bluuebunny/crossref_metadata_2025_split huggingface dataset:
ESTIMATION OF pKB VALUES FOR HISTAMINE H2‐RECEPTOR ANTAGONISTS USING AN in vitro ACID SECRETION ASSAY
Authors: ANGUS J.A. , BLACK J.W. , STONE M. 
Published: July 2012

Histamine H2‐receptor antagonism by burimamide, metiamide and cimetidine was analysed under apparent equilibrium conditions in the lumen‐perfused isolated stomach preparation of the mouse.
The behaviour of these compounds was not incompatible with simple competitive antagonism but the estimated pKB values (−log KB) were all significantly lower, by about 1 log unit, than reference values reported for guinea‐pig atrium or rat uterus.
There seems no need to propose that the parietal cell receptors are somehow different from the others; metiamide continually appears in the gastric juice so that a steady‐state but not equilibrium can presumably be reached with respect to the bath concentration and this could keep the antagonist concentration artificially low in the region of the receptors.
PARASYMPATHOMIMETIC INFLUENCE OF CARBACHOL ON LOCAL CEREBRAL BLOOD FLOW IN THE RABBIT BY A DIRECT VASODILATOR ACTION AND AN INHIBITION OF THE SYMPATHETIC‐MEDIATED VASOCONSTRICTION
Authors: AUBINEAU PIERRE , SERCOMBE RICHARD , SEYLAZ JACQUES 
Published: July 2012

Two sorts of effect of carbachol on local cerebral blood flow (caudate nucleus) have been studied: (a) a direct action on the arterial smooth muscle; (b) an interaction with the adrenergic (sympathetic) constrictor system which innervates the vascular system of this nucleus.
Continuous measurements of the following variables were performed in lightly anaesthetized rabbits: local blood flow (caudate nucleus), arterial blood pressure, PaO2, PaCO2.
After blockade of the nicotinic synapses in the superior cervical sympathetic ganglion by local hexamethonium injection, carbachol was infused into the common carotid artery, thus minimizing systemic effects of this drug. Infusions of 0.6, 1.3 and 2.5 μg kg−1 min−1 induced mean increases in caudate blood flow of about 8, 17 and 37% respectively, without notable modifications of other variables measured.
The dilator effect of 2.5 μg kg−1 min−1 carbachol was reduced to a mean of 12% after intravenous injection of 0.5 mg/kg atropine, and could be totally abolished by higher doses (1 to 1.5 mg/kg).
Administration of 2.5 μg kg−1 min−1 of carbachol diminished by more than 50% the reduction in caudate blood flow induced by postganglionic stimulation of the cervical sympathetic chain, but did not affect the reduction of flow obtained by intravenous infusion of noradrenaline (2.5 to 5.0 μg kg−1 min−1). This inhibition of the adrenergic (sympathetic) system by carbachol was not modified by high doses of atropine (1 mg/kg i.v.).
We conclude that: (a) the local cerebral blood flow of a deep structure can be significantly modified by activation of vascular muscarinic receptors; (b) activation of non‐muscarinic prejunctional cholinoceptors can cause inhibition of the sympathetic fibres innervating the vascular bed of the same structure.
EFFECTS OF DOPAMINE ON ADRENERGIC NEUROMUSCULAR TRANSMISSION IN THE GUINEA‐PIG VAS DEFERENS
Authors: BELL G. 
Published: July 2012

In the isolated vas deferens of the guinea‐pig, contractile responses to adrenergic nerve stimulation at 2 Hz were depressed by exogenous dopamine (5 μm) and this effect was abolished in the presence of phentolamine (0.3 μm), suggesting that it was due to an agonist action of dopamine on α‐adrenotors.The depression by dopamine (5 μm) of contractile responses to nerve stimulation was correlated with reduction in amplitude of single excitatory junction potentials (e.j.ps) evoked by nerve stimulation, but not with depression of spontaneous junction potentials.By contrast, during repetitive nerve stimulation at 1 Hz the depressant effect of dopamine on e.j.p. amplitude became less pronounced, due to the amount of facilitation being greater than that occurring under control conditions in the same cell.The α‐adrenoceptor antagonist, phentolamine (10 μm), also increased the amount of facilitation during repetitive nerve stimulation.In the presence of phentolamine (10 μm), the depressant effect of dopamine (5 μm) on single e.j.ps was abolished but its enhancing effect on facilitation was not reduced.It is suggested that the enhancement of facilitation during repetitive stimulation by both dopamine and phentolamine is independent of their actions on presynaptic α‐adrenoceptors.
ATTENUATED DEPRESSOR RESPONSE TO ARACHIDONIC ACID AND PROSTAGLANDINS IN UNCLIPPED RENAL HYPERTENSIVE RATS
Authors: TEN BERG R.G.M. , DE JONG W. , NIJKAMP F.P. 
Published: July 2012

In renal hypertensive rats (one‐clip, two‐kidney type) blood pressure returned to a normotensive level within 24 h after the removal of the renal artery clip (unclipping).
The decrease in blood pressure caused by intravenous administration of arachidonic acid, prostaglandin E2 and prostaglandin I2 was significantly reduced in these unclipped rats.
The hypotensive response to bradykinin and acetylcholine was the same in unclipped rats and in control rats.
Nephrectomy abolished the difference in blood pressure response to arachidonic acid and the two prostaglandins between unclipped and control rats.
An enhanced secretion of renin, as indicated by the absence of an increase in plasma renin activity, did not seem to be involved in the attenuated blood pressure response to arachidonic acid in unclipped rats.
INHIBITORY EFFECT OF ADENOSINE AND ADENINE NUCLEOTIDES ON POTASSIUM‐EVOKED EFFLUX OF [3H]‐NORADRENALINE FROM THE RAT ISOLATED HEART: LACK OF RELATIONSHIP TO PROSTAGLANDINS
Authors: KHAN MOHAMMAD T. , MALIK KAFAIT U. 
Published: July 2012

In the isolated heart of the rat prelabelled with [3H]‐noradrenaline (NA) and perfused with Krebs solution, administration of potassium (K+ 60 μmol) increased the efflux of total radioactivity and of [3H]‐NA in the perfusate.
Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine, but not inosine, dibutyryl cyclic adenosine 3′5′‐monophosphate (db cyclic AMP) or db cyclic GMP reduced the K+‐evoked overflow of total radioactivity and of intact [3H]‐NA, in concentrations too low to cause release of prostaglandins. ATP, ADP and adenosine did not affect tyramine‐evoked overflow of tritium.
Blockade of prostaglandin synthesis with indomethacin did not alter the inhibitory effect of either ATP, ADP or adenosine on K+‐induced overflow of tritium, thereby indicating that these nucleotides inhibit adrenergic transmission by a mechanism unrelated to stimulation of prostaglandin synthesis.
Theophylline which increases entry of calcium (Ca2+) across the cell membrane and reduces its binding in the cell, enhanced K+‐evoked overflow of tritium and diminished the inhibitory effect of ATP, ADP and adenosine on K+‐evoked overflow of tritium from the heart, presumably by interfering with transneuronal Ca2+ metabolism.
DIFFERENTIAL EFFECTS OF PROSTAGLANDINS ON CANINE INTRAPULMONARY ARTERIES AND VEINS
Authors: ALTURA BURTON M. , CHAND NARESH 
Published: July 2012

The sensitivity and contractility of isolated canine intrapulmonary arteries and veins to a variety of primary prostaglandin compounds was studied.
Intrapulmonary arteries produced no measurable contractile responses to prostaglandin A1 (PGA,), PGA2, PGB1, PGD2, PGE,1, PGE2 or to PGFlα. However, high concentrations of both PGB2 (> 10−7 m) and PGF2α (> 10−6 m) elicited concentrated‐related, but weak, contractile responses, measuring only 5–25% of KCl‐induced maximum contractions.
Intrapulmonary arteries, partially contracted by 5‐hydroxytryptamine (5‐HT), exhibited concentration‐related relaxations in response to PGE,1 PGE2, PGA1, or PGA2 produced only weak superimposed contrtactions.
In contrast to intrapulmonary arteries, intrapulmonary veins contracted in a concentration‐related fashion to all prostaglandins tested, where the contractile sensitivity was (based on EC50 s and threshold concentrations): PGB2 > PGB1, > PGD2 > PGF2α > PGA2 »PGA1, > PGF1α > PGE2 > PGE1.
In terms of the ability to generate maximum contractile responses on intrapulmonary veins, the prostaglandins were also variable, with PGA2 and PGB2 being the most potent and PGD2 the least potent.
Intrapulmonary veins, partially contracted by 5‐HT, exhibited concentration‐related relaxations to PGE1 at low concentrations, followed by secondary contractile responses at higher concentrations.
Neither PGA1 nor PGA2 (3.4 × 10−8 to 3.4 × 10−5 m) inhibited or potentiated 5‐HT responses of intrapulmonary arteries.
These data suggest that there are species, regional and major qualitative and quantitative, differences in the responsiveness of intrapulmonary arteries and veins to prostaglandin.
ATROPINE AND MICTURITION RESPONSES BY RATS WITH INTACT AND PARTIALLY INNERVATED BLADDER
Authors: CARPENTER F.G. 
Published: July 2012

Micturition responses by a group of 17 rats were recorded during a water diuresis. During a 2 h period, uniform volumes of urine were passed at regular intervals; the mean of the voiding responses by each animal was consistent from one water loading period to another. Residual urine volumes were physiologically insignificant.
Atropine treatment did not compromise seriously micturition by water‐loaded rats. Treated animals micturated more frequently; the mean volume was 68% of control. The residual urine volume was equal to that of controls.
Several weeks after the surgical removal of half the motor innervation of the bladder, there was no significant effect on micturition. Mean voiding volumes were not different from those of controls; residual urine volumes were the same as before denervation.
After half the innervation of the bladder had been destroyed, the effect of atropine on micturition was enhanced. Volumes passed were 50% of control; large residual volumes remained when micturition was over. Only in this group could bladder distension be found.
It is concluded that functional responses of the rat urinary bladder are not only resistant to atropine but also to the sizeable reduction in the number of neuroeffector units in the bladder itself. The functional reserve of the rat bladder musculature is remarkably high when assessed by its ability to empty adequately.
ISOPRENALINE‐ AND NORADRENALINE‐INDUCED HYPER‐POLARIZATION OF GUINEA‐PIG LIVER CELLS
Authors: KARASHIMA TSUYOSHI 
Published: July 2012

Effects of pretreatment with isoprenaline (Isop) or noradrenaline (NA) and various ionic environments on the NA‐induced or Isop‐induced hyperpolarization of guinea‐pig liver cells were investigated by means of a microelectrode technique.
NA (5.9 × 10−6 m) decreased the membrane resistance, and hyperpolarized the membrane with or without generation of an initial transient small depolarization. The NA‐induced initial depolarization was not dependent on the membrane potential and was increased by Isop (4.0 × 10−6 m) or glucagon (10−7m).
In Ca‐free solution, the NA‐induced hyperpolarization became transient and a continuous depolarization followed in the presence of NA. Repetitive application of NA resulted in a complete disappearance of the NA‐induced hyperpolarization and was replaced by a slowly developing depolarization with or without generation of the initial transient depolarization. In excess [Ca]0, the NA or Isop‐induced hyperpolarization was increased.
Both Isop and glucagon hyperpolarized the membrane and decreased the membrane resistance, to various degrees. Repetitive application of Isop or glucagon resulted in the disappearance of both Isop and glucagon‐induced hyperpolarizations. Pretreatment with NA not only resulted in a recovery of both Isop and glucagon‐induced hyperpolarizations, but also extensively enhanced the hyperpolarization.
After pretreatment with Isop, the NA‐induced hyperpolarization was decreased in amplitude and duration and was followed by a slowly developing depolarization. After repetitive application of Isop, NA produced only depolarization of the membrane, and in these conditions, Isop, glucagon or ATP also depolarized the membrane. These depolarizations were reversed to hyperpolarizations by pretreatment with excess [Ca]0.
After treatment with Na‐deficient solution, NA depolarized the membrane and decreased the membrane resistance. Excess [Ca]0 restored the NA‐induced membrane response from one of depolarization to one of hyperpolarization.
In the presence of tetraethylammonium 10mM, the NA‐induced hyperpolarization became transient or ceased and depolarization occurred with a reduction in the membrane resistance.
It is postulated that both NA and Isop increase the free [Ca]i by releasing bound Ca from storage sites and consequently an increase in K conductance follows. NA but not Isop promotes Ca‐influx which replenishes the storage site. In Ca‐depleted conditions, NA does not elevate the free [Ca]i to a threshold concentration required for hyperpolarization, probably because NA induces a small release of Ca from storage sites.
DISTRIBUTION OF P1 AND P2‐PURINOCEPTORS IN THE GUINEA‐PIG AND FROG HEART
Authors: BURNSTOCK GEOFFREY , MEGHJI PARVIZ 
Published: July 2012

The effects of adenyl compounds were examined on the guinea‐pig and frog heart in terms of the P1/P2‐purinoceptor hypothesis.
The effects of two slowly degradable adenosine 5′‐triphosphate (ATP) analogues; β, γ‐methylene adenosine 5′‐triphosphate (APPCP) and α, β‐methylene adenosine 5′‐triphosphate (APCPP) were also examined.
Adenosine, adenosine 5′‐monophosphate (AMP), adenosine 5′‐diphosphate (ADP), ATP and APPCP produced inhibitory effects in guinea‐pig atria. These inhibitory effects were antagonized competitively by theophylline and potentiated by dipyridamole. APCPP did not produce a similar inhibitory response.
Guinea‐pig ventricles were insensitive to adenyl compounds.
ATP and ADP produced initial excitatory effects in frog atria which were followed by inhibitory effects. Adenosine and AMP produced inhibitory effects alone whereas APCPP produced excitatory effects only. The inhibitory effects were antagonized competitively by theophylline and potentiated by dipyridamole.
ATP, ADP, APPCP and APCPP evoked excitatory responses in frog ventricles. These responses were not affected by theophylline or dipyridamole. Adenosine and AMP were inactive on frog ventricles.
It is concluded that only P1‐receptors are present in guinea‐pig atria; that both P1‐ and P2‐receptors are present in frog atria; and that only P2‐receptors are present in frog ventricles. No evidence was found for the presence of either P1 or P2‐purinoceptors in guinea‐pig ventricles.
EFFECT OF GENDER ON DEVELOPMENT AND DIURNAL RHYTHM OF PROSTAGLANDIN RECEPTORS IN RAT AORTA
Authors: KARANIAN J.W. , RAMEY E.R. , RAMWELL P.W. 
Published: July 2012

The prostaglandin endoperoxide H2 analogue, U‐46619 (15‐hydroxyll, 9‐epoxymethano‐prosta‐5Z, 13E‐enoic acid), was used to determine the effect of gender on the isotonic contractile response of the superfused rat aorta preparation over a 24 h period and at 10 and 16 weeks of age.
The maximal responses of the male aortae were 20 ± 3% and 36 ± 4% (P< 0.001) greater than the female at 10 and 16 weeks, respectively. Similarly, sensitivity of the male aorta to the PGH2 analogue increased with age.
The male but not the female exhibited a diurnal rhythm in which both the maximum contractile response and sensitivity were significantly decreased at night.
We conclude that these gender differences may be related to the secretion of androgen, since reported peak serum testosterone over a 24 h period and testosterone changes with maturation are coincident with the maximum response of male aortae to the PGH2 analogue.
EFFECT OF FATTY ACIDS ON THE VENTRICULAR ARRHYTHMIA THRESHOLD IN THE ISOLATED HEART OF THE RABBIT
Authors: MURNAGHAN MAURICE F. 
Published: July 2012

The ventricular arrhythmia threshold (VAT) was measured in the isolated Ringer‐perfused rabbit heart (Langendorff preparation) by applying a single 10 ms square‐wave pulse of current to the left ventricle during the vulnerable period of late systole under normoxic and hypoxic conditions.
The sodium salt of the fatty acid was bound to albumen and incorporated in the Krebs‐Henseleit solution which was maintained at 37°C and gassed with 95% O2 and 5% CO2 (normoxia) or 5% CO2 in air (hypoxia).
Saturated fatty acids failed to alter the VAT under normoxia.
Naturally occurring long‐chained saturated and mono‐unsaturated fatty acids with chain lengths varying from 14 to 20 carbons, but not the 12 carbon lauric acid, potentiated the effect of the hypoxia in lowering the VAT.
Short‐chained 8 and 10 carbon saturated and long‐chained polyunsaturated fatty acids antagonized the effect of hypoxia on the VAT.
In addition the polyunsaturated acids antagonized the potentiating effect of the long‐chained saturated and mono‐unsaturated acids on the hypoxia in lowering the VAT.
The fatty acids did not alter the duration or type of the induced arrhythmia.
THE PARTIAL PURIFICATION AND BIOASSAY OF A TOXIN PRESENT IN EXTRACTS OF THE SEA ANEMONE, Tealia felina (L.)
Authors: ALDEEN SUSAN I. , ELLIOTT R.C. , SHEARDOWN M. 
Published: July 2012

Column chromatography with Agarose A50m followed by Sephadex G100 was used to separate a fraction (extract II) in the molecular weight range 12,000 to 14,000 daltons from saline extracts of the sea anemone, Tealia felina.
Extract II inhibited histamine‐induced contractions of the guinea‐pig ileum and produced haemolysis of human blood, effects on which bioassays were based.
The potency of extracts was assayed. A standard unit of activity (= AU) was defined such that 100 AU produced 90% inhibition of histamine‐induced contractions of the guinea‐pig ileum after 30 to 35 min exposure.
The relationship between activity of the extracts measured on the ileum and their haemolytic activity was studied, providing a second assay method based on the latter property.
Based on values from both methods of assay, the calculated yield in AU at the end of the separation procedure was 0.53 AU for each AU present in the original extract. In crude extract there were 5.0 AU/mg dry weight and 36.7 AU/mg protein, and after separation (extract II) there were 11.2 AU/mg dry weight and 312.2 AU/mg protein.
The acute LD50 values determined in mice (i.v.) were: for crude extract 124 mg/kg, for extract I, 76 mg/kg and for extract II, 69 mg/kg.
Extract II (0.18 to 0.72 AU/ml) produced a slowly developing contraction of guinea‐pig ileum. Indomethacin (2.8 × 10−5 m) substantially reduced this response.
Extract II (0.03 AU/ml) reduced the contractile response of the guinea‐pig ileum to acetylcholine by 39 ± 8%, n = 6, and the response to histamine by 26 ± 6.6%, n = 6. The response to 5‐hydroxy‐tryptamine (5‐HT) was not reduced by 0.08 AU/ml of extract II, a concentration that actually increased the contractile response to KCl by 32 ± 11.2%, n = 7.
It is proposed that for future work on the extract a new AU should be used. This AU is defined such that 50 AU produce 50% inhibition of histamine‐induced contractions of the guinea‐pig ileum after 30 to 35 min exposure.
EFFECT OF SUBSTANCE P AND ITS NATURAL ANALOGUES ON GASTRIC EMPTYING OF THE CONSCIOUS RAT
Authors: BERTACCINI G. , DE CASTIGLIONE R. , SCARPIGNATO C. 
Published: July 2012

Substance P and its natural analogues were tested for their effect on gastric emptying in the rat.
Substance P and kassinin were virtually inactive even at the maximum dose tested.
The other tachykinins significantly delayed gastric emptying, their effect being quite remarkable with 100 μg/kg. The lowest doses (30 μg/kg) caused a slight and non‐significant increase in emptying rate.
The effect on gastric emptying was most probably correlated with a spasmogenic effect on the gastroduodenal junction, as pointed out in previous work.
5‐HYDROXYTRYPTAMINE INDUCES RELAXATION OF GOAT PULMONARY VEINS: EVIDENCE FOR THE NONINVOLVEMENT OF M AND D‐TRYPTAMINE RECEPTORS
Authors: CHAND NARESH 
Published: July 2012

Reactivity of goat isolated pulmonary arteries and veins to a variety of vasoactive agents was investigated.
Bradykinin (Bk), acetylcholine (ACh), noradrenaline (NA), prostaglandin A1 (PGA1), PGE2, PGF2α and histamine induced dose‐dependent contractile responses on veins; 5‐hydroxytryptamine (5‐HT) induced veno‐relaxation. Angiotensin was virtually inactive.
Angiotensin, NA, Bk, histamine and 5‐HT produced concentration‐dependent contractile responses on the arterial strips; these arteries failed to respond to ACh, PGA1, PGE2 or PGF2α.
The pulmonary veno‐relaxant response to 5‐HT was found to be resistant to propranolol, indomethacin, metiamide, cimetidine, methysergide, atropine and morphine. These findings appear to exclude the involvement of adrenergic mechanisms and prostaglandin generation as well as activation of classical M and D‐tryptamine receptors by 5‐HT in the goat pulmonary veins. This response may be mediated via a presynaptic inhibitory 5‐HT receptor.
5‐HT‐induced arterial contractile responses were antagonized by methysergide, showing the occurrence of classical D receptors in the goat pulmonary artery.
It is concluded that differential reactivity of pulmonary arteries and veins to vasoactive agents may play differential role(s) in the pathophysiology of pulmonary disease. 5‐HT may exert an antiinflammatory activity in goat pulmonary veins.
STEREOSPECIFIC DEXTRORPHAN TOLERANCE IN RATS
Authors: CARNEY JOHN M. , SIROCHMAN VICKI L. 
Published: July 2012

Levorphanol was 20 times more potent than dextrorphan in decreasing food‐reinforced fixed ratio 15 responding in male Sprague Dawley rats.
Chronic dextrorphan (100 mg/kg, i.p.; every 8 h) resulted in the development of dextrorphan tolerance. The dextrorphan dose‐effect curve was shifted to the right three fold.
In contrast to dextrorphan, nontolerance developed to the effects of levorphanol.
These data support the hypothesis that (+)‐isomers of opioids produce pharmacologically distinct CNS effects.
ANGIOTENSIN RECEPTORS IN BOVINE UMBILICAL ARTERY AND THEIR INHIBITION BY NONSTEROIDAL ANTI‐INFLAMMATORY DRUGS
Authors: GOODFRIEND THEODORE L. , SIMPSON ROBERT U. 
Published: July 2012

The contractile effect of angiotensin II on bovine isolated umbilical arteries was compared to [125I]‐angiotensin II binding by a subcellular fraction of that tissue. The ED50 of angiotensin was 3.1 ± 2.8 × 10−8 m, while the apparent dissociation constant was 4.9 ± 1.6 × 10−9 m.
Indomethacin, meclofenamate, and eicosatetraynoic acid inhibited angiotensin‐induced contraction of the isolated artery and binding to a particulate fraction at comparable doses. Phenylbutazone inhibited [125I]‐angiotensin binding more potently than the response. Inhibition by the first three agents was noncompetitive, whereas phenylbutazone inhibited competitively.
Inhibition of angiotensin activity by the nonsteroidal anti‐inflammatory agents was not specific. These agents also inhibited 5‐hydroxytryptamine‐induced contraction, but not the contraction induced by KCl.
The data suggest that the angiotensin binding sites studied include receptors that mediate contraction of the isolated umbilical artery. Our data also indicate that indomethacin, meclofenamate, eicosatetraynoic acid and phenylbutazone are capable of direct inhibitory effects on receptors, as well as their well‐known synthetase actions. The net effect of these activities will determine the change these agents cause in tissue responses to hormones.