bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECT OF SYMPATHOMIMETIC AMINES ON THE VENTRICULAR FIBRILLATION THRESHOLD IN THE RABBIT ISOLATED HEART
Authors: MURNAGHAN M.F. 
Published: July 2012

The ventricular fibrillation threshold (VFT) was measured in the isolated heart of the rabbit perfused via the aorta with McEwen's solution at 37° C by applying a single 10 ms pulse of current during the vulnerable period of late systole. The arrhythmia induced was either fibrillation or a rapid tachycardia.
The catecholamines adrenaline, noradrenaline and isoprenaline, but not dopamine, when infused at rates which produced similar moderate effects on cardiac rate and force, significantly lowered the VFT; it was reduced slightly more by adrenaline than by the other two. Phenylephrine and methoxamine were ineffective. Only those sympathomimetic amines which lowered the VFT also shortened the vulnerable time, i.e. minimal time after the R‐wave of the ECG at which the pulse had to be applied to induce the arrhythmia.
The lowering effect of adrenaline on the VFT was not influenced by phentolamine but was blocked by propranolol and pindolol.
Chloroform potentiated the lowering effect of adrenaline, but not that of isoprenaline, on the VFT. Carbachol did not alter the effect of adrenaline on the VFT.
The results indicate that adrenaline, noradrenaline and isoprenaline lower the VFT by a direct action on the cardiac musculature and that this effect is mediated via β‐adrenoceptors.
SOME CENTRAL EFFECTS OF 5‐HYDROXYTRYPTAMINE IN YOUNG CHICKENS AT AND BELOW THERMONEUTRALITY
Authors: MARLEY E. , WHELAN JENNIFER E. 
Published: July 2012

Three salts of 5‐hydroxytryptamine, the hydrogen maleinate, the oxalate and the creatinine sulphate were infused into the hypothalamus of 10‐18 day old chickens at ambient temperatures in and below the thermoneutral range. Body temperature was recorded and behaviour observed. Electrocortigrams were recorded in experiments in which 5‐hydroxytryptamine hydrogen maleinate was used. The effects of a monoamine oxidase inhibitor and methysergide on these responses were similarly studied.
At thermoneutrality (31° C) all 3 salts produced behavioural sleep. 5‐Hydroxytryptamine oxalate had inconsistent effects on body temperature. 5‐Hydroxytryptamine creatinine sulphate produced hypothermia at small doses and mild hyperthermia at higher doses. 5‐Hydroxytryptamine hydrogen maleinate produced hypothermia at all doses tested; the falls in temperature induced by this salt were intensified in magnitude and duration by monoamine oxidase inhibition unlike the responses to the other 2 salts.
At temperatures below thermoneutrality (16° C) all 3 salts produced behavioural sleep and electrocortical sleep was recorded with 5‐hydroxytryptamine hydrogen maleinate. All 3 salts produced hypothermia, which was intensified in magnitude and duration by monoamine oxidase inhibition.
The hypothermia produced by 5‐hydroxytryptamine hydrogen maleinate was prevented by equimolar doses of methysergide.
The position of the cannula in the hypothalamus was found to be crucial.
The results contrast with those found in the adult fowl. No conclusion is drawn as to the relationships of the actions of these salts when infused compared with the effects of endogenous 5‐hydroxytryptamine release.
INFLUENCE OF HISTAIMINE H1 AND H2‐RECEPTOR BLOCKERS ON SYMPATHETIC VASODILATOR AND VASOCONSTRICTOR RESPONSES IN CANINE PAW
Authors: KRAFT E. , ZIMMERMAN B.G. 
Published: July 2012

Vasodilator responses to histamine, bradykinin and sympathetic nerve stimulation were elicited in the perfused paw of dogs treated with bretylium (15‐20 mg/kg) and atropine. The H2‐receptor blocking agent, burimamide, when administered in the dose of 5 mg/kg intravenously and 4 mg intra‐arterially did not depress significantly these vasodilator responses. The subsequent administration of tripelennamine in the dose of 2.5‐5 mg/kg intravenously and 4 mg intra‐arterially produced a significant blockade of the response to histamine and reduced the sustained vasodilator response to nerve stimulation.
In guanethidine‐treated dogs, tripelennamine administered in the same dose following burimamide produced a blockade of the respone to histamine comparable to that in the bretylium experiments, but decreased only the sustained vasodilator response to stimulation at 1 Hz. When the order of administration of the antihistamines was reversed in another group of guanethidine‐treated dogs, tripelennamine had only a slight blocking effect on the response to histamine and did not affect the responses to nerve stimulation. Burimamide exerted a significant blocking effect on the response to histamine, but not to nerve stimulation. Another H2‐receptor blocking agent, metiamide, when given after tripelennamine, also had a marked blocking effect on the response to histamine and almost abolished the vasodilator response to 4‐methylhistamine, an H2‐agonist. Nevertheless, even in the presence of this profound histamine blockade, the sustained vasodilator response to nerve stimulation remained unchanged.
In another group of experiments vasoconstrictor responses to exogenous noradrenaline and sympathetic stimulation were initially depressed by burimamide and later returned to control values. Tripelennamine increased these responses by its uptake blocking action.
It is concluded that the sustained vasodilator response is not antagonized by a specific antihistaminic action. The decrease in the sustained vasodilator response produced by antihistamines is probably attributable to potentiation of a residual adrenergic vasoconstrictor effect not completely blocked by bretylium.
A FURTHER INVESTIGATION INTO THE ENERGY DEPENDENCE OF ANGIOTENSIN II‐INDUCED CONTRACTIONS OF ISOLATED SMOOTH MUSCLE PREPARATIONS
Authors: CROCKER ANN D. , WILSON K.A. 
Published: July 2012

The energy dependence of angiotensin and acetylcholine‐induced contractions of rat descending colon and uterus was investigated.
Differences were observed in the effect of anaerobic substrate depletion upon responses of colon and oestrous and dioestrous uterus. These were attributed to differences in the energy metabolism of the tissues and were correlated with differences in tissue levels of glycogen.
The preferential reduction of angiotensin responses of dioestrous uterus and descending colon when exposed to 2,4‐dinitrophenol, was evidence for an energy dependent stage in the angiotensin response distinct from the contraction process itself.
The absence of a preferential reduction of the angiotensin response of oestrous uterus when exposed to 2,4‐dinitrophenol appeared to be related to the ability of this tissue to generate ATP by anaerobic glycolysis.
It was concluded that the energy for the angiotensin response may be derived either anaerobically or aerobically, depending upon the tissue.
EVIDENCE THAT ADRENERGIC NERVES ARE RESPONSIBLE FOR THE ACTIVE UPTAKE OF NORADRENALINE IN THE GUINEA‐PIG ISOLATED TRACHEA
Authors: FOSTER R.W. , O'DONNELL STELLA R. 
Published: July 2012

6‐Hydroxydopamine (50 mg/kg, i.p.) was given to guinea‐pigs to destroy the adrenergic nerve terminals in the trachea.
The destruction was demonstrated by fluorescence histochemistry, which showed a marked loss of beaded fluorescent terminal fibres and by electrical transmural stimulation of the isolated atropinized trachea, which showed a marked reduction of dilator responses.
Such tracheae showed greatly reduced uptake‐with‐retention of (—)‐[3 H]‐noradrenaline in incubation experiments and the efflux curve of radioactive material showed a selective but incomplete reduction in the volume of the slowly exchanging compartment.
It is concluded that much, but perhaps not all, of the uptake‐with‐retention occurs into adrenergic nerves.
ACTIVATION OF HISTIDINE DECARBOXYLASE BY H2‐RECEPTOR BLOCKADE: MECHANISM OF ACTION
Authors: HÅKANSON R. , HEDENBRO J. , LIEDBERG G. , REHFELD J.F. , STADIL F. 
Published: July 2012

Treatment with histamine H2‐receptor antagonists, which inhibit basal acid secretion, was found to activate rat stomach histidine decarboxylase. At the same time the serum gastrin concentration was greatly increased.
In antrectomized rats neither the enzyme activity nor the serum gastrin concentration was affected by the treatment.
In analogy with previous observations on other inhibitors of acid secretion we suggest that the H2‐receptor antagonists stimulate gastrin release through their effect on acid secretion and that the raised serum gastrin level is responsible for the enzyme activation.
AN ANALYSIS OF THE PHENOMENON OF ACUTE TOLERANCE TO MORPHINE IN THE GUINEA‐PIG ISOLATED ILEUM
Authors: KOSTERLITZ H.W. , WATERFIELD ANGELA A. 
Published: July 2012

The observations which Paton (1957) interpreted as ‘acute tolerance’ and ‘dependence’ have been confirmed for coaxially stimulated segments of guinea‐pig ileum and extended to the contractions evoked by field stimulation in the myenteric plexus‐longitudinal muscle preparation. Evidence is adduced that the morphine receptors of the myenteric plexus are not involved in the two phenomena.
The contraction of the longitudinal muscle depressed by low concentrations of morphine, or levorphanol, can be restored to control level not only by high concentrations of morphine but also by levorphanol and equally well by its (+)‐isomer, dextrorphan, which does not fulfil the stereospecific requirements of the morphine receptor. Acetylcholine output was not increased.
When, after restoration of the twitch by high concentrations of morphine, the drug is washed out, contractions become depressed. This effect cannot be due to ‘dependence’ because either morphine or its antagonist, naloxone, restore the twitch again.
In the concentrations used, morphine, levorphanol and dextrorphan inhibit the Cholinesterase of homogenates of the myenteric plexus‐longitudinal muscle preparation by 10‐15%, Since a concentration of physostigmine which causes a similar inhibition also restores the twitch, it is concluded that the described phenomena are best explained by the anticholinesterase effects of the drugs.
INDOMETHACIN, KETOPROFEN AND CORPUS LUTEUM REGRESSION IN THE GUINEA‐PIG
Authors: DONOVAN B.T. 
Published: July 2012

The accelerated regression of the corpora lutea normally produced by glass beads inserted unilaterally into the uterus of the guinea‐pig early in the oestrous cycle was prevented when the beads were filled with indomethacin or ketoprofen.
Luteal regression was enhanced by the placement of beads in both horns of the uterus. When empty beads were placed in one horn of the uterus and drug‐filled beads in the other, indomethacin blocked regression in both ovaries whereas ketoprofen was ineffective.
Indomethacin probably blocks luteal regression by inhibition of prostaglandin synthesis in the uterus.
SYNTHESIS OF KALLIKREINS BY RAT KIDNEY SLICES
Authors: NUSTAD K. , VAAJE KIRSTEN , PIERCE J.V. 
Published: July 2012

Four radioactive kallikreins were isolated from rat kidney slices incubated with [3 H]‐L‐leucine.
The kallikreins were purified by procedures previously used for the isolation of rat urinary kallikreins (Nustad & Pierce, 1974), and by affinity chromatography on a column of insolubilized anti‐rat urinary kallikrein.
The kidney kallikreins resembled the urinary kallikreins in their relative amounts, isoelectric points and electrophoretic mobilities on polyacrylamide disc gels.
The data indicate that the kidney synthesizes four kallikreins which are released into urine. The kallikreins are not changed by passage through the lower urinary tract.
THE DISTRIBUTION OF LITHIUM, SODIUM AND MAGNESIUM IN RAT BRAIN AND PLASMA AFTER VARIOUS PERIODS OF ADMINISTRATION OF LITHIUM IN THE DIET
Authors: BOND P.A. , BROOKS B.A. , JUDD A. 
Published: July 2012

The tissue solubilizer Soluene‐100 provides an efficient and easy means of preparing small amounts of rat tissue for cation analysis.
Administration of lithium ions to rats for two days to 42 days by the addition of lithium chloride to the diet at a concentration of 30 mmol/kg dry weight results in (a) the uniform distribution of lithium throughout the brain at a concentration comparable to that found in plasma; (b) decrease in the brain sodium concentration; (c) a decrease in brain magnesium concentration and an increase in plasma magnesium concentration; (d) no change in brain water content.
The inclusion of LiCl in the diet at a concentration of 30 mmol/kg dry food gives consistent and predictable plasma and brain levels of lithium in the rat without the occurrence of serious side effects over periods of up to 42 days.
DISCRIMINATION OF MONOAMINE UPTAKE BY MEMBRANES OF ADRENAL CHROMAFFIN GRANULES
Authors: DA PRADA M. , OBRIST R. , PLETSCHER A. 
Published: July 2012

The accumulation of various radioactive monoamines by isolated membranes of bovine adrenal chromaffin granules was measured by equilibrium dialysis.
Adenosine‐5′‐triphosphate (ATP) in the presence of Mg++ stimulated the uptake of all the amines tested, but the accumulation of dopamine, (‐)‐noradrenaline (NA), 5‐hydroxytryptamine (5‐HT), (±)‐adrenaline and (±)‐octopamine was greater than that of tyramine, (±)‐metaraminol, tryptamine, β‐phenylethy lamine and histamine.
At the higher concentration levels of the amines in the medium the ATP‐dependent accumulation of dopamine, NA, adrenaline and 5‐HT in the membranes reached a saturation level, whereas in the absence of the nucleotide no saturation level was attained.
Octopamine and 5‐HT competitively inhibited the ATP‐dependent uptake of NA.
Decrease in the incubation temperature or the presence of N‐ethylmaleimide greatly reduced the ATP‐stimulated amine accumulation. Ouabain had no effect on uptake.
Reserpine virtually abolished the ATP‐dependent uptake of dopamine, NA and 5‐HT, caused a partial inhibition of the metaraminol, octopamine and tyramine accumulation, but did not interfere with the uptake of tryptamine.
The content of endogenous catecholamines of the membranes was changed very little by incubation of NA and 5‐HT in the presence of ATP. However, the membranes lost over 80% of their endogenous amines if incubated for 30 min without ATP.
The ATP content of the medium progressively decreased during the incubation of granular membranes.
It is concluded that the membrane of adrenal chromaffin granules discriminates between the various monoamines with regard to the magnitude of their uptake and that two mechanisms of ATP‐stimulated uptake, one responsive and the other resistant to reserpine, exist at the level of this membrane. The ATP‐stimulated transport at the granular membrane level may be an important factor in determining the intraneuronal storage of a physiological or false neurotransmitter.
ROLE OF EXTRANEURONAL MECHANISMS IN THE TERMINATION OF CONTRACTILE RESPONSES TO AMINES IN VASCULAR TISSUE
Authors: KALSNER S. 
Published: July 2012

The role of the uptake and release of agonist from extraneuronal sites in the termination of responses of rabbit aortic strips to amines was studied.
Strips were contracted with adrenaline or noradrenaline and after a response plateau was reached, the muscle chambers were washed free of agonist and the relaxation in Krebs solution recorded. After inhibition of catechol‐O‐methyl‐transferase, monoamine oxidase and neuronal uptake the relaxation rate was greatly prolonged. Evidence is provided that this very slow relaxation resulted from the accumulation of intact amine at extraneuronal sites during exposure to the agonist and its subsequent release past receptors due to a reversal of the concentration gradient after washout.
Pretreatment with the haloalkylamine, GD‐131 (N‐cyclohexylmethyl‐N‐ethyl‐β‐chloroethylamine), an inhibitor of extraneuronal uptake, returned the slow relaxation rate after enzyme inhibition towards that of control strips. By blocking the extraneuronal transport of amines their accumulation at intracellular loci after enzyme inhibition was prevented.
The effects of GD‐131 and 17β‐oestradiol on the relaxation rate of untreated strips contracted by adrenaline and noradrenaline confirmed that extraneuronal uptake to sites of enzymatic activity is the major mechanism terminating their action.
Inactivation of extraneuronal transport sites by GD‐131 was prevented by protecting them with 17β‐oestradiol or normetanephrine during exposure to the haloalkylamine, pointing to a common site of action of these agents on a specific carrier system for amines.
Evidence is presented that the relaxation from contractions induced by histamine and 5‐hydroxytryptamine also involves extraneuronal accumulation and release, probably by an uptake process which is identical to the one for catecholamines.
STUDIES ON THE HYPOTENSIVE ACTION OF α‐METHYLDOPAMINE
Authors: FINCH L. , HERSOM A. , HICKS P. 
Published: July 2012

Intraventricular α‐methyldopamine (50–200 μg) produced a dose‐related fall in blood pressure in conscious spontaneously hypertensive rats. Pretreatment with intraventricular 6‐hydroxydopamine prevented this hypotensive effect of α‐methyldopamine.
The hypotensive effect of α‐methyldopamine was prevented by intraventricular injection of phentolamine or desmethylimipramine, but not by intraperitoneal injection of haloperidol.
Pretreatment with U‐14,624, a selective central dopamine‐β‐hydroxylase inhibitor, prevented the hypotensive effect of α‐methyldopamine.
α‐Methyldopamine was considerably less potent than noradrenaline as a pressor agent in the pithed rat, but noradrenaline and α‐methylnoradrenaline were found to be equipotent.
α‐Methyldopamine (1–5 mg i.c.v.) reduced pressor responses elicited by electrical stimulation of the mid brain reticular formation in cats anaesthetized with chloralose.
It is concluded that the hypotensive action of α‐methyldopamine in conscious animals involves intact central α‐adrenergic neurones and a central adrenergic uptake mechanism for the formation of α‐methylnoradrenaline.
HYPOTHERMIC EFFECT OF SODIUM ACETYLSALICYLATE ON AFEBRILE MONKEYS
Authors: CHAI C.Y. , LIN M.T. 
Published: July 2012

Afebrile monkeys (Macaca cyclopis) receiving systemic (100–300 mg/kg, i.p.) or central (5–20 mg into the 3rd cerebral ventricle) administration of sodium acetylsalicylate showed a dose‐dependent reduction in rectal temperature in a thermoneutral environment (25° C).
Administration of sodium acetylsalicylate (10 mg) into the 3rd cerebral ventricle produced a hypothermia with a temperature decrement of 1.0° C, while an intraperitoneal injection of 300 mg/kg was required for a temperature decrement of 0.9° C. The ratio between the total doses given by the two routes was 1 to 120.
Following the administration of sodium acetylsalicylate, a decline in rectal temperature was accompanied by a tail cutaneous vasodilatation.
The data suggest that sodium acetylsalicylate can lower the normal body temperature by activating heat loss or decreasing the normal (tonic) inhibition of the heat loss mechanism via the central nervous system.
RAT SUBMANDIBULAR GLAND KALLIKREINS: PURIFICATION AND CELLULAR LOCALIZATION
Authors: BRANDTZAEG P. , GAUTVIK K.M. , NUSTAD K. , PIERCE J.V. 
Published: July 2012

Four submandibular gland kallikreins (E.C. 3.4.21.8) were isolated by chromatography on DEAE‐Sephadex A‐50 and hydroxyapatite, followed by gel filtration and electrofocusing. The pI values were 3.87, 3.96, 4.07 and 4.16, and a common molecular weight of 34,000 was found.
The kallikreins were localized by direct immunofluorescence with an antibody to rat urinary kallikrein, to the granular tubules, striated duct cells and some main duct cells in the submandibular gland, and to striated duct cells in the sublingual gland. Kallikrein was not found in acini and stroma.
Several non‐kallikrein esterases present in the submandibular gland reacted with the antibody to rat urinary kallikrein. The antibody was made monospecific for kallikrein by absorption with the crossreacting esterases.
We suggest that kallikrein is produced in striated duct cells. Granular tubules, which are differentiated from striated duct cells, have preserved the ability to produce kallikrein. These cells also store large quantities of kallikrein.
THE EVALUATION OF THE NOVEL PRESSOR ACTIVITY OF γ‐PIPERIDINOBUTYRAMIDE (WY 20051, DF480)
Authors: ALPS B.J. , DEVOY P.W. , WATERFALL J.F. 
Published: July 2012

γ‐Piperidinobutyramide (Wy 20051, DF480) injected intravenously evoked pressor responses in the anaesthetized ganglion blocked rat preparation over the dose range 2.4 × 10−6‐3.0 × 10−4 mol/kg.
High doses (>3.8 × 10−5 mol/kg) or even repeated submaximal doses (1.9 × 10−5 mol/kg) of Wy 20051 caused tachyphylaxis of this pressor response.
The noradrenaline pressor‐response curve was shifted significantly to the right of the control curve following a dose of Wy 20051 (1.5 × 10−4 mol/kg cumulative).
The dose‐response curve for the pressor action of Wy 20051 was potentiated in reserpine‐treated anaesthetized rats. In contrast, tyramine‐induced pressor responses were abolished.
Wy 20051 contracted the guinea‐pig isolated aortic spiral preparation (3.8 × 10−5‐6.0 × 10−4 mol) and evoked constrictor responses in the perfused mesenteric vasculature preparation of the rat (5.9 × 10−7‐1.2 × 10−5 mol). At higher doses the responses were reduced.
Wy 20051‐induced constrictor responses of the perfused mesentery were unaffected by blockade of α‐adrenoceptors or by tachyphylaxis of 5‐hydroxytryptamine receptors.
The time for abolition of Wy 20051‐induced constrictor responses of the mesentery in a calcium‐free medium was not significantly different from that required for noradrenaline, but was significantly greater than that for KCl (P < 0.001).
Wy 20051 and noradrenaline, but not KCl, evoked constrictor responses in the depolarized rat mesenteric vasculature.
The results indicate that Wy 20051 evokes pressor responses which have some of the characteristics of those of noradrenaline. However, the responses are not elicited by an α‐adrenoceptor mechanism.
HYPOTHALAMO‐PITUITARY ADRENOCORTICAL FUNCTION IN THE RAT AFTER TREATMENT WITH BETAMETHASONE
Authors: BUCKINGHAM JULIA C. , HODGES J.R. 
Published: July 2012

Hypothalamo‐pituitary‐adrenocortical (HPA) activity was suppressed in rats treated with betamethasone.
Recovery of normal HPA function occurred after corticosteroid withdrawal.
Although corticotrophin release was rapidly restored to its basal rate there was a delay in the return of the normal adrenocorticotrophic response to stress and normal adrenocortical function was evident only after the plasma adrenocorticotrophic hormone had reached ‘supra‐normal’ levels.
The physiological significance and possible clinical relevance of the results are discussed.
ON THE MECHANISM OF ACTION OF CLOZAPINE ON THE ADRENERGIC NEURONE
Authors: DORRIS R.L. , SHORE P.A. 
Published: July 2012

The antipsychotic drug, clozapine, lowered noradrenaline and metaraminol (MA) concentrations in the rat heart. This action was blocked by the presence of a ganglionic blocking drug.
Other α‐adrenoceptor blocking drugs (phenoxybenzamine, phentolamine) did not significantly lower heart amine concentrations. An inhibitor of neuronal amine uptake (desipramine) caused only a slight lowering. The combination of phentolamine and desipramine showed considerable activity, and this action was blocked by ganglionic blockade.
Clozapine had little or no action in blocking amine uptake, yet greatly potentiated amine release caused by the phentolamine‐desipramine combination.
Other antipsychotic drugs (haloperidol, chlorpromazine, thioridazine) or other agents (propranolol, atropine) did not share this action of clozapine.
Ganglionic blockade markedly delayed amine release induced by reserpine administration.
It is suggested that clozapine may have an incomplete reserpine‐like effect specifically on the adrenergic neurone, facilitating impulse‐induced amine release.