bluuebunny/crossref_metadata_2025_split huggingface dataset:
A NON‐ADRENERGIC INHIBITORY NERVOUS PATHWAY IN GUINEA‐PIG TRACHEA
Authors: COLEMAN R.A. , LEVY G.P. 
Published: July 2012

Electrical stimulation of the guinea‐pig isolated tracheal tube causes a biphasic response, initially excitatory and then inhibitory. The excitatory response was abolished by atropine leaving the inhibitory response unaffected.
The inhibitory response was greatly reduced but not abolished by propranolol or guanethidine. A residual inhibitory response was still present in tracheas in which sympathetic nerve function had been abolished by pretreatment with syrosingopine or 6‐hydroxydopamine. These results show that the inhibitory response is predominantly adrenergic but that a small non‐adrenergic component is also present.
The non‐adrenergic inhibitory response was abolished by lignocaine and tetrodotoxin suggesting that it is nervous in origin.
Optimal stimulation parameters for the predominantly adrenergic inhibitory response were a pulse width of 0.7–2 ms, a stimulation period of 7 s and a frequency of 20 Hz. For the non‐adrenergic inhibitory response, optimal stimulation parameters were a pulse width of 2 ms, a stimulation period of 12 s and a frequency of 20 Hz.
Evidence obtained with pharmacological antagonists, enzyme inhibitors and activators suggested that the transmitter mediating the non‐adrenergic inhibitory nervous response is unlikely to be: acetylcholine, histamine, 5‐hydroxytryptamine, cyclic 3′,5′‐adenosine monophosphate or a prostaglandin.
The adenosine uptake blocking drugs dipyridamole, hexobendine and Dilazep potentiated the non‐adrenergic inhibitory nervous response and unmasked inhibitory responses to adenosine and adenosine 5′‐triphosphate.
It is concluded that electrical stimulation of the guinea‐pig trachea, in addition to activating cholinergic and adrenergic nervous pathways, may activate a separate and distinct inhibitory nervous pathway. This pathway has some features in common with the non‐adrenergic non‐cholinergic inhibitory pathways in gastro‐intestinal muscle.
GUANETHIDINE AND GUANACLINE ON THE RAT VAS DEFERENS
Authors: GERKENS J.F. 
Published: July 2012

In acute experiments guanethidine was considerably more potent than guanacline in reducing contractile responses of the rat vas deferens to electrical stimulation of intramural nerves.
Chronic treatment of rats for 19 weeks with guanethidine (5mg/kg, daily) reduced responses to electrical stimulation to 25% of control, potentiated responses to exogenous noradrenaline and depleted endogenous noradrenaline.
After cessation of guanethidine treatment responses to electrical stimulation increased to 60% of control (in one week) but showed no further increase. There was no decrease in the potentiation of exogenous noradrenaline (after 14 weeks) nor any increase in endogenous noradrenaline levels (after 7 weeks).
Chronic treatment of rats for 19 weeks with guanacline (5mg/kg, daily) potentiated responses to exogenous noradrenaline and depleted endogenous noradrenaline as much as guanethidine treatment but did not reduce responses to electrical stimulation.
On cessation of guanacline treatment there was some increase in noradrenaline content (after 2 to 3 weeks) and some decrease of potentiated responses to exogenous noradrenaline (after 2 weeks).
The noradrenaline‐depleting action of these drugs is distinct from blockade of nerve‐mediated responses in the rat vas deferens and contractile function after guanethidine treatment can be partly restored despite persistence of noradrenaline depletion and supersensitivity.
EVIDENCE FOR INVOLVEMENT OF 5‐HYDROXYTRYPTAMINE IN THE ACTIONS OF AMPHETAMINE
Authors: BREESE G.R. , COOPER B.R. , MUELLER R.A. 
Published: July 2012

Pargyline treatment, 1 h before (+)‐amphetamine (1 mg/kg), reduced amphetamine‐stimulated motor activity. This inhibition was reversed in animals pretreated with p‐chlorophenylalanine (PCPA).
Following treatment with PCPA or 5,6‐dihydroxytryptamine (5,6‐DHT), amphetamine‐induced locomotor activity was significantly potentiated. The increased response to amphetamine in PCPA‐treated rats was reversed in animals pretreated with 5‐hydroxytryptophan.
The inhibition of amphetamine‐stimulated locomotor activity by treatment with 6‐hydroxydopamine was not reversed by PCPA treatment.
Stereotypies produced by amphetamine were not found to be altered by depletion of 5‐hydroxytryptamine.
Induction of adrenal tyrosine hydroxylase activity produced by chronic amphetamine administration was significantly potentiated by PCPA, emphasizing the involvement of a 5‐hydroxytryptamine inhibitory system in more than one action of amphetamine.
CHANGES IN PLASMA KININOGEN LEVELS INDUCED BY CELLULOSE SULPHATE DURING PREGNANCY IN THE RAT
Authors: McCORMICK J.T. , SENIOR JUDITH , WHALLEY E.T. 
Published: July 2012

Cellulose sulphate (1 mg/kg) produced a 30–40% depletion of plasma kininogen in rats.
The time course of repletion of kininogen in the plasma was compared in rats in the oestrous and dioestrous stages of the cycle and in 22 day pregnant animals. A partial repletion occurred, 3 h after the cellulose sulphate injection, which was followed by a secondary fall in plasma kininogen. Plasma kininogen values were back to control levels 10 h after the treatment in all groups.
Treatment of rats from days 19–22 of pregnancy with cellulose sulphate resulted in 40% depletion of plasma kininogen and in prolongation of pre‐parturition behaviour.
It is suggested that the increase which normally occurs in plasma kininogen levels towards the end of pregnancy in the rat may play a role in the process of parturition.
STUDIES ON THE KINETICS OF [3 H]‐OUABAIN UPTAKE AND EXCHANGE IN THE ISOLATED PAPILLARY MUSCLE OF THE GUINEA‐PIG
Authors: LÜLLMANN H. , PETERS T. , RAVENS URSULA 
Published: July 2012

The uptake, wash‐out and exchange of [3 H]‐ouabain was studied in isolated, resting, and electrically stimulated papillary muscles of the guinea‐pig.
At the equilibrium level of uptake, a different tissue/medium ratio was obtained for each of the concentrations used, i.e. 3.4, 1.8 and 0.82 for 1 × 10−7 M, 7.7 × 10−7 M, and 5 × 10−6 M ouabain, respectively. Equilibrium was reached more rapidly at high concentrations of ouabain.
The maximum number of binding sites for ouabain was estimated to be 1 × 1015 binding sites/g wet weight.
No difference in [3 H]‐ouabain uptake could be detected between resting and electrically stimulated papillary muscles.
The kinetics of the ouabain uptake, wash‐out and exchange are discussed. The results suggest that there is a saturable compartment in papillary muscle which can best be demonstrated if low concentrations of ouabain are used. Because of its small size, the saturable compartment submerges in the process of the filling of the extracellular space at high concentrations (5 × 10−6 M).
INHIBITION OF 5‐HYDROXYTRYPTAMINE‐INDUCED HUMAN BLOOD PLATELET AGGREGATION BY CHLORPROMAZINE AND ITS METABOLITES
Authors: BOULLIN D.J. , GRAHAME‐SMITH D.G. , GRIMES R.P.J. , WOODS H.F. 
Published: July 2012

Blood platelets from normal human subjects were isolated and aggregated in vitro with adenosine diphosphate (ADP) or 5‐hydroxytryptamine (5‐HT).
The effects of chlorpromazine and 7 major metabolites upon 5‐HT‐induced aggregation were investigated.
All the phenothiazines inhibited 5‐HT‐induced aggregation when added to platelet rich plasma 3 min prior to 5‐HT.
There were no qualitative differences in the inhibitory effects, but inhibitory potency varied over a wide range. The decreasing order of potency was monodesmethylchlorpromazine, chlorpromazine, 7‐hydroxychlorpromazine, didesmethylchlorpromazine, 3,7‐dimethoxychlorpromazine, didesmethylchlorpromazine sulphoxide, chlorpromazine sulphoxide, chlorpromazine nitroxide.
INVESTIGATION OF THE VASODILATOR AND ANTISECRETORY ROLE OF PROSTAGLANDINS IN THE RAT GASTRIC MUCOSA BY USE OF NON‐STEROIDAL ANTI‐INFLAMMATORY DRUGS
Authors: MAIN I.H.M. , WHITTLE B.J.R. 
Published: July 2012

The effects of non‐steroidal anti‐inflammatory drugs on gastric acid secretion and mucosal blood flow were studied in the rat.
Indomethacin, in ulcerogenic doses, caused a dose‐dependent rise in pentagastrin‐stimulated acid secretion, but decreased mucosal blood flow per unit acid secretion.
During resting conditions, indomethacin had no significant effect on acid output, but reduced mucosal blood flow.
Pretreatment with indomethacin, phenylbutazone or meclofenamate potentiated the secretory response to dibutyryl cyclic adenosine 3′,5′‐monophosphate.
Indomethacin markedly reduced the mucosal prostaglandin‐like activity at a time when mucosal erosion formation had reached steady levels.
These results provide evidence that prostaglandins have a local role in the regulation of blood flow and acid secretion in the rat gastric mucosa, and suggest that non‐steroidal anti‐inflammatory drugs cause mucosal erosions by disrupting these processes.
LIVER AND BRAIN TRYPTOPHAN METABOLISM FOLLOWING HYDROCORTISONE ADMINISTRATION TO RATS AND GERBILS
Authors: GREEN A. R. , SOURKES T.L. , YOUNG S.N. 
Published: July 2012

Liver tryptophan pyrrolase activity is low in the mongolian gerbil (Meriones unguiculatus) and is not induced by hydrocortisone (5 mg/kg). In contrast, there is measurable activity in the rat liver and this is induced by hydrocortisone. In vivo measurements confirmed the absence of induction in gerbils but suggested that they were able to metabolize tryptophan. However, no detectable pyrrolase activity was found in any other tissues either before or after hydrocortisone.
In agreement with previous observations hydrocortisone decreased rat brain 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) 6 h after administration. Brain tryptophan concentrations were also decreased at this time. In contrast, hydrocortisone did not alter gerbil brain 5‐HT, 5‐HIAA or tryptophan. α‐Methyltryptophan activated hepatic tryptophan pyrrolase and decreased brain 5‐HT and 5‐HIAA in both animals.
Results suggest that the decrease in rat brain 5‐HT and 5‐HIAA following hydrocortisone may be associated with the rise in liver tryptophan pyrrolase and that the brain amine changes are mediated through the decrease in brain tryptophan concentration.
THE EFFECTS OF HYPERCHOLESTEROLAEMIC PLASMA ON VASCULAR SENSITIVITY TO NORADRENALINE
Authors: BLOOM D. , McCALDEN T.A. , ROSENDORFF C. 
Published: July 2012

The pressor responses to injected noradrenaline (NA) of 42 isolated perfused femoral arteries of the rabbit were studied.
Potentiation of the responses was found when hypercholesterolaemic plasma was perfused through the arteries. No change was found with normal plasma.
Potentiation of the responses was found when isolated β‐lipoprotein in Krebs solution was perfused. No change was found with similar amounts of bovine albumen.
Pure cholesterol dissolved directly into normal plasma, and dissolved via propanol into Krebs solution or plasma caused no potentiation. Propanol alone in Krebs or plasma had no effect.
Potentiation was caused by a decreased equilibrium coefficient (Keq) for the NA‐adrenoceptor interaction and an increased maximal pressor response (Rmax).
It is concluded that cholesterol carried on its apoprotein is capable of potentiating the pressor effects of noradrenaline.
ELECTROCONVULSIVE SHOCK INCREASES THE BEHAVIOURAL RESPONSES OF RATS TO BRAIN 5‐HYDROXYTRYPTAMINE ACCUMULATION AND CENTRAL NERVOUS SYSTEM STIMULANT DRUGS
Authors: EVANS JANE P.M. , GRAHAME‐SMITH D.G. , GREEN A.R. , TORDOFF ANN F.C. 
Published: July 2012

A single electroconvulsive shock (ECS) of 150 V for 1 s increased the concentration of rat brain 5‐hydroxyindoleacetic acid (5‐HIAA) but did not alter brain 5‐hydroxytryptamine (5‐HT) or tryptophan concentrations 3 h later.
A single ECS decreased 5‐HT synthesis 3 h and 6 h later. Synthesis was back to normal after 24 hours. The ECS‐treated rats did not show greater hyperactivity produced by the increased brain 5‐HT accumulation following administration of l‐tryptophan and tranylcypromine at any time up to 24 h later. This suggests that a single electroshock does not alter 5‐HT functional activity.
Twenty‐four hours after the final ECS of a series of 10 shocks given once daily, the rats were given tranylcypromine and l‐tryptophan. They displayed greater hyperactivity than control rats not treated with ECS, suggesting that ECS increased 5‐HT functional activity. Brain concentrations of 5‐HT, 5‐HIAA and tryptophan were then unchanged by ECS. 5‐HT synthesis and accumulation of 5‐HT following tranylcypromine and l‐tryptophan were not altered by ECS.
The hyperactivity following administration of the 5‐HT agonist 5‐methoxy N,N‐dimethyltryptamine was enhanced by repeated (10 day) ECS, suggesting altered post‐synaptic responses to 5‐HT receptor stimulation.
Repeated ECS enhanced locomotor activity following tranylcypromine and l‐DOPA. It did not alter brain noradrenaline or dopamine concentrations.
The latent period before a pentylenetetrazol‐induced convulsion was shortened by repeated ECS.
Following repeated ECS there appears to be increased neuronal sensitivity to certain stimuli producing centrally mediated behavioural stimulation. This is discussed in relation to the mechanism by which electroconvulsive therapy (ECT) produces its therapeutic effect.
INFLAMMATORY EFFECTS OF PROSTAGLANDIN D2 IN RAT AND HUMAN SKIN
Authors: FLOWER R.J. , HARVEY E.A. , KINGSTON W.P. 
Published: July 2012

Intradermal injection of prostaglandin (PG) D1 and D2 in the human forearm produced a long‐lasting dose‐related erythema. When compared with prostaglandin E1 or E2 the order of potency for erythema production was PGE1 > PGE2 > PGD2 > PGD1.
In rat skin, prostaglandin D2 but not D1 caused an increase in vascular permeability as quantitated by the Evans blue method and the 125I‐albumin extravasation technique. Prostaglandin E2 was 3–5 times more potent than prostaglandin D2.
Prostaglandin D2 (10 ng) potentiated the increase in vascular permeability in rat skin produced by histamine, but not that produced by bradykinin.
Prostaglandin D2 (10, 20 and 50 ng) did not elicit oedema or hyperalgesia in the rat paw oedema test, but potentiated carrageenan‐induced oedema; hyperalgesia was potentiated by doses of 100 ng and above.
EMETINE MYOPATHY IN THE RAT
Authors: BRADLEY W.G. , FEWINGS J.D. , HARRIS J.B. , JOHNSON MARGARET A. 
Published: July 2012

(–)‐Emetine (0.25‐2.0 mg/kg i.p.) was administered to rats for up to 220 days.
At doses of 1.0 mg/kg or less, the animals continued to gain weight but more slowly than the untreated control animals. The physiological changes in the muscles from these animals were minimal; there was a small reduction in both the resting membrane potential and in the maximum rate of rise of the action potential. There was no atrophy or loss of muscle fibres although in the occasional muscle, hyaline fibres, necrotic fibres and split fibres were observed. There was a focal loss of myofibrillar adenosine triphosphatase (ATPase) and nicotinamide adenine dinucleotide tetrazolium reductase (NADH‐TR) in Type II and Type III fibres, but no such loss in Type I fibres.
The animals receiving 2.0 mg/kg of (–)‐emetine gained weight slowly for up to 20 days but then rapidly lost weight and by 30 days they were weak and emaciated. The muscles from these animals were severely atrophied and the total muscle wet weight was reduced by almost 20%.
The strength of the muscles from these animals was measured in vitro using direct stimulation. They were weaker than normal both in absolute terms and when expressed in terms of tension developed/unit wet weight.
There was no evidence of either functional or structural denervation but surgically denervated muscles from animals in this group were indistinguishable from denervated muscles from normal rats.
Severe structural damage was obvious in the fibres of both extensor digitorum longus and soleus. Necrotic, hyaline and splitting fibres were common and the focal loss of myofibrillar ATPase and NADH‐TR activity was extensive and occurred in Type I fibres as well as in Type II and Type III fibres.
It is concluded that the muscular weakness induced by (–)‐emetine is due to a direct effect on the muscle fibres and that this occurs at a subcellular level. There is no evidence that functional or structural denervation plays any role in the aetiology of emetine myopathy in the rat.
GLUTAMATE ANTAGONISTS IN RAT HIPPOCAMPUS
Authors: SEGAL M. 
Published: July 2012

Hippocampal cellular responses to acidic amino acids and some of their antagonists were measured in the rat anaesthetized with urethane. The effects of these antagonists on the field responses of the rat hippocampus to afferent stimulation were measured in acute as well as chronically prepared rats.
Hippocampal pyramidal cells were excited by microiontophoretic application of glutamate and aspartate. These responses were antagonized by glutamic acid diethyl ester (GDEE), glutamic acid dimethyl ester (GDME) and by proline. Partial specificity could be seen as excitatory responses to acetylcholine were less susceptible to the antagonists.
Field responses of the hippocampus to commissural stimulation were reduced significantly in both an acutely prepared or the conscious rat following parenteral administration of GDEE and GDME but not proline. Responses to perforant path stimulation were not affected by these drugs.
It is suggested that an acidic amino acid may serve as a neurotransmitter in the commissural path to area CA1 of the dorsal hippocampus.
EFFECT OF INDOMETHACIN AND RELATED DRUGS ON THE CALCIUM ION‐DEPENDENT SECRETION OF LYSOSOMAL AND OTHER ENZYMES BY NEUTROPHIL POLYMORPHONUCLEAR LEUCOCYTES In vitro
Authors: NORTHOVER B.J. 
Published: July 2012

1Rabbit isolated peritoneal neutrophil polymorphonuclear leucocytes were depleted of calcium by exposure for 1 h to calcium‐free bathing fluid at 4°C.2Addition of calcium ions to the previously calcium‐depleted cells during incubation at 37°C stimulated the release of β‐glucuronidase and of lysozyme but not of lactate dehydrogenase.3Low concentrations of indomethacin, flufenamate or salicylate, such as those which occur in the blood plasma after therapeutic doses of these drugs, selectively inhibited the calcium‐induced release of β‐glucuronidase. The slight release of this enzyme which occurred in the absence of added calcium ions was not altered by these drugs, neither was the release of lactate dehydrogenase.4Release of lysozyme was inhibited by low concentrations of salicylate, amidopyrine or oxyphen‐butazone, independent of the presence or absence of calcium ions.5Chloroquine, hydrocortisone or colchicine did not alter the release of leucocyte enzymes.
VASOCONSTRICTOR RESPONSE TO ARACHIDONIC ACID IN THE ISOLATED HIND LIMB OF THE DOG
Authors: FITZPATRICK T.M. , JOHNSON M. , KOT P.A. , RAMWELL P.W. , ROSE J.C. 
Published: July 2012

1Arachidonic acid (AA) (25‐200 μg/kg) produced a dose‐related increase in perfusion pressure in dog isolated hind limbs perfused with either blood or a platelet‐free perfusate.2Prostaglandin E2 produced vasodilatation while prostaglandin produced no vascular change at these administered doses.3Phentolamine did not alter the arachidonic acid response, eliminating possible α‐adrenoceptor mediation.4Aspirin and indomethacin blocked the vasoconstrictor response to AA.5This study indicates that a vasoactive intermediate in prostaglandin synthesis can be elaborated in the absence of platelets.
DOPAMINE‐INDUCED NEUROGENIC VASODILATATION IN THE INTACT HINDLEG OF THE DOG
Authors: BOGAERT M.G. , DE SCHAEPDRYVER A.F. , WILLEMS J.L. 
Published: July 2012

1The dopamine‐induced neurogenic vasodilatation, previously described in the isolated perfused hindleg of the dog, has been studied in anaesthetized dogs with intact circulation in the hindleg. Dopamine was administered intravenously and/or intra‐aortically, either as a bolus injection of 4 or 16 μg/kg, or as a continuous infusion of 4, 8, 16 or 32 μg kg−1 min−1.2Dopamine, given as a bolus injection or by infusion, reversibly inhibited synaptic transmission in the paravertebral lumbar ganglia, studied with preganglionic stimulation at 1 Hz. The inhibitory effect decreased gradually when the frequency of stimulation was increased to 16 Hz. The inhibition by dopamine was also present when spontaneous postganglionic activity was recorded. These effects were more pronounced on intra‐aortic than on intravenous administration of dopamine.3In about half of the animals studied, injection or infusion of dopamine elicited a decrease of vascular resistance in the innervated femoral artery, whereas systemic blood pressure either did not change or decreased. In the denervated femoral artery, an increase in vascular resistance was always observed.4The decrease in femoral vascular resistance was considered to correspond with neurogenic vasodilatation caused by paravertebral ganglionic inhibition since (i) it only occurred in the innervated hindleg, (ii) blood pressure did not rise, (iii) this decrease was insensitive to atropine or propranolol and (iv) it was blocked by small doses of haloperidol. When hypovolemic shock was produced, the incidence of the neurogenic decrease of vascular resistance was smaller.5Dopamine also increased renal blood flow. This increase was not reduced by the occurrence of the neurogenic vasodilatation in the innervated femoral artery.6These results are consistent with the idea that the dopamine‐induced neurogenic vasodilatation, originally described in the isolated perfused hindleg of the dog, also occurs when the circulation to the hindleg is intact. This suggests that, in the dog, the inhibitory effect of dopamine on sympathetic ganglia modulates its peripheral vasoconstrictor effects. In hypovolemic shock, where sympathetic nervous activity is high, the inhibitory effect of dopamine on sympathetic ganglia disappears and its direct vasoconstrictor effect on the vessels dominates.