MAO inhibitor) at doses up to 10 mg/kg did not fully inhibit 5‐HT oxidation although phenylethylamine oxidation was inhibited almost completely. Administration of either compound alone did not produce as great an accumulation of brain 5‐HT as that seen after tranylcypromine (2.5 mg/kg) and subsequent administration of tryptophan did not cause hyperactivity or the rise of brain 5‐HT seen after tranylcypromine (2.5 mg/kg) plus tryptophan.
Administration of clorgyline plus deprenil (2.5 mg/kg of each) almost totally inhibited oxidation of both 5‐HT and phenylethylamine; subsequent tryptophan administration resulted in a rise of brain 5‐HT nearly as great as that seen following tranylcypromine (2.5 mg/kg) plus tryptophan and the animals became hyperactive.
No evidence was found pointing to the formation of any other 5‐substituted indole in the brain following tranylcypromine plus L‐tryptophan administration as suggested by others.
It is concluded that while 5‐HT may normally be metabolized in the brain by ‘Type A’ MAO in vivo, when this form is inhibited, 5‐HT can still be metabolized by ‘Type B’ enzyme. It is only when both forms are almost totally inhibited that the largest rise of brain 5‐HT is seen and subsequent tryptophan administration produces the hyperactivity syndrome.
THE IRREVERSIBLE BINDING OF ACETYLCHOLINE MUSTARD TO MUSCARINIC RECEPTORS IN INTESTINAL SMOOTH MUSCLE OF THE GUINEA‐PIG
Authors: ROBINSON D.A. , TAYLOR J.G. , YOUNG J.M. 
Published: July 2012

Acetylcholine mustard (N‐2‐chloroethyl‐N‐methyl‐2‐acetoxyethylamine), a potent muscarinic agonist, binds virtually irreversibly to muscarinic receptors in longitudinal muscle strips from guinea‐pig small intestine, as shown by the inhibition of the binding of [3H]‐propylbenzilylcholine mustard ([3H]‐PrBCM), an affinity label for the muscarinic receptor.
A value for the apparent binding affinity of acetylcholine mustard and a value for the rate constant for the receptor alkylation reaction have been deduced from the rate of onset of the inhibition of [3H]‐PrBCM binding.
The kinetic constants obtained may refer largely to the interaction between acetylcholine mustard and the desensitized receptor.
At high concentrations acetylcholine mustard practically abolishes the contractile response to carbachol. At these concentrations acetylcholine mustard appears to have multiple actions on the tissue.
THERMOREGULATORY CHANGES INDUCED BY CHOLINOMIMETIC SUBSTANCES INTRODUCED INTO THE CEREBRAL VENTRICLES OF SHEEP
Authors: JOHNSON K.G. 
Published: July 2012

Thermoregulatory responses have been recorded from Welsh Mountain sheep exposed to warm, neutral or cold environments while injections of cholinomimetic drugs and/or their antagonists have been given into a lateral cerebral ventricle.
Carbachol and physostigmine inhibited panting of animals at high ambient temperature (ta), caused vasoconstriction and initiated shivering at neutral ta, and accentuated shivering at low ta. Rectal temperature (tre) invariably increased. Oxotremorine had apparently identical effects.
Nicotine and another ganglionic stimulant, the quaternary methyl derivative of dopamine, had no effects on thermoregulation.
Atropine given 10 min before injections of carbachol, physostigmine or oxotremorine completely inhibited their hyperthermic effects, but pretreatment with the ganglion‐blocking drug, pempidine, caused no inhibition. The cholinergic synapses that respond to cholinomimetic drugs injected into the lateral cerebral ventricles of sheep are therefore muscarinic and not nicotinic.
When atropine was given to sheep exposed to cold, no detectable reduction of shivering occurred and tre decreased only slightly, even with doses of atropine far greater than needed to inhibit shivering induced by physostigmine. This may be because shivering is controlled by neural pathways unaffected by drugs administered intracerebroventricularly or because the cholinergic synapses activated by physostigmine do not carry the input from cold sensors.
EFFECT OF ACETYLCHOLINE ON CHANGES IN CONTRACTILITY, HEART RATE AND PHOSPHORYLASE ACTIVITY PRODUCED BY ISOPRENALINE, SALBUTAMOL AND AMINOPHYLLINE IN THE PERFUSED GUINEA‐PIG HEART
Authors: CHAMALES M.H. , GOURLEY R.D. , WILLIAMS BETTY J. 
Published: July 2012

Isolated perfused hearts of guinea‐pigs were given graded doses of isoprenaline, salbutamol and aminophylline, both before and during acetylcholine infusion.
The three agonists produced increases in contractile force, heart rate and ventricular glycogen phosphorylase activity.
Acetylcholine, in the concentration used, had no effect on any of the measured variables but did antagonize the effects of the three agonists on contractility and phosphorylase activity. The positive chronotropic responses were unaltered by acetylcholine infusion.
The ratio of the dose required for a standard heart rate response to the dose producing a standard contractile force response was different for each agonist.
The selective antagonism of the contractile response to isoprenaline, salbutamol and aminophylline suggest that different mechanisms are involved in the initiation of positive inotropic and chronotropic responses.