bluuebunny/crossref_metadata_2025_split huggingface dataset:
REVERSAL BY NALOXONE OF THE EFFECTS OF CHRONIC ADMINISTRATION OF DRUGS OF DEPENDENCE ON RAT LIVER AND BRAIN TRYPTOPHAN METABOLISM
Authors: BADAWY A. A.‐B. , EVANS M. , PUNJANI NAZEERA F. 
Published: July 2012

Chronic administration of ethanol, morphine, nicotine or phenobarbitone has previously been shown to enhance rat brain 5‐hydroxytryptamine (5‐HT) synthesis by increasing the availability of circulating tryptophan to the brain secondarily to the NADPH‐mediated inhibition of liver tryptophan pyrrolase activity
Naloxone reverses the above enhancement of 5‐HT synthesis and the accompanying increase in tryptophan availability to the brain and the inhibition of liver tryptophan pyrrolase activity
It is suggested that naloxone exerts these effects by antagonizing the chronic drug‐induced increase in liver [NADPH]
Naloxone increases serum corticosterone concentration in rats chronically treated with the above four drugs of dependence. Possible explanations of this effect are discussed.
A COMPARISON OF CARDIAC REACTIVITY AND β‐ADRENOCEPTOR NUMBER AND AFFINITY BETWEEN AORTA‐COARCTED HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: CERVONI PETER , HERZLINGER HELEN , LAI FONG M. , TANIKELLA TARAK 
Published: July 2012

The effects of noradrenaline (NA) and isoprenaline on isolated atria from aorta‐coarcted hypertensive rats (AHR) at early (6 day) and chronic (28 day) stages of hypertension were studied and compared with time‐matched, sham‐operated, normotensive rats (SNR). The number and affinity of β‐adrenoceptors ((−)‐[3H]‐dihydroalprenolol binding sites) were also studied in cardiac membranes prepared from these animals.
Six and 28 days after complete ligation of the abdominal aorta between the two renal arteries, rats became hypertensive with significantly greater arterial blood pressures than time‐matched SNR.
At both stages of hypertension, the atrial inotropic or chronotropic effects of NA and isoprenaline from hypertensive rats were similar to time‐matched SNR. Moreover, no differences in atrial reactivity were observed between the early and chronic stages of hypertension.
Irrespective of the stage of hypertension, cardiac membranes from the AHR contained the same number of β‐adrenoceptors as time‐matched SNR. In addition, the receptor affinity for the radioligand within each group was equivalent. However, the chronic stage hypertensive rats and their time‐matched controls contained fewer β‐adrenoceptors and these receptors had greater affinity for the radioligand when compared with cardiac membranes from rats at the early stage of hypertension and their controls.
The observed equivalent chronotropic and inotropic responses to NA and isoprenaline between the hypertensive and normotensive rats in both stages of hypertension may be explained in terms of similar receptor number and receptor binding affinity.
The reduced number of β‐adrenoceptors with greater binding affinity in day 28 normotensive or hypertensive rats may be a compensatory mechanism for these animals to maintain normal cardiac function with increasing age.
CHANGES IN SYNAPTOSOMAL HIGH AFFINITY CHOLINE UPTAKE FOLLOWING ELECTRICAL STIMULATION OF GUINEA‐PIG CORTICAL SLICES: EFFECT OF ATROPINE AND PHYSOSTIGMINE
Authors: ANTONELLI T. , BEANI L. , BIANCHI C. , PEDATA F. , PEPEU G. 
Published: July 2012

Superfused guinea‐pig cortical slices were electrically stimulated at different frequencies and the changes in acetylcholine (ACh) content measured. Synaptosomes were prepared at the end of the stimulation period and high affinity choline uptake (HACU) rate was measured.
The effect of increasing KC1 concentrations was compared on ACh content of the slices and on synaptosomal HACU.
Electrical stimulation (2, 5, 10, 20 Hz) elicited a frequency‐dependent linear increase in synaptosomal HACU rate and a decrease in ACh content of the slices.
The addition of atropine (1.5 × 10−8m) to the slices enhanced and that of physostigmine (3 × 10−5 m) reduced the frequency‐dependent increase in HACU rate. Atropine (1.5 × 10−6 m) not only antagonized the effect of physostigmine, but the HACU rate measured after treatment with both drugs was larger than that found after atropine alone.
These results indicate that in the cortical cholinergic nerve endings, depolarization caused by electrical stimulation is coupled with an increase in choline transport which can be modulated by the addition of atropine or physostigmine. Furthermore, within given experimental conditions a linear relationship exists between the reciprocal of ACh content in the slices and synaptosomal HACU.
SHAPE CHANGES INDUCED BY BIOLOGICALLY ACTIVE PEPTIDES AND NERVE GROWTH FACTOR IN BLOOD PLATELETS OF RABBITS
Authors: GUDAT FRED , LAUBSCHER ANDREAS , OTTEN UWE , PLETSCHER ALFRED 
Published: July 2012

Nerve growth factor (NGF), substance P (SP) and thymopoietin all caused shape change reactions of rapid onset in rabbit platelets. NGF had the highest maximal effect, and SP the lowest EC50 (concentration causing half maximal shape change). The action of SP was reversible within 5 min, whereas that of NGF lasted for at least 1 h. A series of other peptides were inactive.
After preincubation of platelets with SP, a second application of SP no longer caused a shape change reaction, whereas the effect of NGF was not influenced.
An oxidized NGF‐derivative without biological activity did not cause a shape change reaction, neither did epidermal growth factor.
Prostaglandin E1 (PGE1) and pretreatment of the platelets with 3% butanol, which counteract the shape changes caused by 5‐hydroxytryptamine (5‐HT) and adenosine 3′, 5′‐diphosphate, also antagonized those induced by NGF and SP. Neither heparin nor methysergide, an antagonist of 5‐HT‐receptors, influenced the shape change induced by NGF or SP. The action of NGF was also antagonized by a specific antibody to NGF.
Thymopoietin, like the basic polypeptide polyornithine (mol. wt. 40,000), was not antagonized by PGE1 and butanol. Heparin, which counteracted the effect of polyornithine, did not influence that of thymopoietin.
In conclusion, different modes of action are involved in the shape change of blood platelets induced by polypeptides and proteins. SP and NGF may act by stimulating specific membrane receptors.
SYMPATHETIC MECHANISMS IN DIET‐INDUCED THERMOGENESIS: MODIFICATION BY CICLAZINDOL AND ANORECTIC DRUGS
Authors: ROTHWELL NANCYJ. , STOCK M.J. , WYLLIE M.G. 
Published: July 2012

The sympathetic noradrenergic activation of brown adipose tissue and the biochemical mechanisms involved in diet‐induced thermogenesis were studied in rats.
A close correlation was found between brown adipose tissue Na+, K+‐adenosinetriphosphatase (Na+, K+‐ATPase) activity in vitro and in vivo measurements of resting oxygen consumption (VO2). The effects of noradrenaline on in vitro Na+, K+‐ATPase activity in brown adipose tissue and in vivo VO2 could be mimicked by a variety of agents. These included β‐adrenoceptor agonists and agents known to induce the release of noradrenaline or inhibit the noradrenaline uptake process. The pharmacological evidence suggests that dopaminergic mechanisms may also be involved in the control of thermogenesis.
3 Amphetamine did not increase VO2 in rats without causing associated increases in locomotor activity. Ciclazindol at doses of 3–30 mg/kg intraperitoneally increased VO2 but did not appear to increase locomotor activity or evoke any other signs of CNS stimulation including lengthening of time to sleep onset or stereotypy. Separation of metabolic and CNS effects occurred only at the lowest dose of mazindol used (0.3 mg/kg i.p.)‐ These results are probably a reflection of (a) the relative abilities of these drugs to inhibit brain and brown adipose noradrenaline uptake processes and (b) the relatively high accumulation of ciclazindol in brown adipose.
Of the drugs tested, only ciclazindol was a more potent inhibitor of the noradrenaline uptake system in brown adipose tissue (BAT) than in brain. Kinetic analysis also revealed that the actions of ciclazindol on the NA uptake system and Na+, K+‐ATPase in BAT differed from those of mazindol.
These findings suggest that ciclazindol may produce an energy wasting effect in rodents without causing overt CNS stimulation; the implications of these findings in terms of human obesity are discussed.
STIMULATION OF PROSTACYCLIN RELEASE FROM THE EPICARDIUM OF ANAESTHETIZED DOGS
Authors: DUSTING G.J. , NOLAN R.D. 
Published: July 2012

The generation of prostanoids in the hearts of anaesthetized dogs was studied by irrigating in situ the epicardial surface with Krebs solution. Prostanoids were measured by direct bioassay on smooth muscles and by radioimmunoassay of 6‐oxo‐prostaglandin F1α (6‐oxo‐PGF1 α) and prostaglandin E2 (PGE2) in the epicardial irrigation fluid.
The epicardial irrigation fluid contained a prostacyclin‐like substance, as indicated by the bioassay tissues, and immunoreactive 6‐oxo‐PGF1α; PGE2‐like materials were also detected. By both methods the output of the prostacyclin‐like substance, which decreased with time of epicardial irrigation, was increased by manipulating the heart and by adding arachidonic acid (3 μg/ml), and decreased by adding indomethacin (1 μg/ml) to the irrigating fluid.
Bioassayed prostacyclin and immunoreactive 6‐oxo‐PGF1α in the epicardial irrigation fluid increased by about 3‐5ng/ml during and after infusion of isoprenaline (0.1 μg kg−1 min−1). The substance was not released by isoprenaline when indomethacin was added to the irrigating fluid, or when propranolol (0.5 mg/kg) was given intravenously.
Aortic constriction, bilateral carotid artery occlusion and intravenous angiotensin infusion all increased output of the prostacyclin‐like substance into the epicardial irrigation fluid. The output was abolished by treating the heart with indomethacin (10 mg/kg intravenously or 1 μg/ml epicardially).
The prostacyclin‐like substance was also released by all of the above stimuli after the parietal pericardium had been removed and replaced by a plastic sheet.
It is concluded that prostacyclin is continually released from tissues close to the epicardial surface and from the pericardium, and that prostacyclin generation increases when cardiac workload increases. Prostacyclin of epicardial or pericardial origin might therefore contribute to metabolic regulation of coronary blood flow.
A STUDY ON THE ACUTE EFFECT OF AMPHETAMINE ON THE URINARY EXCRETION OF BIOGENIC AMINES AND METABOLITES IN MONKEYS
Authors: CHUANG LIN‐WHEI , KAROUM FAROUK , PERLOW MARK J. 
Published: July 2012

The effects of an acute dose (3mg/kg) of amphetamine on the urinary excretion of phenylethylamine (PEA), p‐tyramine, their metabolites, catecholamine metabolites and p‐hydroxymandelic acid, a major metabolite of p‐octopamine were evaluated in the monkey. Amphetamine excretion was also measured.
Amphetamine was slowly eliminated from the body, being found in the urine at least six days after administration.
Amphetamine increased the excretion of PEA and decreased that of its major metabolite, phenylacetic acid (PAA). This pattern of changes is similar to that previously found in the urine of chronic schizophrenics.
The excretion of the dopamine metabolite, 3,4‐dihydroxphenylacetic acid (DOPAC) was markedly reduced, that of vanilmandelic acid (VMA) remained unchanged while 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) was increased on the day of drug administration and persisted for at least a further six days. A similar extended effect on the excretion of p‐hydroxymandelic acid (it was reduced) was also observed.
The excretion of p‐tyramine but not its metabolite, p‐hydroxyphenylacetic acid, was decreased by amphetamine during treatment and returned to normal levels six days later.
From the results obtained, it was concluded that amphetamine effects on behaviour cannot exclusively be attributed to its influence on catecholamines and that other biogenic amines may be involved. 7 Since PEA elicits many behavioural changes similar to those seen with amphetamine, and since amphetamine increases PEA excretion, we suggest that amphetamine may exert some of its behavioural responses through the release of PEA.
ACTIVATION OF CENTRAL MUSCARINIC RECEPTORS CAUSES RESPIRATORY STIMULATION IN CONSCIOUS ANIMALS
Authors: WEINSTOCK MARTA 
Published: July 2012

Oxotremorine (10 μg/kg) injected intravenously into conscious rabbits pretreated with atropine‐methyl‐nitrate (ATMN, 0.5 mg/kg) caused significant increases in respiration rate from 94 to 131 per min, and in Pao2 from 13.8 to 15.4 kPa, and a decrease in Paco2 from 3.30 to 2.09 kPa within 15 min. Blood pH fell from 7.44 to 7.16.
Blood pressure increased by 11.6%, 5 min after oxotremorine injection.
The acidosis was shown to be due to an increase in blood lactic acid from 41 to 132 mg/100 ml.
Pretreatment with propranolol (5 mg/kg, s.c.) prevented the lactic acidosis and fall in pH but did not alter the respiratory stimulation induced by oxotremorine.
It is suggested that the lactic acidosis induced by oxotremorine results from stimulation of β‐adrenoceptors in skeletal muscle by catecholamines released from the adrenal medulla and sympathetic nerves.
Since all the above effects of oxotremorine are antagonized by hyoscine (5 mg/kg) but not by ATMN (0.5 mg/kg), it is concluded that oxotremorine can stimulate respiration by a direct action on muscarinic receptors in the central nervous system.
BENZODIAZEPINES REDUCE GASTRIC ULCERS INDUCED IN RATS BY STRESS
Authors: FILE SANDRA E. , PEARCE JACALYN B. 
Published: July 2012

The sedative and antiulcer effects of chlordiazepoxide (5 to 50 mg/kg) and lorazepam (0.25 to 2.5 mg/kg) were investigated in the rat.
Sedation was measured by recording locomotor activity in a holeboard. Ulceration of the glandular stomach was induced by a 2 h period of restraint at 4°C.
Acutely, both drugs produced significant sedation at all doses; high doses only (chlordiazepoxide 10 and 50 mg/kg; lorazepam 2.5 mg/kg) produced a significant reduction in ulcer formation.
With chronic treatment, after 5 and 10 days administration of chlordiazepoxide (50 mg/kg), tolerance to sedation was observed without a similar change in antiulcer action.
Cimetidine (20 mg/kg) and atropine (0.2 mg/kg) decreased ulcer formation without causing sedation.
The antisecretory profile of chlordiazepoxide (2 × 10−4m), in the rat isolated gastric mucosa, resembled that of atropine (10−7 m) rather than cimetidine (10−5 m).
These observations suggest that the antiulcer effect of benzodiazepines probably results from a combination of sedative, anxiolytic and antisecretory actions.
ANTIGEN‐INDUCED BRONCHIAL ANAPHYLAXIS IN ACTIVELY SENSITIZED GUINEA‐PIGS: EFFECT OF LONG‐TERM TREATMENT WITH SODIUM CROMOGLYCATE AND AMINOPHYLLINE
Authors: ANDERSSON PER , BERGSTRAND HÅKAN 
Published: July 2012

The effects of long‐term treatment with sodium cromoglycate (SCG) and aminophylline on antigen‐induced bronchoconstriction have been studied in guinea‐pigs actively sensitized according to two different regimens (one producing IgE‐ and IgG‐like antibodies and the other producing exclusively IgG‐like antibodies).
Treatment for three weeks with SCG (10 mg/kg) and aminophylline (10,30 or 60 mg/kg) led to a decreased bronchial response capacity which persisted even three days after treatment ceased. In this respect SCG was effective only in guinea‐pigs sensitized to produce at least partly IgE‐like antibodies; aminophylline was effective in guinea‐pigs sensitized to produce both IgE and/or IgG antibodies.
The results in vivo with SCG were reflected in vitro by a reduced capacity of chopped lung tissue to release histamine at antigen challenge; lungs from animals treated with aminophylline did not show reduced histamine releasing capacity.
Acute treatment with atropine was shown to reduce significantly the antigen‐induced bronchial contraction in guinea‐pigs sensitized to produce both IgE‐ and IgG‐antibodies. No effect of atropine was seen on an IgG‐mediated anaphylaxis.
Increased reactivity to methacholine but not to histamine was seen in guinea‐pigs sensitized to produce both IgG‐ and IgE‐antibodies. Long‐term treatment with SCG did not affect this hyperreactivity to methacholine.
Decreased reactivity to isoprenaline was found in isolated tracheae taken from guinea‐pigs sensitized to produce both IgE‐ and IgG‐like antibodies compared to unsensitized guinea‐pigs. Long‐term treatment with SCG, but not with aminophylline, reversed this decreased reactivity.
In vivo RECEPTOR BINDING OF THE OPIATE PARTIAL AGONIST, BUPRENORPHINE, CORRELATED WITH ITS AGONISTIC AND ANTAGONISTIC ACTIONS
Authors: DUM JANE E. , HERZ ALBERT 
Published: July 2012

In order to gain more insight into the mechanisms behind the actions of opiate partial agonists, an analysis of the dual agonist/antagonist properties of the partial agonist, buprenorphine, was made in conjunction with in vivo binding studies of the drug in the rat.
Buprenorphine revealed a bell‐shaped dose‐response curve for antinociception peaking at approx. 0.5 mg/kg subcutaneously. It antagonized morphine antinociception at doses which normally have agonistic effects and produced maximum antagonistic effects at doses above those having prominent agonistic activity. The withdrawal precipitating potency of buprenorphine as measured in highly morphine‐dependent rats was present at doses above those having agonistic activity. The entire dose‐response curve for buprenorphine was shifted symmetrically to the right by the opiate antagonist, naltrexone.
The dose‐dependent occupation of receptors in vivo by buprenorphine seemed to be almost complete over the agonist dosage range; almost no further receptor occupation over the antagonist range was seen.
The possibility is discussed that site‐to‐site receptor interactions leading to cooperativity of effect may be the best explanation of these results.
FACILITATION BY CLONIDINE OF PURINE RELEASE INDUCED BY HIGH KC1 FROM THE RABBIT PULMONARY ARTERY
Authors: KATSURAGI TAKESHI , SU CHE 
Published: July 2012

The effect of clonidine on the 3H‐purine release evoked by KC1 or (−)‐adrenaline was assessed in the superfused helical strip of the rabbit pulmonary artery pretreated with [3H]‐adenosine.
Clonidine (3 × 10−5 M to 10−4 m) significantly enhanced the 3H‐purine efflux evoked by 50 mM KC1 but not by 3 × 10−6M (−)‐adrenaline.
This facilitatory effect of clonidine on the KCl‐induced purine release was unaltered by phentolamine 3 × 10−6M. It was absent in arterial segments denervated with 6‐hydroxydopamine 30 jig/ml.
A sustained contractile response was evoked by clonidine 3 × 10−5 M without an increase in the 3H‐purine efflux. This was significantly reduced by phentolamine 3 × 10−6 M, but not by yohimbine 10−5M or by denervation with 6‐hydroxydopamine. 5 The uptake of [3H]‐adenosine into the segments was not inhibited by clonidine 3 × 10−5 M.
It is suggested that the facilitation by clonidine of the KCl‐induced purine release is due to prevention of presynaptic autoinhibition of purine release from adrenergic nerves, by an anti‐adenosine action of the drug.
AN ANALYSIS OF FUNCTIONAL ANTAGONISM AND SYNERGISM
Authors: MACKAY DENNIS 
Published: July 2012

A method is described for deriving null equations for functional antagonism and synergism. These null equations relate together the concentrations of agonist required to produce equivalent states of a cell or tissue in the presence and in the absence of a functional interactant
In one particular case the null equation leads to conclusions which are very similar to those reached by an earlier author who did not use the null method. However, the null equations give a clearer insight into the quantitative aspects of functional interaction.
It is concluded that the use of functional antagonism to estimate affinity constants and relative intrinsic efficacies of agonists has serious limitations. On the other hand, it may be possible to use the null equations, or similar principles, to test the validity of postulated mechanisms and sites of action of functional interactants.
INCREASED CENTRAL 5‐HYDROXTRYPTAMINE RECEPTOR MECHANISMS IN RATS AFTER CHRONIC NEUROLEPTIC TREATMENT
Authors: DAWBARN D. , LONG S.K. , PYCOCK C.J. 
Published: July 2012

The behavioural responses of drugs known to act through central 5‐hydroxytryptamine (5‐HT) mechanisms have been investigated in rats receiving a neuroleptic (trifluoperazine) in their drinking water for 4 to 6 months.
5‐Hydroxytryptophan (5‐HTP) induced 5‐HT‐dependent behaviours including head bobbing and lateral head weaving, reciprocal forepaw treading, tremor, backward walking, body writhing and ‘wet‐dog’ shakes. In doses of 50 to 150 mg/kg, 5‐HTP induced more intense behavioural effects in neuroleptic‐treated rats than in the control animals.
Similarly the putative 5‐HT agonist, quipazine (1 to 20 mg/kg) and the 5‐HT releasing drug, fenfluramine (5 to 20 mg/kg), both induced significantly greater motor responses in the chronically neuroleptic‐treated rats.
A 5‐HT uptake inhibitor (femoxetine, 2.5 to 10 mg/kg) had little behavioural effect in either control or trifluoperazine‐treated rats.
Total specific high‐affinity binding of radiolabeled 5‐HT was significantly increased in crude membrane fractions prepared from the cortex, striatum and substantia nigra of neuroleptic‐treated rats compared to control animals.
High‐affinity uptake of radiolabeled 5‐HT into striatal slices was similar in experimental and control animals.
Behavioural and biochemical data would indicate that postsynaptic 5‐HT mechanisms are enhanced in rats treated chronically with trifluoperazine. Chronic neuroleptic therapy may thereby induce cerebral 5‐HT receptor supersensitivity in addition to the well‐documented cerebral dopamine receptor supersensitivity.
THE EFFECTS OF THE SUBCUTANEOUS INJECTION OF THE CRUDE VENOM OF THE AUSTRALIAN COMMON BROWN SNAKE, Pseudonaja textilis ON THE SKELETAL NEUROMUSCULAR SYSTEM
Authors: HARRIS J.B. , MALTIN C.A. 
Published: July 2012

The effects of the crude venom of the Australian common brown snake on the mammalian neuromuscular system have been investigated.
The venom was injected subcutaneously into the dorso‐lateral aspect of one hind limb of the rat. The limb was paralysed within 90 min and remained paralysed for 2 to 3 days.
The exposed muscles failed to respond to indirect excitation, and individual fibres were not depolarized at the nerve‐muscle junction by exposure to carbachol.
The wet weight, histological appearance, resting potential and input resistance of the muscle fibres and their ability to generate directly elicited action potentials were unaffected by exposure to the venom.
Administration of venom to isolated preparations caused a reduction in the amplitude of miniature endplate potentials, with no change in frequency. The quantal content of evoked endplate potentials was unchanged.
It was concluded that the crude venom was largely devoid of presynaptic activity and myotoxicity, and that its primary site of neurotoxicity was directed to the postsynaptic membrane.