bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of adenyl compounds on the rat heart
Authors: Burnstock Geoffrey , Meghji Parviz 
Published: July 2012

The effects of adenyl compounds were examined on the rat atrium and ventricle.
Adenosine, adenosine 5′‐monophosphate, adenosine 5′‐diphosphate, adenosine 5′‐triphosphate (ATP) and β, γ‐methylene ATP (APPCP) produced negative inotropic effects on the rat atrium. These inhibitory effects were antagonized by 8‐phenyltheophylline (8‐PT), a P1‐purinoceptor antagonist, and potentiated by erythro‐9‐(2‐hydroxy‐3‐nonyl) adenine (EHNA), an adenosine deaminase inhibitor, but were not affected by dipyridamole, which blocks adenosine uptake.
α, β‐Methylene ATP (APCPP), which is resistant to degradation, did not produce a similar inhibitory response in the rat atrium.
Adenosine did not affect the basal developed force of the rat ventricle nor did it affect the β‐adrenoceptor‐mediated positive inotropic effect.
Very high concentrations of ATP (0.1–3 mM) produced negative inotropic effects in the rat ventricle. APPCP (0.3 mM) also produced an inhibitory response, which was significantly smaller than that produced by ATP (0.3 mM). APCPP elicited excitation rather than the expected inhibitory response.
The inhibitory effect of ATP in the rat ventricle was not blocked by indomethacin, 8‐PT or atropine.
It impossible that the action of ATP in the rat ventricle is mediated via P2‐purinoceptors and that the lack of inhibitory action of APCPP on the rat ventricle is due to the difference in structural conformation between ATP and APCPP.
It seems likely that inhibitory P1‐purinoceptors are present in the rat atrium and that the inhibitory responses produced by ATP in the rat ventricle may be mediated via P2‐purinoceptors.
The effect of modification of sympathetic activity on responses to ligation of a coronary artery in the conscious rat
Authors: Botting J.H. , Johnston Kathleen M. , Macleod B.A. , Walker M.J.A. 
Published: July 2012

Ligation of a coronary artery was performed in conscious rats whose sympathetic system activity had been altered by various treatments.
β‐Adrenoceptor blockade with acute (0.2 mg kg−1 plus 0.1 μg kg−1 min−1) or chronic (50–60 mg kg−1 daily for 12 days) propranolol treatment had little effect on arrhythmias, or other responses to ligation.
Abrupt withdrawal of chronic propranolol two days before ligation was also without effect.
Reduction of sympathetic activity acutely with labetalol (5 mg kg−1), or chronically with adrenomedullectomy and 6‐hydroxydopamine treatment, accentuated the adverse effects of ligation.
The results of this study suggest that, while activity of the sympathetic system is not detrimental during ligation in the conscious rat, it may be important for survival.
Influence of dopamine receptor agonists on gastric acid secretion induced by intraventricular administration of thyrotropin‐releasing hormone in the perfused stomach of anaesthetized rats
Authors: Maeda‐Hagiwara Masaki , Watanabe Kazuo 
Published: July 2012

The influence of dopamine receptor agonists on gastric acid secretion stimulated by thyrotropin‐releasing hormone (TRH) was studied in the perfused stomach of anaesthetized rats.
Intraventricular TRH produced a dose‐dependent stimulation of basal gastric acid secretion.
Pretreatment with apomorphine, bromocriptine or methamphetamine inhibited the TRH‐stimulated gastric acid secretion; these drugs did not influence bethanechol‐induced acid secretion.
Haloperidol and metoclopramide prevented the antisecretory effects of apomorphine, bromocriptine and methamphetamine.
The present study suggests that central dopamine receptor stimulation inhibits intraventricular TRH‐induced gastric acid secretion in rats.
Dose‐dependent reduction in renal magnesium clearance by amiloride during frusemide‐induced diuresis in rats
Authors: Devane John , Ryan Michael P. 
Published: July 2012

The effects of the potassium‐sparing diuretic, amiloride, on fractional magnesium excretion were investigated at four doses (0.02, 0.08, 0.20 and 2.00 mg kg−1h−1) during frusemide‐induced diuresis.Amiloride caused a dose‐dependent reduction in the fractional excretion of both magnesium and potassium, whereas the effects of amiloride, over the same dose range, on fractional sodium and calcium excretion were not dose‐dependent.The results indicate that amiloride exerted a specific renal action to alter magnesium and potassium transport dissociated from effects on sodium excretion.
Gastric juice electrolyte secretion in conscious dogs with gastric fistulae and its modification by FPL 52694, a mast cell stabilizing agent
Authors: Canfield S.P. , Curwain B.P. 
Published: July 2012

Studies have been made of the electrolyte output in the gastric juice of conscious dogs equipped with gastric fistulae during stimulation by intravenous infusion of either pentagastrin (2 μg kg−1 h−1), histamine (30 μg kg−1 h−1) or insulin (0.1 u kg−1 h−1).
The mast cell stabilizing agent, FPL 52694 (4.35 mg ml−1) was instilled into the stomach for 30 min and caused a marked reduction of H+ output, H+ concentration and osmotic strength of the juice during stimulation with pentagastrin, histamine, or insulin. There was also a marked increase in the rate of Na+ output into the juice.
When pentagastrin‐stimulated acid secretion was inhibited by cimetidine (4 μmol kg−1 i.v.) acid output was reduced but there were no sustained changes in ion concentrations, osmolality or Na+ output of the type seen following inhibition with FPL 52694.
It is concluded that FPL 52694 may have a dual mode of action in this preparation; a direct reduction of the output of hydrochloric acid and a smaller effect to increase gastric NaHCO3 output leading to a post‐secretory neutralization of the juice.
Myocardial inotropic responses and adrenoceptors in protein‐deficient rats
Authors: Benfey B.G. , Varma D.R. , Yue T.L. 
Published: July 2012

Inotropic effects of isoprenaline, phenylephrine and calcium were studied in left atria of 5 weeks old rats fed a low (5%) or a normal (21%) protein diet for 3 weeks. Rats maintained on a low (5%) protein diet consume about half the amount of food eaten by the same rats maintained on a normal (21%) protein diet and thus suffer from protein‐calorie malnutrition (PCM).
Body weight did not increase in PCM, but heart weight adjusted to body weight was slightly increased compared to normal rats.
Atrial resting tension and peak developed tension in response to isoprenaline, phenylephrine or calcium were not diminished by PCM.
The number of a and β‐adrenoceptors and the receptor affinity in ventricular membranes were not reduced by PCM.
The spasmogenic action of potassium chloride in guinea‐pig trachealis
Authors: Foster R.W. , Small R.C. , Weston A.H. 
Published: July 2012

Tissue bath experiments showed that potassium chloride (KCl) at 10–40 mmol l−1 evoked spasm of guinea‐pig trachealis which was unaffected by atropine (1 μmol l−1), mepyramine (1 μmol l−1), tetrodotoxin (3 μmol l−1) or indomethacin (2.8 μmol l−1).
Spasm evoked by KCl was depressed in Ca2+‐free Krebs solution or by exposure of tissues to LaCl3 (0.25–1 mmol l1).
Extracellular electrical; recording showed that the spasm evoked by KCl 10 mmol l−1 was associated with promotion of electrical slow wave activity. Higher concentrations of KCl abolished slow wave activity but caused further tension development.
Intracellular recording confirmed the ability of KCl 10 mmol l−1 transiently to promote slow wave activity in individual trachealis cells. This action was associated with depolarization and tension development. Higher concentrations of KCl evoked further tension development but slow waves were suppressed as the depolarization evoked by KCl increased.
KCl (10–40 mmol 1−1) increased the lanthanum‐resistant calcium fraction of muscle‐containing strips of trachea.
It is concluded that KCl acts directly on the smooth muscle of guinea‐pig trachea. The spasmogenic action is associated with transient promotion of slow wave activity and a fall in resting membrane potential. The spasm involves the cellular influx of Ca2+ and is dependent on the presence of Ca2+ in the extracellular fluid.
Motoneurone excitability after administration of a thyrotrophin releasing hormone analogue
Authors: Clarke K.A. , Stirk G. 
Published: July 2012

Recordings have been made of motoneurone field potentials at vertebral level L1 to stimulation of the ventral root, in rats anaesthetized with urethane.
Injection of thyrotrophin releasing hormone (TRH) analogue RX77368 (2 mg kg−1) produced an increase in the amplitude of the field potential within 1 min of injection, reaching peak amplitude of 51–69% above control values 6–12 min after injection; the duration of the elevation was 30–65 min.
Arguments are presented which show that this effect is compatible with an RX77368‐induced depolarization of the motoneurone, allowing the antidromic volley to invade more cell bodies.
Interactions between alinidine and responses to acetylcholine, dopamine and 5‐hydroxytryptamine of specific Helix central neurones
Authors: Bokisch Anita J. , Walker R.J. 
Published: July 2012

Intracellular recordings were made from identified neurones in the brain of the snail, Helix aspersa. The effect of alinidine on the excitatory and inhibitory responses to acetylcholine and dopamine and on the excitatory response to 5‐hydroxytryptamine (5‐HT) was investigated.
Alinidine was found to reduce the responses to acetylcholine and 5‐HT and the excitatory response to dopamine but had no effect on the dopamine inhibitory response. pA2 values were determined for alinidine antagonism to indicate relative potency. The pA2 values against the excitatory responses of acetylcholine, dopamine and 5‐HT were 5.8, 5.6 and 5.5 respectively. The pA2 value against acetylcholine inhibition was 3.5.
From these studies it is suggested that alinidine interacts preferentially with the sodium ionophore, to a lesser degree with the chloride ionophore and not at all with the potassium ionophore on Helix central neurones.
Effect of 781094, a new selective α‐adrenoceptor antagonist, on the aggregatory responses of human blood platelets and on binding of [3H]‐dihydroergocryptine to these cells
Authors: Kerry Roger , Scrutton Michael C. 
Published: July 2012

781094 (2‐(2(1, 4‐benzodioxanyl))‐2‐imidazoline hydrochloride) is a potent competitive inhibitor of the aggregatory responses of human platelets induced by adrenaline (pA2 = 7.3) and UK‐14304.
781094 is a more potent inhibitor of the pro‐aggregatory response to clonidine than of that to methoxamine. The α2/α1‐adrenoceptor selectivity ratio is 11.4.
781094 is a potent inhibitor of the binding of [3H]‐dihydroergocryptine to platelet lysates.
781094 has no effect on the aggregatory responses of human platelets induced by adenosine‐5′‐pyrophosphate (ADP), 5‐hydroxytryptamine, thrombin, U‐46619, or arginine‐vasopressin provided that the platelet‐rich plasma does not exhibit enhanced responsiveness. In some instances high concentrations of 781094 potentiate the aggregatory response to collagen.
In platelet‐rich plasma which exhibits enhanced responsiveness, 781094 causes partial inhibition of the aggregatory responses to 5‐hydroxytryptamine, ADP and vasopressin at concentrations similar to those required to inhibit the response to adrenaline.
781094 acts as a specific antagonist for the responses mediated by human platelet α‐adrenoceptors and exhibits moderate selectivity for the α2‐adrenoceptors on this cell.
Cyclic adenosine 3′,5′‐monophosphate and β‐effects in rat isolated superior cervical ganglia
Authors: Brown D.A. , Dunn P.M. 
Published: July 2012

Isoprenaline (0.01–1 μm) increased the amount of cyclic adrenosine 3′,5′‐monophosphate (cyclic AMP) in rat isolated superior cervical ganglia by up to 10 times after 10 min application. Cyclic AMP levels returned to control values after 20 min washing.
Salbutamol, in concentrations (1–100 μm) that depolarized the ganglion and facilitated submaximal transmission, did not significantly raise ganglionic cyclic AMP levels.
The action of isoprenaline was antagonized by butoxamine (apparent KI≅0.14 μm) and weakly by practolol (apparent KI≅9.1 μm).
The effect of 0.1 μm isoprenaline was also inhibited 94% by 100 μm of the adenylate cyclase inhibitor, 9‐(tetrahydro‐2‐furyl)adenine (SQ 22,536).
Exogenous dibutyryl cyclic AMP did not replicate the effects of isoprenaline on ganglionic d.c. potentials or submaximal transmission.
The phosphodiesterase inhibitors theophylline, isobutylmethylxanthine or 4‐(3,4‐dibutoxybenzyl)‐2‐imidazolidinone (Ro 20–1724) did not potentiate these electrical responses to isoprenaline.
The adenylate cyclase inhibitor, SQ 22,536, did not inhibit the electrical responses to isoprenaline.
It is concluded that available evidence does not support the view that the ganglion depolarization or facilitation of submaximal transmission in rat isolated ganglia produced by isoprenaline are likely to be mediated by cyclic AMP.
The effects of altered thyroid state upon responses mediated by atrial muscarinic receptors in the rat
Authors: Ishac E.J.N. , Pennefather Jocelyn N. 
Published: July 2012

Untreated rats, and rats treated with methimazole (0.05% w/v in drinking water) or thyroxine (1 mg/kg, s.c., three times weekly) for 4–6 weeks to induce hypo‐ and hyperthyroidism respectively, were used to study the influence of thyroid hormone upon negative chronotropic and inotropic responses mediated by cardiac muscarinic receptors, and upon the affinity of these receptors for atropine.
Negative chronotropic effects of methacholine were investigated by establishing partial concentration‐response curves for isolated preparations of right atria. Methacholine was least potent in tissues from thyroxine‐treated rats.
Isolated left atria paced at 3 Hz, and spontaneously beating right atria, were used in studies of the negative inotropic effects of methacholine. This agonist was least potent in atria from the thyroxine‐treated rats in which it also produced the smallest maximal responses.
The negative inotropic effects of carbachol were examined on left atria paced at 3, 5 and 5.8 Hz to approximate the basal contraction rates of isolated right atria from methimazole‐treated, untreated control and thyroxine‐treated rats, respectively. At each of these frequencies, carbachol was most potent in atria from methimazole‐treated rats, and least potent in atria from thyroxine‐treated rats. Maximal responses were smallest in the latter group.
pA2 values for atropine with methacholine as the agonist were obtained by the method of Arunlakshana & Schild (1959) for spontaneously beating right atria (negative chronotropic and inotropic effects) and left atria paced at 3 Hz (negative inotropic effects). Slopes of Schild plots did not differ from minus one in tissues from each of the experimental groups; pA2 values were similar, indicating that thyroid status is without effect upon the affinity of this antagonist for muscarinic receptors mediating both negative inotropic and chronotropic effects.
The results are discussed in the light of reports that hypothyroidism increases, and hyperthyroidism decreases the numbers of high affinity muscarinic receptor binding sites in the rat myocardium.
Temperature‐induced changes in dissociation constants (KA) of agonists at cardiac β‐adrenoceptors determined by use of the irreversible antagonist Ro 03–7894
Authors: Broadley Kenneth J. , Williams Russell G. 
Published: July 2012

The positive inotropic responses of guinea‐pig left atria and papillary muscles and positive chronotropic responses of right atria to sympathomimetic amines were examined at 38° and 30°C.
At the lower temperature, supersensitivity to orciprenaline and isoprenaline was exhibited as shifts of the dose‐response curves to the left and significant reductions in EC50 values.
This supersensitivity could not be attributed to reduced metabolism since the experiments were performed in the presence of metanephrine (10−5m) and U‐0521 (3×, 4×‐dihydroxy‐2‐methylpropiophenone) (10−4m) as inhibitors of extraneuronal uptake and catechol‐O‐methyltransferase (COMT) respectively, and the agonists are not susceptible to neuronal uptake.
After incubation of the tissues with Ro 03–7894 (1‐(5‐chloracetylaminobenzfuran‐2‐yl)‐2‐isopropylaminoethanol), followed by its prolonged washout (> 2h), the maximum responses to isoprenaline and orciprenaline were depressed, confirming the apparently irreversible β‐adrenoceptor antagonism.
Dissociation constants (KA) for isoprenaline and orciprenaline were determined from the equiactive concentrations obtained before (A) and after (A′) incubation with Ro 03–7894, plotted as 1/A against 1/A′ (KA = (slope — 1)/intercept).
KA values were the same for orciprenaline in the three cardiac preparations and for isoprenaline in the atria. This applied at 38° and 30°C and indicates that the β‐adrenoceptors mediating the inotropic and chronotropic responses of the guinea‐pig heart do not differ.
The KA values of both agonists were, however, consistently and significantly lower at 30° than at 38°C, indicating an increase in affinity.
It is concluded that hypothermia‐induced supersensitivity of cardiac tissue to sympathomimetic amines is associated with an increase in their affinity for the β‐adrenoceptors.
Modulation of the concentration of noradrenaline at the neuro‐effector junction in human saphenous vein
Authors: Janssens Walter , Verhaeghe Raymond 
Published: July 2012

We studied the importance of neuronal and extraneuronal uptake and of the pre‐junctional α‐adrenergic feed‐back mechanism for the junctional noradrenaline concentration in the human saphenous vein. All major metabolites of the enzymatic breakdown of noradrenaline were detected in the overflow of superfused veins loaded with [3H]‐noradrenaline. The efflux of 3,4‐dihydroxyphenylglycol (DOPEG) was drastically reduced in preparations labelled after neuronal uptake blockade indicating its neuronal origin; the other metabolites are formed extraneuronally since they behaved distinctly differently from DOPEG under several experimental conditions.
Extraneuronal uptake followed by enzymatic breakdown removes the same amount of noradrenaline from the biophase during nerve activity as that diffusing intact out of the tissue, whereas neuronal uptake appears only half as effective since the overflow of intact noradrenaline increases by only 48% in the presence of desmethylimipramine (DMI). However, in preparations mounted for isometric tension recording, neuronal uptake blockade potentiated contractions to α‐adrenergic activation, emphasizing the functional importance of the neuronal disposition mechanism. By contrast, no evidence was found for a hydrocortisone‐sensitive extraneuronal uptake compartment, suggesting that extraneuronal removal may have little, if any, functional importance.
During nerve stimulation, yohimbine increased the amount of labelled noradrenaline present in the superiusate, while exogenously added noradrenaline decreased it in the presence of cocaine. Thus, prejunctional α‐adrenoceptors can modulate the junctional concentration of neurotransmitter in the human saphenous vein.
Specificity and inhibition of glucocorticoid‐induced macrocortin secretion from rat peritoneal macrophages
Authors: Blackwell Geoffrey J. 
Published: July 2012

The secretion of the phospholipase A2‐inhibitor macrocortin and the binding of dexamethasone were studied in suspensions of rat peritoneal macrophages.
Corticosteroid‐induced macrocortin secretion was specific for glucocorticoids and did not occur in response to glucocorticoid antagonists or other steroids or in response to non‐steroid macrophage activators (formyl‐methionyl‐leucyl‐phenylalanine f‐MLP), the calcium ionophore A23187, phorbol myristate acetate (PMA) and lipopolysaccharide‐E.‐coli(LPS)).
The apparent potency of competition by secretory glucocorticoids for dexamethasone binding to the macrophage parallelled their ability to induce secretion, implying that these binding sites represent the receptors by which macrocortin secretion is initiated.
Agents which interfere with microtubule assembly (colchicine, vinblastine and trimethylcol‐chicinic acid) and prostacyclin and dibutyryl cyclic AMP inhibit macrocortin secretion.
Inhibition studies of glucocorticoid‐induced macrocortin secretion also suggest dependence upon metabolic energy, a source of Ca2+ and proteolysis and glycosylation prior to secretion.
Effect of metoprolol on 24‐hour urinary excretion of adrenal steroids and kallikrein in patients with essential hypertension
Authors: Fritschka E. , Gotzen R. , Kittler R. , Schöneshöfer M. 
Published: July 2012

Treatment of fifteen patients with essential hypertension over four weeks using the β‐adrenoceptor blocking agent, metoprolol, resulted in a decrease in 24 h urinary excretion of kallikrein and aldosterone along with a decrease in plasma renin activity.There was no significant change in 24 h excretion rates of the free adrenal steroids deoxycorticosterone, 18‐OH‐deoxycorticosterone, corticosterone, cortisol or 18‐OH‐corticosterone during treatment, which were not significantly different from excretion rates of normal males, thus excluding inhibitory effects of adrenal steroids on urinary kallikrein activity.A positive correlation was found between plasma renin activity and urinary excretion of kallikrein during the control period and after 2 weeks on metoprolol, supporting the assumption of a preserved link between the renin‐angiotensin‐aldosterone system and the renal excretion of kallikrein in these patients.The decrease in kallikrein excretion during β1‐adrenoceptor blockade in patients with essential hypertension may be explained by a reduction in sympathetic tone and by reduced activity of the renin‐aldosterone system.
Inhibitory effects of centrally acting drugs on the neonatal imprinting of sex differences in the hepatic metabolism of a dimethylated epoxide in the rat
Authors: Finnen Michael J. , Hassall Kenneth A. 
Published: July 2012

The effects of the neonatal administration of reserpine, chlorpromazine, phenobarbitone and morphine on the development of sex differences in hepatic drug metabolism in the rat have been investigated.
Treatment of neonatal male rats with reserpine or chlorpromazine for the first two weeks post‐partum significantly inhibited the development of sex differences in drug metabolism in adult life.
Similar treatment of neonatal female rats with reserpine or chlorpromazine had no effect on the development of hepatic drug metabolism in adulthood.
Morphine or phenobarbitone treatment of neonatal rats of either sex had no effect on the development of sex differences in hepatic drug metabolism in adult life.
Are there α‐adrenoceptors in the young chick atria?
Authors: Tayo Fola M. 
Published: July 2012

The effect of noradrenaline and isoprenaline were studied in the 15‐day old chick atria. Noradrenaline increased both the rate and force of atrial contractions whilst isoprenaline only slightly increased force at very high concentrations.
The increase in force after noradrenaline and isoprenaline was reduced by phentolamine, an α‐adrenoceptor antagonist. The β‐antagonist, propranolol and the cardioselective β1‐adrenoceptor antagonist, atenolol, did not reduce the positive inotropy. Noradrenaline‐induced positive chronotropy was, however, resistant to both α‐ and β‐adrenoceptor blockade.
It is concluded that the force of contraction of the chick atria may be α‐adrenoceptor‐mediated whilst the rate seems to be mediated by a mechanism sensitive to noradrenaline but insensitive to α‐and β‐adrenoceptor blockade.