bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CHEMOTACTIC ROLE FOR PROSTAGLANDINS RELEASED FROM POLYMORPHONUCLEAR LEUCOCYTES DURING PHAGOCYTOSIS
Authors: HIGGS G.A. , McCALL ELAINE , YOULTEN L.J.F. 
Published: July 2012

Prostaglandin E1 is chemotactic at concentrations down to 10 ng/ml for rabbit polymorphonuclear (PMN) leucocytes. Prostaglandins E2 and F2α have little or no chemotactic effect at concentrations up to 10 μg/ml.
Washed PMN leucocytes produce a chemotactic agent during phagocytosis, but not in the presence of indomethacin (28 μM).
Phagocytosing PMN leucocytes produce up to ten times as much prostaglandin as do resting cells. Some of this is prostaglandin E1 as judged by thin layer chromatography and differential bioassay. This prostaglandin production by PMN leucocytes is abolished by indomethacin (28 μM).
Ultrasonicated suspensions of PMN leucocytes produce prostaglandin from arachidonic acid. This synthesis is inhibited by indomethacin.
Homogenates of PMN leucocytes which have been pre‐incubated with bacteria for 30 min show more prostaglandin synthetase activity than homogenates from PMN leucocytes which have not been exposed to bacteria.
It is concluded that in some forms of inflammation, prostaglandin E1 may play a controlling role in cellular migration.
PMN leucocytes may contribute to the generation of prostaglandins found in some inflammatory lesions.
COMBINED α‐ AND β‐ADRENOCEPTOR BLOCKING DRUG AH 5158: FURTHER STUDIES ON α‐ADRENOCEPTOR BLOCKADE IN ANAESTHETIZED ANIMALS
Authors: KENNEDY I. , LEVY G.P. 
Published: July 2012

AH 5158, 5‐[1‐hydroxy‐2‐[(1‐methyl‐3‐phenylpropyl)amino]ethyl]salicylamide, competitively antagonised phenylephrine‐induced vasopressor responses in anaesthetized dogs, thus confirming that the drug possesses α‐adrenoceptor blocking activity.
In contrast, AH 5158 was a relatively ineffective antagonist of vasopressor responses to noradrenaline in anaesthetized dogs. Thus, at the lowest dose‐level tested (1 mg/kg) AH 5158 abolished the increase in pulse width caused by noradrenaline, but otherwise had little or no blocking effect in doses as high as 10 mg/kg. Propranolol (0.1 mg/kg) also abolished the increase in pulse width caused by noradrenaline. With both drugs this effect is thought to be a consequence of blockade of the β‐adrenoceptor‐mediated cardiac stimulant action of noradrenaline.
The interaction between AH 5158 and noradrenaline in spinal dogs, anaesthetized cats and pithed rats was very similar to that seen in anaesthetized dogs.
Noradrenaline pressor responses were effectively antagonized by AH 5158 in anaesthetized dogs pretreated with cocaine. The degree of block was similar to that obtained when phenylephrine was the agonist in untreated dogs.
These results are consistent with the hypothesis that AH 5158 blocks a cocaine‐sensitive inactivation process for noradrenaline in addition to blocking α‐ and β‐adrenoceptors. The resultant increase in the level of circulating noradrenaline would tend to counteract the adrenoceptor blocking action of the drug.
The implications of these findings are discussed.
CENTRAL EFFECTS OF CLONIDINE 2‐(2,6‐DICHLOROPHENYLAMINO)‐2‐IMIDAZOLINE HYDROCHLORIDE IN FOWLS
Authors: MARLEY E. , NISTICÒ G. 
Published: July 2012

The effects of clonidine infused into the IIIrd cerebral ventricle, the hypothalamus or intravenously were studied on behaviour, electrocortical activity, body, comb and leg temperatures, respiration and carbon dioxide elimination in adult and young fowls (Gallus domesticus).
Behavioural and electrocortical slow wave sleep were induced by clonidine infused into Illrd cerebral ventricle, the hypothalamus or intravenously. Surprisingly, sleep elicited by intravenous clonidine was much longer‐lasting than that induced by an identical dose given intraventricularly.
Body temperature was lowered by clonidine given intraventricularly or infused into the hypothalamus. Depending on initial comb temperature and ambient temperature, comb temperature was elevated, unaffected or lowered as body temperature fell; temperature of the unfeathered legs also rose as body temperature declined after clonidine.
Following clonidine, but before any considerable decline of body temperature, tachypnoea and wing abduction developed; during recovery of body temperature, the wings were lowered and applied closely to the trunk and the feathers partly erected.
CO2 elimination fell more swiftly than body temperature following intrahypothalamic clonidine in young chicks; initial recovery developed sooner than that of body temperature, but eventual recovery was delayed compared to that for body temperature. The effects of clonidine were much more marked in young chicks studied at an ambient temperature below thermoneutrality as compared to thermoneutrality.
The soporific effects of clonidine were attenuated by intraventricular phentolamine; its hypothermic effects were prevented by phenoxybenzamine and prevented or attenuated by phentolamine. Intraventricular atropine, haloperidol, methysergide and propranolol were ineffective.
Larger doses of intraventricular phentolamine elicited shivering, tachypnoea and wing abduction; body temperature was elevated, to the extent even of lethal hyperthermia. Intraventricular atropine also elevated body temperature.
Clonidine infused intravenously, intraventricularly or into the hypothalamus, replaced the behavioural and electrocortical arousal evoked with dexamphetamine, by sleep associated with slow wave electrocortical activity.
EFFECTS OF DOPAMINE ON SINUS RATE AND VENTRICULAR CONTRACTILE FORCE OF THE DOG HEART in vitro AND in vivo
Authors: ENDOH M. 
Published: July 2012

Experiments were carried out on dog isolated papillary muscle and sinus node preparations perfused with arterial blood from a donor dog. The chronotropic and inotropic effects of dopamine were analysed by using reserpine, desmethylimipramine (DMI), cocaine and phenoxybenzamine, and the relative chronotropic and inotropic effects defined, the results being compared with those for noradrenaline (NA).
The effects of dopamine administered intra‐arterially into the isolated preparations were reduced by pretreatment of animals with reserpine both in the papillary muscle and sinus node. The chronotropic effects, however, were affected less by pretreatment with reserpine than were the inotropic effects.
Desmethylimipramine (DMI) reduced the inotropic and chronotropic effects of dopamine, and enhanced the effects of NA and nerve stimulation; the chronotropic effects of the amines were less affected than the inotropic effects.
Cocaine enhanced considerably the inotropic and chronotropic effects of NA, and decreased the inotropic but not the chronotropic effect of dopamine.
Phenoxybenzamine enhanced the inotropic effects of dopamine, NA and nerve stimulation, but did not affect the chronotropic effects of the amines.
When dopamine (1 to 300 μg/kg) was administered intravenously to the donor dog, it increased preferentially the contractile force of the ventricular myocardium with a comparatively small change of the sinus rate in the isolated preparations as well as in the heart in vivo. NA (0.1 to 10 μg/kg) caused effects similar to those of dopamine. The maximal inotropic responses to these catecholamines were reached with lower doses than the chronotropic ones.
It is concluded that both the positive inotropic and the positive chronotropic responses to dopamine are mediated partially by a direct and partially by an indirect stimulant effect on β‐adrenoceptors in the dog heart. The present results suggest that the difference in activity of dopamine and NA between the ventricular myocardium and the sinus node may be ascribed to the unequal innervation with adrenergic nerve fibres of the atrium and the ventricle (Furnival, Linden & Snow, 1971). The sinus node which is densely innervated by adrenergic nerve fibres may inactivate noradrenaline and dopamine more effectively than the ventricular myocardium through the uptake into the nerve and thereby be less sensitive to the exogenous catecholamines.
VENTRAL ROOT RESPONSES OF THE HEMISECTED AMPHIBIAN SPINAL CORD TO PERFUSED AMINO ACIDS IN THE PRESENCE OF PROCAINE
Authors: EVANS R.H. , WATKINS J.C. 
Published: July 2012

The use of the procaine‐blocked hemisected spinal cord preparation to identify the primary action of amino acids and their antagonists on amphibian motoneurones is described.
Apart from an anomalous effect of glycine, the responses of frog spinal motoneurones to amino acids were shown to be similar to those of mammalian spinal neurones.
In the presence of procaine, γ‐aminobutyrate (GABA), taurine and β‐alanine caused a hyperpolarizing response, measured in ventral roots, whereas L‐glutamate and, to a lesser extent, glycine caused depolarization.
Picrotoxin and bicuculline specifically blocked ventral root responses to GABA; strychnine blocked responses to taurine and β‐alanine but not responses to L‐glutamate, glycine or GABA.
THE EFFECTS OF LITHIUM IONS ON THE ANTIDIURETIC ACTION OF VASOPRESSIN IN THE RAT
Authors: JENNER F.A. , MACNEIL SHEILA 
Published: July 2012

The effect of intravenous infusion of lithium, 2.56 μmol/min on the antidiuretic responses to antidiuretic hormone (ADH), adenosine triphosphate (ATP), 3′‐5′ adenosine cyclic monophosphate (cyclic AMP) and theophylline was studied in water‐loaded, alcohol‐anaesthetized rats.
Lithium reversibly inhibits the antidiuretic response to all concentrations of ADH, depressing the maximum response but not changing the amount required for half maximal response.
The rate of increase of serum lithium relates more clearly to the inhibitory effect than does the serum concentration.
Sodium concentrations in the renal papilla seem to fall when serum lithium levels are rising.
Lithium inhibits the antidiuretic response to ATP and cyclic AMP but does not inhibit the response to theophylline.
THE INFLUENCE OF METYRAPONE ON THE SYNTHESIS AND RELEASE OF PROSTAGLANDINS FROM THE PREGNANT RAT UTERUS in vitro
Authors: PARNHAM M.J. , SNEDDON J.M. 
Published: July 2012

Metyrapone (150 mg/kg, s.c. or i.p.) an inhibitor of corticosteroid biosynthesis, significantly reduced the release of prostaglandins of the F‐type from isolated preparations of pregnant rat uteri in vitro, on day 22 ‐ the expected day of delivery.
Metyrapone and indomethacin administered in vitro both inhibited the conversion of 14C‐arachidonic acid to prostaglandin E2 by homogenates of day 22 pregnant rat uteri. Metyrapone was approximately 150 times less potent than indomethacin. Although indomethacin also inhibited prostaglandin F2α production, metyrapone stimulated synthesis of this prostaglandin. The differential inhibition of prostaglandin synthesis by metyrapone may reflect sensitivity of the inhibitor to changes in experimental conditions.
Inhibition of prostaglandin synthesis may explain the effects of metyrapone on parturition in the rat.
TOLERANCE TO SYMPATHOMIMETIC BRONCHODILATORS IN GUINEA‐PIG ISOLATED LUNGS FOLLOWING CHRONIC ADMINISTRATION in vivo
Authors: BENOY CHRISTINE J. , EL‐FELLAH M.S. , SCHNEIDER R. , WADE O.L. 
Published: July 2012

Pretreatment of the guinea‐pig subcutaneously three times daily with either 5 μg/kg isoprenaline or adrenaline reduced the response of the isolated perfused histamine‐constricted lung when challenged with either the same or a different sympathomimetic bronchodilator. The longer the animals were pretreated and the higher the dose of bronchodilator the greater was the degree of tolerance developed.
Tolerance was developed to aminophylline in the same preparation when the guinea‐pig had been pretreated with aminophylline or isoprenaline. Cross‐tolerance also developed to adrenaline when the guinea‐pig had been pretreated with aminophylline.
Tolerance was still persistent in guinea‐pigs one and two weeks after pretreatment three times daily with either isoprenaline or adrenaline (5 μg/kg s.c.) for seven days in the same preparation. Only after three weeks was the tolerance diminished.
These results suggest that asthmatic patients who use bronchodilators excessively may become refractory to the bronchodilator effect of these drugs. They also support the hypothesis that induced cross‐resistance to endogenous sympathetic stimulation could lead to a deterioration of the asthmatic state in patients using the sympathomimetic bronchodilators and that this may explain the increase in asthma mortality rate.
A mechanism of tolerance to sympathomimetic bronchodilators is postulated.
INNERVATION BOTH OF PERI‐ORBITAL STRUCTURES AND OF THE HEART BY THE CERVICAL SYMPATHETIC NERVES IN MOUSE, RAT, GUINEA‐PIG, RABBIT AND CAT
Authors: LARGE B.J. 
Published: July 2012

In anaesthetized rats electrical stimulation of the intact cervical sympathetic nerve produced frequency‐dependent lower eyelid contractions and tachycardia.
The tachycardia was caused by excitation of efferent fibres since it was equally evident in the pithed rat preparation, and the right nerve was more effective than the left. By contrast, no differences were seen between the responses to right and left vagal stimulation in either rats or rabbits.
Guanethidine inhibited both cardiac and eyelid responses, propranolol only the former and phentolamine only the latter, thereby revealing the adrenergic nature of the nerves. Hexamethonium caused partial inhibition and the block was intensified by atropine.
The inferior eyelid of mice, guinea‐pigs and rabbits as well as the nictitating membrane of rabbits and cats were contracted by cervical sympathetic nerve stimulation. In these species too, tachycardia occurred; this was more pronounced with the right than the left sympathetic nerve. The order of cardiac responsiveness was mouse > rat > guinea‐pig > rabbit > cat.
In guinea‐pigs histamine‐induced bronchoconstriction was reduced by cervical sympathetic nerve stimulation.
That discrete cardiac pathways exist in the cervical sympathetic nerves is suggested by the reproducibility of the effects within any one species. The accessibility of the nerves greatly simplifies the examination of drugs in vivo on two different structures innervated by the sympathetic nervous system.
TEMPERATURE AND BEHAVIOURAL RESPONSES INDUCED IN THE UNANAESTHETIZED CAT BY THE CENTRAL ADMINISTRATION OF RX72601, A NEW ANTICHOLINESTERASE
Authors: METCALF G. , MYERS R.D. , REDGRAVE P.C. 
Published: July 2012

The central effects produced by a new anticholinesterase RX72601 injected into the cerebral ventricles or perfused within circumscribed forebrain structures have been investigated in the unanaesthetized cat.
When injected into the cerebral ventricles in doses of 1–10 μg, RX72601 produced a dose‐related hyperthermia together with behavioural and autonomic responses.
Experiments designed to localize the site or sites of these actions demonstrated that hyperthermia could be produced from several diencephalic sites but that the other effects were not normally produced from these same sites.
EFFECTS OF IPRINDOLE ON RESPONSES OF SINGLE CORTICAL AND CAUDATE NEURONES TO MONOAMINES AND ACETYLCHOLINE
Authors: BEVAN P. , BRADSHAW C.M. , SZABADI E. 
Published: July 2012

The technique of microelectrophoresis was used to study the effects of iprindole on single neurones in the cerebral cortex and caudate nucleus of the rat.
Iprindole, when applied for a brief period, did not affect the firing rate of the vast majority of neurones tested.
Both potentiation and antagonism of neuronal responses to noradrenaline, dopamine, and 5‐hydroxytryptamine could be observed after a brief application of iprindole. Potentiation and antagonism often occurred after the same application of iprindole, antagonism always preceding potentiation.
Responses to acetylcholine were affected by iprindole similarly: both potentiation and antagonism of the responses could be observed.
Responses to glutamate were not affected by iprindole.
It is concluded that the potentiation of responses to monoamines by iprindole cannot be explained on the basis of uptake blockade; this potentiation may be due to the blockade of masked receptors on the post‐synaptic cell.
It is suggested that the common pharmacological action of the tricyclic antidepressants may be the ability to block both monoamine and acetylcholine receptors in the brain.
MECHANICAL RESPONSES OF RAT ISOLATED UTERINE HORNS TO TRANSMURAL STIMULATION
Authors: HOLLINGSWORTH M. 
Published: July 2012

Transmural stimulation of rat isolated uterine horns at low pulse width produced contractions. These were antagonized by hyoscine or tetrodotoxin and potentiated by physostigmine.
In the presence of hyoscine, and during bradykinin‐induced contractions, transmural stimulation produced inhibition. This inhibition was antagonized by guanethidine, propranolol or tetrodotoxin.
Hexamethonium or pempidine did not affect responses to transmural stimulation.
It is suggested that transmural stimulation is a method of exciting cholinergic motor and noradrenergic inhibitory postganglionic neurones to the rat myometrium.
MEDIATORS OF PASSIVE LUNG ANAPHYLAXIS IN THE RAT
Authors: FARMER J.B. , RICHARDS I.M. , SHEARD P. , WOODS AUDREY M. 
Published: July 2012

Passive lung anaphylaxis (PLA) was investigated in rats sensitized by the intravenous injection of high titre reaginic antiserum prepared in rats.
The effect of various pharmacological antagonists on anaphylactic bronchoconstriction in vivo were examined. An antihistamine (mepyramine), a kallikrein inactivator (aprotinin) or a prostaglandin synthesis inhibitor (aspirin) did not inhibit PLA, whereas an anti‐5‐hydroxytryptamine agent (methysergide) and an anti‐slow reacting substance‐A agent (FPL, 55712) significantly reduced the response.
Isolated perfused lungs taken from sensitized rats released, on challenge with the sensitizing antigen, histamine, 5‐hydroxytryptamine, slow reacting substance of anaphylaxis (SRS‐A) and prostaglandins, but no rabbit aorta contracting substance (RCS).
Disodium cromoglycate inhibited both anaphylactic bronchoconstriction in vivo and the anaphylactic release of mediators in vitro. Inhibition in vivo was dose‐related.
Mediators from the intestine, the primary shock organ of anaphylaxis in the rat, did not contribute to the lung response.
Vagal reflex pathways were found not to be important in PLA in vivo.
The relationship between the mediators released following antigen challenge of passively sensitized rat lung in vitro and passive lung anaphylaxis in vivo is discussed.
ANTI‐INFLAMMATORY ACTION OF GLUCAGON IN RATS
Authors: LEME J. GARCIA , MORATO M. , SOUZA MARIA ZENILDE A. 
Published: July 2012

Subcutaneous administration of glucagon (1 and 0.5 mg/kg) 30 min before the injection of carrageenin or dextran into the rat's paw reduced oedema and the local exudation of Evans blue previously given intravenously.
The effect persisted after removal of the adrenal medulla but not after adrenalectomy.
When glucagon (1 mg/kg, s.c.) was given daily after a local reaction to Freund's adjuvant injected into the paw had developed, a decrease in the reaction was observed up to 12 days. Blood sugar levels remained within the normal range.
Glucagon may exert an anti‐inflammatory effect through the release of adrenal corticosteroids and thus help modulate inflammatory reactions.
FORMATION OF DOPAMINE AND NORADRENALINE IN RAT VAS DEFERENS: COMPARISON WITH GUINEA‐PIG VAS DEFERENS
Authors: BOADLE‐BIBER MARGARET C. , ROTH R.H. 
Published: July 2012

The formation of [14C]‐3,4‐dihydroxyphenylalanine (DOPA) from [14C]‐tyrosine, in the presence of the amino acid decarboxylase inhibitor, brocresine (3‐hydroxy‐4‐bromobenzyloxy‐amine dihydrogen phosphate), was greatly enhanced in rat vasa deferentia depolarized by a KCl‐enriched Krebs‐Henseleit solution (52 mM KCl) compared with tissues maintained in unmodified Krebs‐Henseleit solution.
When the conversion of tyrosine was allowed to proceed as far as catecholamine (brocresine absent) no significant difference was observed between the accumulation of [14C]‐catecholamines (CA) in depolarized rat vasa deferentia and the accumulation in control (non‐depolarized) tissues.
Endogenous CA levels in the depolarized rat vasa deferentia fell to 67% of the controls after a 1 h incubation period and to 53% at the end of 2 hours.
Chromatographic separation on Amberlite CG‐120 columns of the newly synthesized CA and catechol metabolites from the rat vas deferens revealed that a very high proportion was present as dopamine. The percentage distribution after 1 h incubation in control Krebs‐Henseleit was: noradrenaline (NA): 30.6 ± 5.2; dopamine 56.9 ± 5.9; acid metabolites: 12.8 ± 1.1; and in KCl‐rich Krebs‐Henseleit, NA: 32; dopamine: 44.7 and acid metabolites 23.3. In contrast to the newly synthesized (14C‐labelled) CA, endogenous dopamine comprises only 10% of the endogenous CA stores in rat vas deferens.
The distribution of newly synthesized NA and dopamine in rat vas deferens is strikingly different from that of guinea‐pig vas deferens where more than 80% of newly formed amine is present as NA. In the latter tissue depolarization with K+ causes a striking increase in CA biosynthesis.
MECHANISM OF MECHANICAL INHIBITION OF SMOOTH MUSCLE BY OUABAIN
Authors: BOSE D. 
Published: July 2012

Ouabain (10 μg/ml) caused an initial increase followed by a decrease in tension in guinea‐pig taenia coli bathed in normal sodium and potassium containing medium.
The excitatory effect of ouabain was prevented by the elevation of extracellular potassium while the inhibitory effect was abolished in the absence of sodium in the bathing medium.
In the presence of sodium, the inhibitory effect of ouabain disappeared when the drug was washed out, but in the presence of lithium (which is not extruded by the Na‐K pump) the inhibition was not abolished.
The inhibitory effect of ouabain was accompanied by an increase in tissue Na and a decrease in tissue K concentration. The increase in intracellular [45Ca] which occurred when extracellular [K] was varied, was also reduced by ouabain.
It is concluded that a high intracellular level of sodium inhibits contractions in visceral smooth muscle probably by a mechanism involving decreased Ca influx.
A COMPARISON OF THE EFFECT OF MESCALINE ON ACTIVITY AND EMOTIONAL DEFAECATION IN SEVEN STRAINS OF MICE
Authors: LUSH I.E. 
Published: July 2012

Mescaline hemi‐sulphate (35 mg/kg body weight) was injected intraperitoneally into male mice (Mus musculus) from seven genetically diverse laboratory strains.
The effect of mescaline was found by comparison of the emotional defaecation and open field activity of mice after mescaline injection with the performance of the same mice after a subsequent saline (0.9% w/v NaCl solution) control injection.
In strains A2G, C3H/He, C57BR/cd, CBA/Cam and F/St, mescaline inhibited emotional defaecation and stimulated open field activity. These effects did not occur in strains ICFW and Schneider.
A positive relationship was found between the degree of emotional defaecation characteristic of each strain in the saline control experiment and the inhibitory effect of mescaline on emotional defaecation.
Pre‐treatment of mice with tranylcypromine (20 mg/kg body weight, i.p.) had no effect on emotional defaecation or on its inhibition by mescaline.