bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic model for the successive demethylation and biliary secretion of methyl orange in the rat
Authors: O'REILLY W. J. , PITT PATRICIA A. , RYAN A. J. 
Published: July 2012

Summary
A one‐compartment pharmacokinetic model was developed in which a drug underwent two successive metabolical reactions (for example, metabolism followed by conjugation) and free drug and both metabolites were excreted.
Techniques were described whereby graphical estimates of the first‐order rate constants may be derived from cumulative excretion data on the drug and its metabolites. Computer simulation techniques were used to show that the experimental data permit reasonably accurate estimation of the rate constants of the model by graphical and computer methods.
Tritiated methyl orange (2 mg) was administered to five groups of six rats with biliary cannulation. The bile produced by each animal was collected at hourly intervals for 6 h and the amounts of methyl orange and its metabolites, 4′sulpho‐4‐methylaminoazobenzene and 4′sulpho‐4‐aminoazobenzene, determined by thin layer chromatography and radioactive counting techniques.
The data were analysed graphically and with an iterative digital computer programme to yield the first‐order rate constants for the successive demethylation steps in the metabolism of methyl orange. The removal of the first methyl group had a rate constant of 0·684 ± 0·142 h−1 (± s.d.) and the second methyl group 1·00 ± 0·302 h−1. The rate constant for biliary excretion of the free methyl orange was 0·164 ± 0·042 h−1, for the monomethyl derivative 0·672 ± 0·461 h−1 and for the demethylated metabolite 6·413 ± 3.222 h−1.
Bretylium potentiation of the contractor responses of isolated rabbit aortic strips to potassium and tyramine
Authors: KURAHASHI K. , SHIBATA S. 
Published: July 2012

Summary
Pretreatment of rabbit aortic strips with bretylium potentiated the contractor response to potassium and tyramine but not to noradrenaline. On the other hand, such pretreatment inhibited the response to nicotine.
Even in reserpinized or cold stored aortic strips, pretreatment with bretylium enhanced the contractor response to potassium and tyramine.
Pretreatment of fresh, reserpinized, or cold stored aortic strips with pheniprazine potentiated the contractor response to potassium and tyramine.
Pretreatment of aortic strips with bretylium or pheniprazine did not potentiate the response to 5‐hydroxytryptamine (5‐HT).
The results indicate that both bretylium and pheniprazine potentiate the action of tyramine and potassium, not by presynaptic mechanisms, but by postsynaptic action, causing an increase in the sensitivity of the effector cells to the stimulants.
Effect of prolonged treatment with tetracosactrin on hypothalamo‐pituitary‐adrenal function in the rat
Authors: HODGES J. R. , MITCHLEY SUSAN 
Published: July 2012

Summary
The functional integrity of the hypothalamo‐pituitary adrenal (HPA) system was assessed in rats after prolonged treatment with tetracosactrin.
Adrenal size and sensitivity to corticotrophin were increased.
Both the circadian rhythm and the stress‐induced increase in HPA activity were inhibited. The circadian rhythm recovered before the response to stress.
Tetracosactrin given after betamethasone treatment delayed the return of a normal HPA response to stress.
Suppression of HPA activity appeared to be the result of a direct action of tetracosactrin and not entirely due to the elevations in the plasma corticosterone concentration which it caused.
Daunorubicin metabolism: estimation of daunorubicin reductase
Authors: BACHUR N. R. , HUFFMAN D. H. 
Published: July 2012

Summary
Daunorubicin reductase, an enzyme ubiquitous in all mammalian tissues tested, converts daunorubicin, a cancer chemotherapeutic antibiotic, to daunorubicinol. A method for the estimation of daunorubicinol and daunorubicin reductase is described.
Daunorubicin and daunorubicinol were quantitatively extracted from enzyme assay mixtures with 0·3 n HCl in 50% ethanol and then completely hydrolysed to their respective aglycones. The aglycones were extracted, concentrated into toluene, separated by silicic acid microcolumn chromatography, and estimated by spectrofluorimetry.
Compared to previous methods, this method is highly reproducible and sensitive.
Relationship between internal Na+/K+ and the accumulation of 14C‐5‐hydroxytryptamine by rat platelets
Authors: SNEDDON J. M. 
Published: July 2012

Summary
5‐Hydroxytryptamine (5‐HT) transport has been investigated in rat blood platelets poisoned with dinitrophenol‐sodium fluoride or ouabain.
The inhibition of transport produced by different concentrations of the metabolic inhibitors has been correlated with changes in the internal Na+ and K+ concentrations of the platelets.
Platelets poisoned in a high K+ medium maintained a high internal K+ concentration in the absence of cellular metabolism. When transferred to Krebs solutions containing different concentrations of Na+ they accumulated 5‐HT by a process that was related to the magnitudes of the internal and external Na+ concentrations.
The results are consistent with the hypothesis that the spontaneous movement of ions through the platelet membrane is capable of providing, at least in part, the energy requirements for 5‐HT transport.
Effect of iontophoretic application of cholinergic agonists and their antagonists to guinea‐pig pelvic ganglia
Authors: HOLMAN MOLLIE E. , MUIR T. C. , SZURSZEWSKI J. H. , YONEMURA K. 
Published: July 2012

Summary
The electrical activity of guinea‐pig pelvic ganglion cells following iontophoretically applied cholinergic drugs, alone and during orthodromic nerve stimulation via the hypogastric nerve, has been recorded intracellularly.
Iontophoretic application of nicotine (Nic) and acetylcholine (ACh) reduced membrane resistance and caused a depolarization which in approximately 80% of cells led to the firing of action potentials. In the remainder, depolarization was unaccompanied by firing.
Iontophoretic application of Nic and ACh reduced or abolished the amplitude of successively evoked orthodromic responses.
ACh‐induced depolarization, unlike that caused by tetanic stimulation, was not followed by a subsequent increase in the frequency of synaptic potentials.
Di‐hydroβerythroidine (DHβE) and atropine (Atr) inhibited the response to both orthodromic stimulation and iontophoretic application of Nic and ACh.
There was no evidence for the existence of muscarinic receptors in guinea‐pig pelvic ganglia. Iontophoretic application of muscarinic agonists alone and after tetanic stimulation of the hypogastric nerve produced no significant depolarization of the ganglion cell membrane.
Cutaneous reactions to intradermal prostaglandins
Authors: CRUNKHORN PEARL , WILLIS A. L. 
Published: July 2012

Summary
The effects of intradermally injected prostaglandins (PGs) E1, E2, F1α and F2α have been examined in the rat and in man.
PGE1 and PGE2 caused an increase in local vascular permeability in rat skin; their potency was comparable with that of other putative mediators of inflammation (histamine, bradykinin, and 5 ‐hydroxytryptamine), but PGF1α and PGF2α were only slightly active even at a dose of 1 μg.
Prior administration of mepyramine and methysergide, or depletion of skin mast cell amines with compound 48/80, indicated that PGE2 exerted its permeability effect in the rat by a release of mast cell amines.
Nanogramme doses of PGE1 and PGE2 or microgramme doses of PGF1α and PGF2α injected intradermally into the human forearm induced weal and flare responses.
It is concluded that prostaglandins E1 and E2 can act as intermediates in the production of hyperaemia and oedema resulting from cell damage in the rat and man.
Action of fenfluramine on monoamine stores of rat tissues
Authors: COSTA E. , GROPPETTI A. , REVUELTA A. 
Published: July 2012

Summary
Fenfluramine is an anorexogenic agent used clinically because it is devoid of central stimulatory effects.
In rats, fenfluramine causes a depletion of 5‐hydroxytryptamine (5‐HT) from the telencephalon + diencephalon which lasts longer than one might have expected from the biological half life of fenfluramine. The depleting effects of fenfluramine do not extend to brainstem, stomach and heart stores of 5‐HT.
Fenfluramine causes an increase in the turnover rate of tel‐diencephalic 5‐HT but such an acceleration could not be detected in the 5‐HT stores of the brainstem.
It is inferred that the effects of fenfluramine on brain 5‐hydroxytryptamine may be related to the accumulation of a fenfluramine metabolite in 5‐HT neurones.
High doses of fenfluramine cause a depletion of catecholamine stores in brain and heart but the time course of this depletion is shorter than the depletion of brain 5‐HT.
Effects of Na+ and K+ on the uptake of metaraminol by rabbit ventricular slices
Authors: PATON D. M. 
Published: July 2012

Summary
The ionic dependence of [3H]‐metaraminol transport by rabbit ventricular slices was studied.
Transport was Na+ dependent. Choline, Li+, K+, Rb+ or Cs+ could not be substituted for Na+.
Transport was K+ dependent. Rb+ and Cs+, but not Li, could be substituted for K+, their relative potencies being K+=or >Rb+>Cs+>Li+. Higher concentrations of K+, Rb+, Cs+ and Li inhibited [3H]‐metaraminol transport.
The inhibitory effects on transport of either a marked reduction in the concentration of Na+ or of omission of K+ were rapidly reversible on exposure of slices to Krebs solution.
The inhibitory effect of ouabain on [3H]‐metaraminol transport was markedly time dependent, being significantly increased by preincubation with ouabain. The inhibitory action of ouabain was not affected, however, by the Na+ concentration present during preincubation.
An inwardly directed Na+ gradient did not increase [3H]‐metaraminol transport in slices in which Na+ pumping had been prevented by 10−5m ouabain, 4° C, omission of K+ or by metabolic inhibition.
These findings provide additional evidence that the Na+ and K+ activated adenosine triphosphatase may participate in the transport of metaraminol and related amines. In the absence of Na+ pumping, induced Na+ gradients were unable to produce transport of amine as would be predicted by the co‐transport model proposed by Bogdanski & Brodie (1969).
Effects of morphine on choline acetyltransferase levels in the caudate nucleus of the rat
Authors: DATTA K. , THAL L. , WAJDA I. J. 
Published: July 2012

Summary
Choline acetyltransferase (choline‐o‐acetyltransferase 2.3.1.6.) concentrations were determined in the caudate nucleus, thalamus, and cortex of control and morphine treated rats. The enzyme was assayed using a modified radiochemical method on a number of selected days, one hour after the last injection of 30 mg/kg of morphine and also during the subsequent phase of abstinence from morphine.
Significant lowering of choline acetyltransferase activity in the caudate nucleus area was found in two cases, one hour after the first dose of morphine and upon subsequent abstinence from morphine.
The enzyme activity in the two other parts of the brain remained at the normal levels.
The presence of endogenous inhibitors formed during morphine administration was excluded.
The relationship of a possible effect of morphine on the tissue binding of the enzyme and the subsequent lowering of its activity was tested by homogenization of the caudate nucleus area in different media. The decrease in enzyme activity occurred in all extraction media one hour after morphine administration.
Inhibitory effects of in vitro addition of morphine to caudate nucleus homogenate, obtained from normal and morphine treated rats, were found to occur only at very high concentrations of the drug, negating the possibility of direct inhibitory effects of morphine.
These experiments suggest two possible causes of the observed effects, which can be responsible for the lowering of enzyme activity, and can be operative simultaneously: (1) a negative feedback mechanism of accumulated acetylcholine, occurring after the first dose of morphine, and (2) the possible changes in enzyme configuration produced by morphine treatment.
Effect of β‐adrenoceptive blocking agents on the response to bronchoconstrictor drugs in the guinea‐pig air overflow preparation
Authors: BURDEN D. T. , PARKES M. W. , GARDINER D. G. 
Published: July 2012

Summary
Propranolol augmented the bronchoconstrictor response to methacholine or histamine, recorded by air overflow in the anaesthetized, vagotomized guinea‐pig.
After adrenalectomy, propranolol was still active, though less so than before.
In the pithed guinea‐pig, there was no augmentation of the effect of bronchoconstrictors on air overflow. The action of propranolol could thus be due to the β‐adrenoceptor blockade of compensatory sympathetic bronchodilator activity, as concluded by McCulloch, Proctor & Rand (1967).
Electrical stimulation of the thoracic region of the spinal cord of the pithed guinea‐pig reduced the effect of bronchoconstrictors on air overflow. This reduction could be blocked by propranolol; practolol was much less effective.
Studies on the inhibition of clearance of organic dyes by Saramycetin
Authors: COONEY D. A. , DAVIS R. D. , HOMAN E. R. , RAKIETEN N. , SCHAEPPI U. , VANATTA G. 
Published: July 2012

Summary
Saramycetin, a polypeptide antifungal antibiotic has been found to retard the clearance of sulphobromophthalein (BSP) in man. An explanation for this observation was sought in several lower species.
Doses of Saramycetin without effect on the other standard tests of hepatic function or on hepatic morphology profoundly altered the disposition of BSP and several other dyes in mice and dogs.
Saramycetin strongly inhibited the hepatic enzyme which conjugates BSP to reduced glutathione, provoked a regurgitation of BSP from the liver into the bloodstream, and was anticholeretic in the dog.
These diverse actions of Saramycetin may, in concert, explain the altered clearance of BSP. It is suggested that low doses of Saramycetin exert a pharmacological effect on certain hepatic excretory processes, whereas high doses are toxic.
The effect of lithium salts on the urinary excretion of α‐oxoglutarate in man
Authors: BOND P. A. , JENNER F. A. , LEE C. R. , LENTON ELIZABETH , POLLITT R. J. , SAMPSON GWYNETH A. 
Published: July 2012

Summary
. Lithium ions in therapeutic doses cause an increase in the renal excretion of α‐oxoglutarate and glutaric acid.
. The excretion is probably due to reduced renal tubular reabsorption.
. Neither citrate, lactate nor pyruvate excretion rises.
The occurrence of tolerance to a central depressant effect of nicotine
Authors: MORRISON CATHLEEN F. , STEPHENSON JANE A. 
Published: July 2012

Summary
. Rats were injected with 0·8 mg nicotine/kg, 0·8 mg amphetamine/kg or with saline immediately before being tested for 30 min in activity boxes.
. During the first 3 trials the nicotine group were less active than the controls but from trial 5 onwards nicotine had a stimulant effect. The stimulant effect of the amphetamine did not alter with repeated injection.
Effects of vasopressin and isoprenaline infusions on the distribution of blood flow in the intestine; criteria for the validity of microsphere studies
Authors: GREENWAY C. V. , MURTHY V. S. 
Published: July 2012

Summary
. The distribution of superior mesenteric arterial flow was investigated by radioactive microspheres. The small intestine received 83% of the flow ((85 ml/min)/100 g intestine) and flow was uniform along the length of the small intestine.
. The intestinal wall was separated into 3 layers—muscle, submucosa and mucosa. The muscle received (8 ml/min)/100 g intestine and the combined submucosa and mucosa (77 ml/min)/100 g intestine.
. The distribution of microspheres between the mucosa and submucosa depended on the size of the microspheres; the smaller the spheres, the more were found in the mucosa. It also depended on the state of the vascular bed; if microspheres were given during an infusion of vasopressin, a subsequent infusion of isoprenaline resulted in movement of some of the spheres from the submucosa into the mucosa.
. Histological studies after India ink injection showed few capillary‐sized vessels but many large vessels in the submucosa. Capillary‐sized vessels arose close to the junction with the mucosa and passed into the mucosa.
. These and other data suggest that the intestine consists of two parallel‐coupled sections, one to the muscle and the other through the submucosa to the mucosa. The vessels in the submucosa are in series with those in the mucosa and submucosal shunts do not exist. Redistributions of flow between mucosa and submucosa cannot therefore occur during stimulation of the sympathetic nerves or infusions of drugs such as noradrenaline or adrenaline.
. When microspheres are used in pharmacological investigations on distribution of blood flow in organs, controls to validate the method for the particular areas being studied are essential. If the vessels in the areas studied are in series rather than in parallel, the method is invalid.
The effects of dipyridamole on the myocardial vasodilator actions of noradrenaline, isoprenaline and adenosine
Authors: PARRATT J. R. , WADSWORTH R. M. 
Published: July 2012

Summary
. In anaesthetized cats, intravenous adenosine infusions decreased resistance to blood flow in the myocardial vascular bed. This effect of adenosine was augmented during the 60 min following the intravenous injection of dipyridamole (1 mg/kg).
. In different experiments, intravenous infusions of noradrenaline caused either a slight increase or a slight decrease in myocardial vascular resistance. The dilator component of the action of noradrenaline was not augmented by dipyridamole.
. Isoprenaline infusions decreased the resistance of the myocardial bed. This effect was unaltered after dipyridamole.
. These results do not support the hypothesis that part of the effect of catecholamines on myocardial vascular resistance involves the release of adenosine from hypoxic myocardial cells.
The hyperglycaemic effect of morphine
Authors: FELDBERG W. , SHALIGRAM S. V. 
Published: July 2012

Summary
. In the unanaesthetized cat, an injection of 0·75 mg of morphine into a lateral cerebral ventricle produced strong hyperglycaemia; on intravenous injection, 10 to 30 times larger doses were required. Other effects produced with both injections were shivering, pupillary dilatation, opening of the eyes, miaowing, periods of excitation, and analgesia. Between the periods of excitation the cat did not react to objects moving in front of its eyes and it had a vacant stare.
. Noradrenaline, adrenaline, and 5‐hydroxytryptamine (5‐HT) injected intraventricularly (250 μg, twice) depressed the hyperglycaemia due to intraventricular morphine, and noradrenaline also depressed the hyperglycaemia due to intravenous morphine. Adrenaline produced the strongest and 5‐HT the weakest depression. 5‐HT did not depress the other effects of morphine, but the catecholamines depressed most of them; only analgesia and the vacant stare appeared to be unaffected.
. Reserpine injected intraventricularly (0·5 mg, twice) greatly accentuated the hyperglycaemia as well as the other effects produced by intraventricular morphine, but pupillary dilatation and opening of the eyes no longer occurred; the protrusion of the nictitating membranes produced by the reserpine persisted.
. Pentobarbitone sodium injected intraperitoneally in an anaesthetizing dose practically abolished the morphine hyperglycaemia, but injected intraventricularly in a dose of a few milligrammes, it had a two fold effect: depression followed by enhancement of the morphine hyperglycaemia. The enhancement may be due to sensitization of the effect of the adrenaline released by morphine, since adrenaline hyperglycaemia was enhanced as well.
. Morphine did not seem to act on structures in the walls of either the lateral or third ventricle when producing its hyperglycaemic effect on intraventricular injection. The action may therefore be on more caudally situated parts of the neuro‐axis, on the central grey, on structures in the floor of the fourth ventricle or of the lateral recesses, or even on structures near the ventral surface of the brain stem.
The ring test: a quantitative method for assessing the ‘cataleptic’ effect of cannabis in mice
Authors: PERTWEE R. G. 
Published: July 2012

Summary
. A bioassay for cannabis, called the ring test, has been developed in which the percentage of the total time spent on a horizontal wire ring during which a mouse remains completely immobile is recorded.
. The effect of cannabis on mobility is a dose‐related, graded response.
. Threshold doses of cannabis extract are 12·5 mg/kg when injected intravenously, and 100 mg/kg when injected intraperitoneally or subcutaneously.
. The method provides a measure of the ‘cataleptic’ effect of cannabis. Chlorpromazine in doses of 1 mg/kg upwards also produces the effect but barbitone does not.
. It is concluded that Δ1‐tetrahydrocannabinol (Δ1‐THC) is largely responsible for the effect of cannabis extract on mobility; the potency ratio of Δ1‐THC to cannabis extract is between 10 and 20. Δ1‐Tetrahydrocannabidivarol (Δ1‐THD) also affects mobility but is less active than Δ1‐THC. Cannabidiol has no effect when injected intraperitoneally in doses up to 100 mg/kg.
Changes in body temperature produced by cholinomimetic substances injected into the cerebral ventricles of unanaesthetized cats
Authors: HALL G. H. 
Published: July 2012

Summary
The effects on body temperature of a number of substances injected into a lateral cerebral ventricle were examined in the unanaesthetized cat.
Nicotine (50 and 100 μg) caused a fall in body temperature ranging from 0·95–2·1° C associated with skin vasodilatation, tachypnoea and panting. These responses were prevented by the intraventricular injection of hexamethonium or mecamylamine, but not of atropine or phentolamine.
Carbachol (5 μg) caused a rise in temperature associated with skin vasoconstriction, piloerection and severe shivering. These effects were prevented by the intraventricular injection of atropine, but not of hexamethonium or mecamylamine.
An acetylcholine/eserine mixture (10 μg of each) had no reproducible effect on body temperature. Because of the variability in the response, interaction studies with antagonist drugs were not performed.
Hexamethonium (100 μg) or mecamylamine (100 μg) caused a prolonged rise in temperature, together with skin vasoconstriction, piloerection and intense shivering. Atropine (200 μg) was without effect on body temperature.
Noradrenaline (100 μg) caused a fall in temperature with skin vasodilatation. The fall was converted to a rise with skin vasoconstriction, piloerection and vigorous shivering following an intraventricular injection of phentolamine (100 μg).
These observations suggest the existence of cholinergic heat loss and heat gain mechanisms in the hypothalamic thermoregulatory pathways of the cat and the interaction studies with hexamethonium, mecamylamine and atropine, support the involvement of ‘nicotinic’ and ‘muscarinic’ receptors within the cholinergic thermoregulatory system.