bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE METABOLISM OF PROSTAGLANDINS BY THE GUINEA‐PIG UTERUS WITH PARTICULAR REFERENCE TO CORPUS LUTEAL MAINTENANCE IN EARLY PREGNANCY1
Authors: WALKER FELICITY M. MAULE , POYSER N.L. 
Published: July 2012

Homogenized lung tissue from day 15, pregnant and non‐pregnant guinea‐pig metabolized exogenous prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) almost completely when incubated in Tyrode solution containing β‐nicotinamide adenine dinucleotide (NAD+).
Metabolism of PGE2 and PGF2α by homogenates of day 15, pregnant or non‐pregnant, guinea‐pig uteri was relatively low (8 to 20%) when incubated in Tyrode solution containing NAD+.
Day 15, guinea‐pig conceptuses (placentae and embryos), homogenized and incubated in Tyrode solution containing NAD+, metabolized prostaglandins to a slightly greater extent (14 to 22%) than day 15, uterine tissue.
Addition of exogenous arachidonic acid to day 12 or day 15, pregnant, guinea‐pig uterine homogenates in Tyrode solution did not increase the yield of PGF2α following incubation.
It is concluded that neither an increase in metabolism of PGF2α by the uterus and conceptus nor lack of precursor is responsible for the lower secretion of PGF2α from the day 15, pregnant, guiena‐pig uterus when compared to the day 15, non‐pregnant uterus.
INITIAL INVESTIGATIONS INTO ADRENALINE ACCUMULATION AND ADRENERGIC RESPONSIVENESS IN CULTURED NEONATAL RAT HEART CELLS
Authors: WALKER M.J.A. 
Published: July 2012

Accumulation of tritiated adrenaline (and/or its products) has been studied by a variety of techniques in viable, attached and free‐floating myoblasts cultured from neonatal rat heart cells.
Accumulation increased with the number of cells used, the culture age of cells, incubation time and the concentration of adrenaline in the incubation mixture.
Accumulation‐concentration data were not linearly correlated with dose‐response data.
Accumulation did not correlate well with β‐adrenoceptor responsiveness in a number of situations of varying responsiveness.
Accumulation was not blocked by a variety of uptake blocking agents or α‐ and β‐adrenoceptor antagonists.
A much smaller accumulation process was observed in fibroblasts which respond to adrenaline with reversible morphological changes.
EFFECT OF PARATHYROIDECTOMY ON CARDIOVASCULAR REACTIVITY IN RATS WITH MINERALOCORTICOID‐INDUCED HYPERTENSION
Authors: BERTHELOT A. , GAIRARD A. 
Published: July 2012

Previous work has shown that parathyroidectomy protected Sprague‐Dawley rats against mineralocorticoid hypertension.
In order to explain this protection, we studied vascular reactivity to noradrenaline and angiotensin II in several groups of rats with and without their parathyroid and thyroid glands. Work was performed in vagotomized, anaesthetized rats after ganglionic blockade with pentolinium, and atropine sulphate.
The reactivity to noradrenaline was significantly lower in parathyroidectomized rats, especially at the beginning of mineralocorticoid treatment.
Autotransplantation of parathyroid glands in thyroparathyroidectomized rats re‐established normal cardiovascular reactivity and development of hypertension.
Cardiovascular reactivity to angiotensin II was not affected in parathyroidectomized rats and was lowered in thyroparathyroidectomized thyroxine‐treated rats.
5‐HYDROXYTRYPTAMINE AND DOPAMINE TRANSPORT BY RAT AND HUMAN BLOOD PLATELETS
Authors: GORDON J.L. , OLVERMAN H.J. 
Published: July 2012

Uptake of 5‐hydroxytryptamine (5‐HT) by rat platelets in plasma was very rapid and diffusion did not contribute significantly at substrate concentrations that did not saturate the active transport.
Under conditions which allowed measurement of initial rates of uptake, kinetic analysis revealed a high affinity uptake mechanism for 5‐HT (Km = 0.7 μM).
Uptake of dopamine was relatively slow and involved a lower affinity (Km = 70 μM) active transport process. Diffusion contributed significantly at concentrations that did not saturate the active transport.
5‐HT competitively inhibited uptake of dopamine, and vice versa; Ki values for both amines were similar to their respective Km values for uptake.
Chlorimipramine, desmethylimipramine and benztropine were tested as uptake inhibitors. Each was equipotent against 5‐HT and dopamine, although the absolute potency of the drugs varied greatly. Chlorimipramine was the most potent (Ki ≃ 100 nM), and kinetic analysis revealed that the inhibition was competitive against both 5‐HT and dopamine.
Similar results were obtained in studies with human platelets: Km values for 5‐HT and dopamine were about 1μM and 100 μM respectively. Activity profiles of inhibitors were also similar: each compound tested was equipotent against 5‐HT and dopamine, and the two amines each competitively inhibited uptake of the other.
We conclude that dopamine is actively transported by platelets via the 5‐HT uptake mechanism, but with a much lower affinity. There is no high‐affinity dopamine‐specific mechanism corresponding to that in the corpus striatum. Consequently although platelets may be valid models of transport in 5‐hydroxytryptaminergic neurones, they should not be regarded as models for the dopamine transport mechanism found in dopaminergic neurones.
RESPONSES OF THE PITUITARY‐ADRENAL SYSTEM OF THE PIG TO ENVIRONMENTAL CHANGES AND DRUGS
Authors: BLATCHFORD D. , HOLZBAUER MARGARETHE , INGRAM D.L. , SHARMAN D.F. 
Published: July 2012

The reactivity of the pituitary‐adrenal axis of the young pig was tested for its suitability as a sensitive index for any discomfort that might be experienced under certain conditions of intensive husbandry.
In a thermoneutral environment, most undisturbed piglets showed only slight variations in the plasma concentrations of adrenocorticotrophic hormone (ACTH) and corticosteroids.
Stimuli such as exposure to ambient temperatures of +40°C or −5°C were required to cause large rises in the plasma concentrations of ACTH and corticosteroids.
Apparently milder stimuli, such as change of environment, slight frustration or changes in ambient temperatures between +5°C and +30°C only rarely caused a significant rise in plasma corticosteroids. Thus changes in plasma corticosteroid concentrations are not a sensitive index for the reaction of a piglet to its environment.
Increases in plasma ACTH concentrations occurred faster than those of the corticosteroids, were larger when expressed as a percentage of the basal values and occurred following relatively small disturbances such as omission of the reward in an operant behaviour test when corticosteroid changes were often not detectable. Thus rises in plasma ACTH might be a useful indication that a given situation is disturbing to a pig. The reaction of plasma ACTH concentrations to chronic irritations as they might occur in intensive husbandry remains to be investigated.
Azaperone (2 mg/kg i.m.), a drug which is used as a sedative in pigs, caused a rise of about 50% in plasma corticosteroid concentrations. It did not diminish the large steroid output seen when the animals were exposed to high and low ambient temperatures.
THE ACTIONS OF DIAZEPAM AND PHENYTOIN ON A LOW DOSE PENICILLIN EPILEPTIFORM FOCUS IN THE ANAESTHETISED RAT
Authors: GARTSIDE I.B. 
Published: July 2012

A technique is described for the induction of an acute short‐lived epileptiform focus by the local injection of benzyl penicillin 25 units into the cerebral cortex of rats anaesthetized with urethane. The effects of anticonvulsants on this microfocus have been studied.
Phenytoin 20 mg/kg and diazepam 1 mg/kg intravenously significantly reduced the frequency of the normally occurring surface positive electrocorticogram (ECoG) plateaux and caused a greater decrease in the frequency of the epileptiform spikes normally associated with these plateaux.
A novel effect was seen in that both anticonvulsant drugs significantly reduced the amplitude of the epileptiform spike within the focus, as well as causing an even larger decrease in the amplitude of the propagated spike. The contribution of the anticonvulsant drug effect on the focal spike to its effect on propagated activity is discussed.
A STUDY OF THE SYMPATHOMIMETIC ACTION OF GUANETHIDINE ON THE ISOLATED ANOCOCCYGEUS MUSCLE OF THE RAT
Authors: FOSTER R.W. , SHAH D.S. , SMALL R.C. 
Published: July 2012

Guanethidine, acting on the rat isolated anococcygeus, causes adrenergic neurone blockade (slowly terminated by washing), noradrenaline potentiation and, with higher concentrations, spasm (both rapidly terminated by washing).
The spasm is an indirect sympathomimetic action, for it is sensitive to phentolamine and reserpine and shows tachyphylaxis.
The concentration of cocaine equieffective with the spasmogenic concentration of guanethidine as an inhibitor of noradrenaline uptake caused much less spasm. Moreover, it did not enhance noradrenaline efflux from anococcygeus loaded with (−)‐[3H]‐nor adrenaline, as guanethidine did.
The spasm induced by guanethidine in excess of cocaine is due to guanethidine‐evoked noradrenaline release.
THE ACTION OF BRADYKININ AND OXYTOCIN ON THE ISOLATED WHOLE UTERUS AND MYOMETRIUM OF THE RAT IN OESTRUS
Authors: WHALLEY E.T. 
Published: July 2012

A technique is described for obtaining a myometrial preparation devoid of endometrium, from the uterus of the rat in oestrus.
Acetylcholine and prostaglandin F2α (PGF2α) produced concentration‐effect curves with the same maximal tensions and slope on the whole uterus and myometrial preparations. Concentration‐effect curves to bradykinin and oxytocin on the myometrial preparation were altered, resulting in a shift to the right and a decreased maximum response compared with those produced by the whole uterus.
Indomethacin produced greater antagonism of the responses of the whole uterus to bradykinin and oxytocin than to acetylcholine and PGF2at, whereas responses of the myometrium to all four agonists were similarly depressed.
Responses of the myometrial preparation to a range of concentrations of bradykinin and oxytocin were significantly enhanced by prior sensitization of the myometrium to PGF2flt. This significant enhancing effect of PGF2flt was only seen with the threshold dose of acetylcholine.
It appears that the mechanism of action of bradykinin and oxytocin on the rat uterus involves both a direct action and an indirect action. The indirect action possibly involves release of prostaglandins) from the endometrium.
A NEW BIOASSAY FOR GLUCAGON
Authors: GAGNON G. , REGOLI D. , RIOUX F. 
Published: July 2012

The relaxant action of glucagon has been studied in strips of rabbit renal arteries partially contracted by a low concentration (1 ng/ml) of noradrenaline.
The preparation was relaxed in a dose‐dependent manner by concentrations of glucagon varying between 25 ng/ml and 420 ng/ml.
The relaxant effect of glucagon (0.1 μg/ml ≅ ED60) on this preparation was not affected by propranolol (5.0 μg/ml), cimetidine (10 μg/ml), diphenhydramine (10 μg/ml), indomethacin (5.0 μg/ml), phentolamine (1.2 μg/ml), atropine (10 μg/ml) and 8‐Leu‐ATII (1.0 ng/ml) but was slightly potentiated by Des‐Arg9 Leu‐OMe8‐Bk (25 μg/ml) and indomethacin (50 μg/ml).
The dose‐response curve to glucagon remained parallel in the presence of papaverine (2.5 μg/ml) but was shifted to the left by a factor of 2.5 to 2.8. Theophylline (250 μg/ml) also potentiated the vascular relaxation induced by glucagon.
Insulin (10 μg/ml) did not influence the relaxant effect of glucagon.
The removal of the N‐terminal amino acid (His) of glucagon reduced by 89% the biological activity of this fragment on the vascular preparation. The removal of the C‐terminal amino acids Met‐27, Asn‐28 and Thr‐29 of glucagon resulted in a fragment which was inactive either as an agonist or as an antagonist when tested at concentrations as high as 925 ng/ml.
It is concluded that the relaxation of partially contracted strips of rabbit renal arteries by glucagon constitutes a simple, sensitive, relatively specific and reliable bioassay which may be useful for the determination of glucagon in biological materials and for structure‐activity relationship studies with this hormone.
METABOLISM AND DISTRIBUTION OF EXOGENOUS HISTAMINE IN CATS
Authors: IMRIE P.R. , MARLEY E. , THOMAS D.V. 
Published: July 2012

The metabolism and disposition in blood and tissues of exogenous [14C]‐histamine was examined in cats.
The principal metabolites in blood of histamine instilled into the small intestine (directly or by transfer from the stomach) and colon were imidazoleacetic acid and t‐methylimidazoleacetic acid, being present in approximately equal amounts although in individual cats one or other acid could predominate. Only small amounts of histamine entered the circulation although in two of four cats given the largest dose (82 μmol/kg) large amounts were recovered. The amount of 14C radioactivity absorbed varied directly with the dose instilled. The chief metabolite in kidney and urine, whether histamine was instilled into the intestine or infused parenterally, was t‐methylimidazoleacetic acid. Histamine was not absorbed from the stomach and its metabolism there was negligible.
In contrast, when histamine was infused into blood leaving the intestine (portal vein) the main metabolite in blood and tissues was t‐methylimidazoleacetic acid being found in approximately 5‐fold the concentration of imidazoleacetic acid. The small amount of histamine which eluded inactivation/uptake by liver, lungs, heart during the infusion was halved on circulation through the intestine. When histamine was infused into blood supplying the intestine, (cranial mesenteric artery) t‐methylimidazoleacetic acid while still the major metabolite in blood was now only 1.4 times the concentration of imidazoleacetic acid. Additionally, the blood concentration of histamine during the infusion exceeded that of the metabolites.
t‐Methylimidazoleacetic acid was also the principal metabolite in blood and tissues following histamine infusion into a cannula carrying a replacement venous blood supply to the liver of abdominally eviscerated cats. Imidazoleacetic acid and t‐methylhistamine were present in equal concentrations and in one‐quarter to one‐third that of the methylated acid. The latter was also the principal metabolite following intra‐arterial histamine infusion to abdominally eviscerated cats without a hepatic blood supply, although initially tmethylhistamine predominated: a large peak of histamine was present during the infusion period. When additionally the renal vessels were ligated, tmethylhistamine predominated throughout the experiment.
In conclusion, intraduodenally instilled histamine was metabolized equally by diamine oxidase and imidazole N‐methyltransferase (followed by deamination by monoamine oxidase). In contrast, imidazole N‐methyltransferase was the principal inactivator of parenterally infused histamine, deamination of tmethylhistamine by monoamine oxidase becoming progressively less efficient with the cumulative exclusion of the intestines, liver and kidney from the circulation.
In vitro EFFECTS OF NON‐STEROIDAL ANTI‐INFLAMMATORY DRUGS ON HUMAN POLYMORPHONUCLEAR CELLS AND LYMPHOCYTE MIGRATION
Authors: BROWN K.A. , COLLINS A.J. 
Published: July 2012

The action of the non‐steroidal anti‐inflammatory drugs (NSAID), sodium salicylate, aspirin, phenylbutazone and indomethacin was investigated on the migration of human polymorphonuclear cells (PMNs) and lymphocytes, using the system of migration of leucocytes from glass capillary tubes.
All NSAID produced a dose‐dependent inhibition of cell migration, and were more effective on the migration of the PMN than on lymphocytes.
Drugs optimally suppressed PMN migration after 20 to 24 h incubation, and lymphocytes after
to 6 h.
Prolonged incubation of cells with several concentrations of NSAID demonstrated an ‘escape’ from inhibition in PMNs prepared from one subject.
ASPIRIN, PROTEIN TRANSACETYLATION AND INHIBITION OF PROSTAGLANDIN SYNTHETASE IN THE KIDNEY
Authors: CATERSON ROBYN J. , DUGGIN GEOFFREY G. , HORVATH JOHN , MOHANDAS JANARDANAN , TILLER DAVID 
Published: July 2012

The effect of aspirin on the kidney has been investigated in mice and rabbits. [Acetyl‐14C]‐aspirin was administered intraperitoneally in doses ranging from subtherapeutic to toxic. The degree of acetylation of protein was determined by the radioactivity remaining on protein precipitates of renal cortex and medulla after sequential washing designed to remove non‐covalently bound material. Controls were established, by the use of [carboxyl‐14C]‐aspirin.
The acetyl‐14C residue was bound to renal proteins in a linear manner in increasing amounts with increasing dosage up to 100 mg/kg. The [carboxyl‐14C]‐aspirin was not bound and thus the salicylate portion of the molecule was not bound covalently to the renal protein. The time course of the acetylation was rapid, consistent with the rate of aspirin absorption. The disappearance of acetylated protein was slow, with a Tl/2 of 112.5 h in the renal cortex, and 129.5 h in the renal medulla.
Differential centrifugation, Sephadex chromatography and gel electrophoresis were carried out on tissue homogenates to determine the site of acetylation. The acetylation was greatest in the microsomal fraction, although all protein fractions showed some degree of acetylation.
The prostaglandin synthetase activity of a particulate preparation from rabbit kidney was determined by a spectrophotometric assay of malondialdehyde formation. Aspirin (10 mg/kg, i.v.) significantly inhibited prostaglandin synthetase in the renal cortex and medulla.
Aspirin and renal proteins undergo a transacetylation reaction resulting in stable acetylated protein, with acetylation being greatest in the microsomal fraction. Aspirin has been shown to inhibit prostaglandin synthetase and this could lead to functional impairment of the tissue.
EFFECTS OF CALCIUM ON ACID SECRETION FROM THE RAT ISOLATED GASTRIC MUCOSA DURING STIMULATION WITH HISTAMINE, PENTAGASTRIN, METHACHOLINE AND DIBUTYRYL CYCLIC ADENOSINE‐3′,5′‐MONOPHOSPHATE
Authors: MAIN I.H.M. , PEARCE J.B. 
Published: July 2012

An isolated gastric mucosal preparation from immature rats is described. The mucosal surface was superfused and acid secretion was recorded continuously by monitoring H+‐ion concentration.
Repeated stimulation with submaximal concentrations of histamine or dibutyryl cyclic adenosine 3′,5′‐monophosphate (db cyclic AMP) produced consistent responses. Secretion induced by pentagas‐trin and methacholine demonstrated varying degrees of tachyphylaxis. All responses were readily reversed on washing out the secretagogue.
Reduction of Ca2+ from 3.6 mm increased responses to histamine, pentagastrin and methacholine while increase of Ca2+ to 7.2 mm decreased responses. Db cyclic AMP‐induced secretion was not influenced by external Ca2+.
When Mg2+ was raised from 1.2 mm responses to histamine and pentagastrin increased. Replacement of Ca2+ with Mg2+ produced a transient increase followed by a decrease in responses.
The similarity of the effects of Ca2+ on pentagastrin, methacholine and histamine indicates that neither pentagastrin nor methacholine act via Ca2+‐dependent histamine release.
ANTAGONISM BY CLONIDINE OF NEURONAL DEPRESSANT RESPONSES TO ADENOSINE, ADENOSINE‐5′‐MONOPHOSPHATE AND ADENOSINE TRIPHOSPHATE
Authors: STONE TREVOR W. , TAYLOR DAVID A. 
Published: July 2012

Adenosine and its nucleotides adenosine‐5′‐monophosphate (AMP) and adenosine triphosphate (ATP) have been applied by microiontophoresis to neurones in the cerebral cortex of rats anaesthetized with urethane. The firing rate of most neurones was depressed, though two cells were encountered which showed biphasic responses to ATP consisting of an initial excitation succeeded by depression.
The application of clonidine with iontophoretic currents of less than 25 nA resulted in blockade of the depressant responses to the purines, without affecting responses to noradrenaline, 5‐hydroxytryptamine or γ‐aminobutyric acid (GABA). At much higher doses of clonidine, direct depression of cell firing occurred and occasional interaction with noradrenaline was noted.
In the case of the biphasic responses to ATP, clonidine seemed to block only the depressant phase. Reduction of the excitatory component paralleled changes of background firing.
It is concluded that, in common with some other 2‐substituted imidazoline derivatives, clonidine possesses the ability to block responses to purine compounds.
DEPRESSION OF EVOKED POTENTIALS IN BRAIN SLICES BY ADENOSINE COMPOUNDS
Authors: SCHOLFIELD C.N. 
Published: July 2012

A study has been made of the action of adenosine on surface slices of guinea‐pig olfactory cortex in vitro.
With extracellular recordings from the pial surface and stimulation of the presynaptic input, the lateral olfactory tract (LOT) generated a monosynaptic negative wave representing dendritic excitatory potentials. This negative wave was depressed by bath application of 1 μm adenosine with increasing effect up to 1 mm. Adenosine 5′‐triphosphate (ATP), adenosine 5′‐monophosphate (AMP) and cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) had similar depressant actions. Adenine and guanosine were very weak depressants.
Theophylline concentrations in the range 10 μm to 3 mm progressively antagonized the action of adenosine.
Dibutyryl cyclic AMP (100 μm) and agents which increase intracellular cyclic AMP were not depressants, suggesting that the action of adenosine was not cyclic AMP‐mediated.
Intracellular recordings confirmed the depressant effect of adenosine on excitatory potentials generated by LOT stimulation and also showed that postsynaptic action potentials and the membrane of the soma were unaffected by adenosine.
Since presynaptic action potentials were also unaffected by adenosine, these experiments suggest that adenosine reduces excitatory transmission at LOT synapses and fortifies the idea that adenosine has a ‘neurohumoral’ action.
EFFECTS OF DROPERIDOL ON ACTIVITY OF CAROTID BODY CHEMORECEPTORS IN CAT
Authors: AMINOFF M.J. , JAFFE R.A. , SAMPSON S.R. , VIDRUK E.H. 
Published: July 2012

The effect of droperidol on the spontaneous activity of carotid body chemoreceptors and on their response to various stimuli was studied in 21 anaesthetized, paralyzed and artificially ventilated cats. Carotid body blood flow was controlled with a perfusion pump, and drugs were injected into the perfusion circuit.
In low doses, droperidol transiently increased the rate of spontaneous chemoreceptor activity, but in higher doses it depressed chemoreceptor activity after an initial stimulation.
Droperidol reduced or abolished the normal increase in chemoreceptor activity produced by stagnant asphyxia. This effect did not depend solely on the ability of droperidol to suppress spontaneously occurring impulses. Chemoreceptor responses to sodium cyanide, and to dopamine were also inhibited.
Dopamine antagonists other than droperidol were also studied for their effect on chemoreceptor activity. Chlorpromazine depressed spontaneous chemoreceptor activity and also reduced the chemoreceptor responses to sodium cyanide and dopamine, as did pimozide. The effects of these dopamine antagonists were much briefer and less marked than those of droperidol.
Although the influence that we have shown droperidol to have on peripheral chemoreceptor activity has an uncertain basis, it may have important implications in human and veterinary medicine.