bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANTAGONISM OF 5‐HYDROXYTRYPTAMINE RECEPTORS BY QUIPAZINE
Authors: LANSDOWN M.J.R. , NASH H.L. , PRESTON P.R. , WALLIS D.I. , WILLIAMS R.G. 
Published: July 2012

The antagonist actions of quipazine on 5‐hydroxytryptamine (5‐HT) receptors have been investigated in the rabbit isolated superior cervical ganglion and on the rat isolated spinal cord and stomach strip.
Changes in membrane potential induced by 5‐HT or by the nicotinic agonist, 1,1‐dimethyl‐4‐phenyl piperazinium (DMPP), were measured in the ganglion by the sucrose‐gap technique. At ganglionic receptors, quipazine had little or no agonist activity, but greatly depressed depolarizations evoked by 5‐HT but not depolarizations evoked by DMPP or trimethylammonium (TMA). Injections into the superfusion stream to the ganglion of 2 to 5 μmol quipazine in a small volume of Krebs solution prevented all subsequent responses to 5‐HT. Superfusion of the ganglion with quipazine at a concentration of 1 μm produced complete blockade of responses to 5‐HT in 3 of 6 ganglia and reduced responses by over 90% in 2 others; responses to DMPP were potentiated in amplitude and duration. Superfusion at a concentration of 0.1 μm depressed responses to 5‐HT by 75% on average. The threshold concentration for the blocking action was around 0.01 μm, which depressed responses by 42% on average in 6 experiments (range 0 to 75%).
5‐HT (1 μm or 100 μm) depressed the amplitude of the dorsal root potentials recorded from the isolated, hemisected cord of the neonate rat by 27 ± 5% (mean ± s.e. mean, n = 14) and by 45 ± 6% (n = 14), respectively. In the presence of quipazine (0.01 μm), 5‐HT (1 μm or 100 μm) depressed the amplitude by 6 ± 2% (n = 15) and by 3 ± 1% (n = 7), respectively.
Concentration‐response curves of the contractions induced by 5‐HT in the fundus of the rat stomach were obtained in the absence and presence of quipazine. Quipazine (1 μm) shifted the concentration‐response curve to the right and depressed the maximum, suggesting a non‐competitive mode of antagonism. pI50 values were calculated in order to assess the antagonist activity of quipazine at rat fundus 5‐HT receptors; the mean pI50 was 6.91 ± 0.2 (n = 6).
It is concluded that quipazine may be an effective antagonist at 5‐HT receptors in various tissues.
A DEMONSTRATION OF NALOXONE‐PRECIPITATED OPIATE WITHDRAWAL ON SINGLE NEURONES IN THE MORPHINE‐TOLERANT/DEPENDENT RAT BRAIN
Authors: FRY J.P. , HERZ A. , ZIEGLGÄNSBERGER W. 
Published: July 2012

A comparison has been made between the effects of microelectrophoretically applied naloxone on single neurones in the frontal cerebral cortex and the striatum of naive and of morphine‐tolerant/dependent rats, anaesthetized with a mixture of α‐chloralose and urethane.
Specificity of the results obtained was evaluated by contrasting the effects of alternate applications of the (+)‐ and (−)‐isomers of naloxone to the same neurones.
In naive rats naloxone had predominantly no effect, only a few cells revealing non‐specific depressant responses to the drug.
In morphine‐tolerant/dependent rats a higher proportion of neurones responded to naloxone; either with stereospecific excitatory responses, in which the activity evoked by l‐glutamate or acetylcholine was increased, or with a non‐specific inhibition, similar to that observed in naive animals.
It is suggested that these excitatory responses to microelectrophoretically applied (−)‐naloxone represent opiate withdrawal responses at the single neurone level and that they reflect a latent hyperexcitability of the postsynaptic membrane in the morphine‐tolerant/dependent state.
THE SYNOVIAL PROSTAGLANDIN SYSTEM IN CHRONIC INFLAMMATORY ARTHRITIS: DIFFERENTIAL EFFECTS OF STEROIDAL AND NONSTEROIDAL ANTI‐INFLAMMATORY DRUGS
Authors: BOMBARDIERI S. , CATTANI P. , CIABATTONI1 G. , DI MUNNO O. , PASERO G. , PATRONO C. , PINCA E. , PUGLIESE F. 
Published: July 2012

The present study was undertaken to characterize the spectrum of arachidonic acid metabolites present in synovial effusions of patients with rheumatoid or psoriatic arthritis, and to compare changes in their concentration following a short‐term treatment with 6α‐methyl‐prednisolone (6‐MeP: 4–8mg/day) or indoprofen (1.2g/day), a nonsteroidal anti‐inflammatory agent with proven synovial prostaglandin inhibitory effect.
Measurements of prostaglandin E2 (PGE2), thromboxane (TX) B2, 6‐keto‐PGF1α and PGF2α were performed by radioimmunoassay techniques in synovial effusions obtained from 23 patients, and validated by thin‐layer chromatographic analysis of the extracted immunoreactivity.
PGE2 and TXB2 accounted for more than 60% of the total immunoreactivity in untreated patients. The absence of any constant ratio between the different arachidonic acid metabolites detected in synovial fluid is consistent with a heterogeneous cellular origin of these compounds.
Indoprofen treatment was associated with a consistent reduction of synovial prostaglandin and thromboxane concentrations, ranging from 36% in the case of 6‐keto‐PGF1α to 90% in the case of PGE2.
In contrast, 6‐MeP caused opposite changes on different metabolites originating via the cyclo‐oxygenase pathway. Thus, 6‐keto‐PGF1α concentrations were reduced by 35%, PGF2α concentrations were increased by 30%, while PGE2 and TXB2 were unchanged following 6‐MeP.
Although the mechanism(s) underlying the failure of 6‐MeP to reduce synovial PGE2 and TXB2 levels are uncertain, the results of the present study clearly indicate that therapeutic doses of steroidal and nonsteroidal anti‐inflammatory drugs cause quite distinct changes in arachidonic acid metabolism, which might be relevant to their specific therapeutic actions and side‐effects.
CHARACTERIZATION OF THE RAT PAROTID β‐ADRENOCEPTOR
Authors: CARLSÖÖ BENGT , DANIELSSON ÅKE , HENRIKSSON ROGER , IDAHL LARS‐ÅKE 
Published: July 2012

The effects of various β‐adrenoceptor agonists on amylase secretion from the rat parotid gland were studied by means of two different in vitro techniques.
The dose‐response relation for each agonist was established, as also were the ED50 values.
All drugs appeared to act directly on the acinar cells, as reserpine‐treatment did not abolish their secretagogic effects.
Two groups of agonists could be distinguished: one group consisting of adrenaline, noradrenaline and the β1‐selective agonist prenalterol (H133/22) with a high enzyme discharge potency and a second group consisting of the β2‐agonists, terbutaline and salbutamol, with a markedly lower effect.
The present data further support the theory that rat parotid acinar cells are supplied mainly with β‐adrenoceptors of the β1‐subtype, similar to those present in heart and adipose tissue.
THE EFFECT OF MELANOTROPHIN RELEASE INHIBITING FACTOR (MIF) AND CYCLO (LEU‐GLY) ON THE TOLERANCE TO MORPHINE‐INDUCED ANTINOCICEPTION IN THE RAT: A DOSE‐RESPONSE STUDY
Authors: BHARGAVA HEMENDRA N. 
Published: July 2012

The effects of melanotrophin release inhibiting factor (MIF) and its cyclic analogue cyclo (Leu‐Gly) on tolerance to the analgesic effect of morphine were studied in male Sprague‐Dawley rats.
Tolerance to morphine was induced by implantation of four morphine pellets (each containing 75 mg of morphine free base) during a 3 day period.
Daily subcutaneous administration of MIF and cyclo (Leu‐Gly) before and during the morphine pellet implantation inhibited the development of tolerance to morphine analgesia. The minimum daily dose of the peptides required to produce a significant effect was 0.5 mg/kg.
The effects of single injections of MIF and cyclo (Leu‐Gly) on morphine tolerance revealed that the minimum doses of cyclo (Leu‐Gly) and MIF to inhibit morphine tolerance were 4 and 8 mg/kg, respectively.
Chronic treatment with morphine resulted in an enhanced hypothermic response to a dopamine agonist, apomorphine. The enhancement of this response was blocked by both MIF and cyclo (Leu‐Gly) in doses that inhibited morphine tolerance.
It is concluded that MIF and cyclo (Leu‐Gly) block the development of analgesic tolerance as well as dopamine receptor hypersensitivity induced by chronic morphine treatment and the two phenomena may be interrelated.
THE EFFECT OF A XANTHINE DERIVATIVE, 1‐(5′OXOHEXYL)‐3‐METHYL‐7‐PROPYLXANTHINE (HWA 285), ON HEART PERFORMANCE AND REGIONAL BLOOD FLOW IN DOGS AND RABBITS
Authors: HUDLICKA O. , KOMAREK J. , WRIGHT A.J.A. 
Published: July 2012

The effect of a new xanthine derivate 1–5′ oxohexyl‐3‐methyl‐7‐proplyxanthine (HWA 285) was studied on heart performance in dogs and rabbits and on regional blood flow in rabbits.
Heart performance (cardiac output and dP/dt max) in dogs was increased. Cardiac work (calculated as CO x mean BP) was not changed in dogs and did not change or was slightly decreased in rabbits. Heart rate was increased in dogs and unchanged in rabbits.
Blood pressure decreased slightly in dogs, and more markedly in rabbits. Total peripheral resistance was decreased in both species.
Regional blood flow (studied by use of 15 μm labelled microspheres) was increased in the heart, brain and skeletal muscle; the increase was dose‐dependent in the range 0.3, 1.0 and 3.0 mg HWA 285 per kg intravenously. The highest dose produced a 2 fold decrease in the peripheral resistance in the brain, a 2.5 fold decrease in the heart and 4 fold decrease in skeletal muscle.
The drugs preferentially dilated small (7 to 10 μm) rather than larger (12 to 17 μm) arterioles; 9 μm microspheres were found in the outflowing blood after application of the drug, and the calculated blood flow increases were smaller, or absent, as compared with values obtained with 15 μm microspheres.
EVIDENCE AGAINST THE INVOLVEMENT OF PROSTAGLANDINS IN THE VASOCONSTRICTOR ACTION OF CALCIUM ION IN RAT MESENTERIC BLOOD VESSELS
Authors: COUPAR I.M. 
Published: July 2012

Prostaglandin E2 (PGE2) has been claimed to be essential to the vasoconstrictor action of noradrenaline in rat mesenteric blood vessels. Since noradrenaline acts by releasing intracellular calcium, experiments have been performed using the perfused rat superior mesenteric artery preparation to determine whether prostaglandin synthesis is necessary for the direct vasoconstrictor action of calcium
The cyclo‐oxygenase inhibitors, indomethacin and 5, 8, 11, 14‐eicosatetraynoic acid (ETA), inhibited responses to noradrenaline and calcium but both were less effective in inhibiting the response to calcium than to noradrenaline
PGE2 (6 ng‐20 μg/ml) failed to overcome the inhibitory effect of indomethacin (62 μg/ml) and ETA (10 μg/ml) on the response to the EC50 of Ca2+ (100 μg/ml). The EC50 of Ca2+ did not significantly increase PGE2‐like release by the blood vessels from the resting value of 19 ± 8pg of PGE2 equivalents/min
PGA1 (6 μg/ml) and the thromboxane A2 agonist, U‐46619 (200ng/ml), both caused full restoration of indomethacin‐depressed responses to calcium, but did not restore responses depressed by ETA. U‐46619 (200ng/ml) also reversed the inhibitory effect of papaverine (4 μg/ml) and caused a 1.6 fold potentiation of Ca2+ responses
The results do not support the hypothesis that prostaglandin synthesis is essential to the vasoconstrictor action of Ca2+ in rat mesenteric blood vessels.
SELECTIVE ACETYLENIC ‘SUICIDE’ AND REVERSIBLE INHIBITORS OF MONOAMINE OXIDASE TYPES A AND B
Authors: KALIR A. , SABBAGH A. , YOUDIM M.B.H. 
Published: July 2012

A number of aromatic‐N‐propargyl (acetylenic) compounds and indoleamines were tested for their inhibitory action on monoamine oxidase (MAO) type A and type B using the substrates 5‐hydroxytryptamine (5‐HT), β‐phenylethylamine (PEA) and dopamine.
Structure activity studies with aromatic‐N‐propragyl (acetylenic) derivatives have shown that MAO inhibitory potency is least dependent on the aromatic portion of the compounds. N‐methylated propargyl derivatives are the most active and replacement of the methyl group with a higher alkyl or aromatic group results in significant reduction of activity. The triple bond in the N‐propargyl portion is absolutely essential for activity and must be β‐to the nitrogen. It is the acetylenic group that gives these compounds their irreversible MAO inhibitory property.
The present study has indicated that since the acetylenic compounds resemble the enzyme substrates the distance between the aromatic ring and the N‐propargyl terminal is crucial in designating the type A or type B MAO inhibitory property. For MAO type A inhibition, a distance equivalent to at least three carbon units is required, while for the inhibition of the B type enzyme this distance can be 1 or 2 carbon units.
The compounds AGN‐1133 and AGN‐1135 show most promise in Parkinson's disease or as anti‐depressants because of their irreversible selective type B MAO inhibition in vitro and in vivo.
A number of indoleamine derivatives were found to be reversible selective type A inhibitors.
THE EFFECT OF HEAVY METAL CHELATORS ON THE RENAL ACCUMULATION OF PLATINUM AFTER cis‐DICHLORO‐DIAMMINEPLATINUM II ADMINISTRATION TO THE RAT
Authors: GRAZIANO JOSEPH , JONES BRIAN , PISCIOTTO PATRICIA 
Published: July 2012

Rats received a total of 18 mg/kg cis‐dichlorodiammineplatinum (II) (CDDP) intravenously and were treated concomitantly with calcium ‐disodium ethylenediaminetetraacetic acid (CaNa2EDTA), 2,3‐climercaptopropanol (BAL), deferoxamine, 2,3‐dimercaptosuccinic acid (DMS) or vehicle. In comparison to controls, renal platinum concentration was significantly reduced in the DMS and deferoxamine‐treated groups. However, significant deterioration occurred in the deferoxamine‐treated group. The hepatic platinum concentration was unaffected by the chelating agents.
Following a dose of 6 mg/kg CDDP intravenously, eight days of treatment with DMS, 50 mg/kg daily, had no effect on renal platinum excretion, while treatment with 100 or 200 mg/kg daily reduced renal platinum concentration by 50%.
In order to determine whether DMS could prevent the nephrotoxicity of CDDP, rats were given 6 mg/kg CDDP intravenously, followed by a four day course of DMS treatment at doses of 0,50,100 or 200 mg/kg daily begun 3 h after the CDDP dose. DMS failed to prevent renal toxicity as indicated by weight loss, serum creatinine concentration, renal histology, and the urinary excretion of N‐acetyl‐β‐glucosaminidase, a renal tubular enzyme.
RENAL VASODILATOR ACTIVITY OF PROSTAGLANDIN E2 IN THE RAT ANAESTHETIZED WITH PENTOBARBITONE
Authors: HAYLOR J. , TOWERS J. 
Published: July 2012

The effect of intra‐aortic administration (i.a.) of prostaglandin E2 (PGE2) on renal blood flow was studied in the rat anaesthetized with pentobarbitone. Renal blood flow was assessed in two ways, either by use of an electromagnetic flow probe or by measurement of the renal clearance of p‐aminohippurate (PAH).
PGE2 (0.1 μg/min, i.a.) increased renal blood flow measured by either method. However, PAH clearance overestimated the degree of vasodilatation compared to that obtained using the flow meter. The possibility that PGE2 or a metabolite may increase PAH extraction by the kidney was considered.
The sensitivity of the rat to the renal vasodilator actions of PGE2 was enhanced by using a flank retro‐peritoneal approach from which to insert the flow probe, rather than a mid‐line abdominal incision.
Dose‐response curves demonstrate that under the conditions used, PGE2 produced a biphasic change in renal vascular resistance, vasodilatation started at 0.01 μg/min and was maximal at about 3 μg/min, while at the highest dose used (20μg/min) PGE2 induced renal vasoconstriction.
The results indicate that contrary to previous reports, the rat does not exhibit an important species difference in the response of its renal vasculature to PGE2. Therefore, physiological and pathophysiological roles which have previously been attributed to vasoconstriction produced by PGE2 synthesized in the kidney may now have to be considered.
MECHANISMS OF ELEVATION OF RAT BRAIN TRYPTOPHAN CONCENTRATION BY VARIOUS DOSES OF SALICYLATE
Authors: BADAWY A. A.‐B. 
Published: July 2012

The roles of inhibition of liver tryptophan pyrrolase activity and of displacement of tryptophan from its binding sites on serum proteins have been investigated in relation to the increase in rat brain tryptophan concentration after administration of various doses of sodium salicylate.
The elevation of brain tryptophan concentration by sodium salicylate (0.5 mg/kg) was caused by inhibition of liver pyrrolase activity, whereas that by doses of the drug of 50 mg/kg and above was achieved mainly by tryptophan displacement. Both tryptophan displacement and pyrrolase inhibition caused the increase in brain tryptophan concentration by sodium salicylate at 10 mg/kg.
The smallest dose of salicylate capable of displacing serum‐protein‐bound tryptophan was 2.5 mg/kg.
REGIONAL RAT BRAIN BENZODIAZEPINE RECEPTOR NUMBER AND γ‐AMINOBUTYRIC ACID CONCENTRATION FOLLOWING A CONVULSION
Authors: BOWDLER JULIE M. , GREEN A. RICHARD 
Published: July 2012

Following administration to rats of an electroconvulsive shock (ECS) which resulted in a major tonic‐clonic seizure, no changes in [3H]‐diazepam binding characteristics were observed in cortex or hippocampus with either a well washed membrane preparation or a crude synaptosomal preparation.
No changes were observed in [3H]‐diazepam binding in any other brain region examined 30 min after an ECS.
Thirty min following an ECS, regional brain γ‐aminobutyric acid (GABA) concentrations increased in hippocampus, cortex and hypothalamus. Only in the hippocampus did the increase occur within 5 min of the seizure.
Similar increases in GAB A concentration were seen after a bicuculline‐induced seizure but not after a seizure induced by flurothyl; both treatments produced a tonic‐clonic seizure.
Pretreatment of the rats with (+)‐propranolol 5 min before the ECS abolished the tonic extension and prevented the brain GAB A concentration changes that occur 30 min after the seizure.
No increase in GABA concentration was seen in hippocampus, cortex or hypothalamus 30 min after the final ECS of a course of 10 ECS given once daily for 10 days. In contrast a marked increase in striatal GABA concentration was observed.
These changes in GABA biochemistry following a seizure are discussed in relation to the post‐ictal rise in seizure threshold that is occurring at the same time.
EEFECTS OF REPEATED LITHIUM ADMINISTRATION ON THE SUBCELLULAR DISTRIBUTION OF 5‐HYDROXYTRYPTAMINE IN RAT BRAIN
Authors: ATTERWILL C. K. , TORDOFF ANN F.C. 
Published: July 2012

The content and distribution of 5 ‐hydroxytryptamine (5‐HT) between subcellular fractions from rat whole brain (excluding cerebellum) were examined following repeated lithium administration.
Lithium chloride (3 mEq/kg body wt. s.c.) administered twice daily for 3 days produced no change in the 5‐HT content of primary subcellular fractions (P1—nuclear; P2—crude synaptosomal; SNT—soluble) measured on the 4th day.
Similarly, repeated lithium treatment alone did not appear to produce increases in the 5‐HT content of either cytoplasmic (S) or vesicular (M2) fractions derived from hypo‐osmotically disrupted synaptosomes (P2) when compared to control rats receiving NaCl only.
One hour after monoamine oxidase inhibition with tranylcypromine, there was a further selective 25% increase in 5‐HT accumulation in the lithium‐treated rats over control values in the soluble cytoplasmic fraction (S) and in fractions containing occluded cytoplasm only. This increase did not occur in the synaptic vesicle fraction (M2). This corresponds to an increase in 5‐HT turnover rate due to the lithium treatment of approx. 50%.
These findings lend additional support to the hypothesis that lithium treatment alters the intraneuronal storage or compartmentation of 5‐HT between vesicles and cytoplasm.
EFFECTS OF β‐ADRENOCEPTOR DRUG STIMULATION ON VARIOUS MODELS OF GASTRIC ULCER IN RATS
Authors: ESPLUGUES JUAN , LLORIS JOSÉ M. , MARTÍ‐BONMATÍ EZEQUIEL , MORCILLO ESTEBAN J. 
Published: July 2012

Experiments were designed to evaluate the effect of the pharmacological activation of β‐adrenoceptors on various models of gastric ulcer in the rat.
Pretreatment with the β‐adrenoceptor stimulant drugs, isoprenaline or salbutamol, significantly inhibited stress‐induced gastric ulcers. This anti‐ulcer effect was abolished by propranolol but not by atenolol, suggesting that β2‐adrenoceptors mediate this response.
In the pylorus‐ligation model, salbutamol inhibited lesion formation and reduced the intragastric content of hydrogen ions, histamine and pepsin although the latter was only affected with the higher dose of salbutamol.
Salbutamol also prevented the ulcerogenic action on the gastric mucosa of an exogenously perfused artificial gastric juice, showing that the anti‐ulcer effect is not necessarily dependent on acid inhibition.
Salbutamol also reduced the formation of acute ulcers induced by various iatrogenic means (histamine, polymyxin B, reserpine and indomethacin).
Long‐term treatment with salbutamol accelerated the healing of experimental chronic gastric ulcer.
In anaesthetized rats, salbutamol produced a dose‐related increase in mucosal blood flow which may contribute to its mode of action.
It is concluded that β‐adrenoceptor agonists exert preventive and curative effects on gastric damage induced in the rat. This effect seems specific and mediated through β‐adrenoceptor activation.
INHIBITION OF RAT LIVER TRYPTOPHAN PYRROLASE ACTIVITY AND ELEVATION OF BRAIN TRYPTOPHAN CONCENTRATION BY ACUTE ADMINISTRATION OF SMALL DOSES OF ANTIDEPRESSANTS
Authors: BADAWY A. A.‐B. , EVANS M. 
Published: July 2012

Administration to rats of a 0.5 mg/kg dose of any of 19 antidepressants, but not that of many other drugs, causes a significant inhibition of the total enzyme and apoenzyme activities of liver tryptophan pyrrolase (of 24–48% and 37–65% respectively) and elevates brain tryptophan concentration by 13–66%.
When liver tryptophan pyrrolase activity is enhanced by pretreatment with cortisol or haematin, subsequent administration of a 0.5 mg/kg dose of some, but not other, antidepressants causes inhibition, which is weak (up to 38%).
This weak inhibition of the enhanced pyrrolase activity together with other pharmacological and physiological factors could explain the time lag between the start of antidepressant medication and the occurrence of a therapeutic response.
The cortisol‐induced and haematin‐activated pyrrolases respond differentially to inhibition by imipramine and amitriptyline, and this may explain the differential response to these two drugs of depressed patients in relation to urinary excretion of the noradrenaline metabolite 3‐methoxy‐4‐hydroxyphenylglycol.
The results are discussed in relation to the mechanism of action of antidepressants and the possible involvement of disturbed hepatic tryptophan metabolism in depressive illness.
PERIPHERAL TOXICITY OF HEMICHOLINIUM‐3 IN MICE
Authors: FREEMAN J.J. , KOSH J.W. , PARRISH J.S. 
Published: July 2012

The site (i.e. peripheral or central) of the toxicity produced by hemicholinium‐3 in mice was investigated.
Hemicholinium‐3 was measured fluorometrically and acetylcholine was determined by gas chromatography after intraventricular or intraperitoneal administration of hemicholinium‐3.
Hemicholinium‐3 was not detected in the brain nor were acetylcholine levels decreased in the brain after systemic administration.
The dose‐response curve following intraventricular administration demonstrated that hemicholinium‐3 was not as lethal after central administration as it was after peripheral administration.
Approximately 24% of a 75 μg intraventricular dose of hemicholinium‐3 was found in the periphery at death.
These results suggest that hemicholinium‐3 manifests its toxicity primarily in the periphery.