bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF AMINOPHYLLINE ON TRYPTOPHAN AND OTHER AROMATIC AMINO ACIDS IN PLASMA, BRAIN AND OTHER TISSUES AND ON BRAIN 5‐HYDROXYTRYPTAMINE METABOLISM
Authors: CURZON G. , FERNANDO J.C.R. 
Published: July 2012

Aminophylline and other methylxanthines increase brain tryptophan and hence 5‐hydroxytryptamine turnover. The mechanism of this effect of aminophylline was investigated.
At lower doses (≯ 100 mg/kg i.p.) the brain tryptophan increase could be explained by the lipolytic action of the drug, i.e. increased plasma unesterified fatty acid freeing plasma tryptophan from protein binding so that it became available to the brain.
Plasma unesterified fatty acid did not increase when aminophylline (100 mg/kg i.p.) was given to nicotinamide‐treated rats but as both plasma total and free tryptophan rose, a tryptophan increase in the brain still occurred.
The rise in brain tryptophan concentration following the injection of a higher dose of the drug (150 mg/kg i.p.) could no longer be explained by a rise of plasma free tryptophan as the ratio of brain tryptophan to plasma free tryptophan rose considerably. Plasma total tryptophan fell and the plasma insulin concentration rose.
The increase of brain tryptophan concentration after injection of 150 mg/kg aminophylline appeared specific for this amino acid as brain tyrosine and phenylalanine did not increase. However as their plasma concentrations fell the brain/plasma ratio for all three amino acids rose.
The higher dose of aminophylline increased the muscle concentration of tryptophan but that of tyrosine fell and that of phenylalanine remained unaltered. The liver concentrations were not affected.
The aminophylline‐induced increases of the ratio of brain tryptophan to plasma free tryptophan no longer occurred when the drug was given to animals injected with the β‐adrenoceptor blocking agent propranolol or the diabetogenic agent streptozotocin.
The changes in brain tryptophan upon aminophylline injection may be explained by (a) increased availability of plasma tryptophan to the brain due to increased lipolysis and (b) increased effectiveness of uptake of tryptophan by the brain due to increased insulin secretion.
EFFECT OF IONIZING RADIATION ON PROSTAGLANDIN‐LIKE ACTIVITY IN TISSUES
Authors: EISEN V. , WALKER D.I. 
Published: July 2012

One to 7 days after whole body exposure of mice to a single dose of 700 R of x‐rays, little or no change was detected in prostaglandin‐like activity in the brain, blood and seminal vesicles. Slight increases in intestinal and renal tissue were not significant. In the lung, mean activity rose from 62 ng/g to a transient peak of 145 ng/g wet weight on the fourth day (P > 0.05). In the spleen, mean levels rose steadily from 13.2 ng/g to 259 ng/g on the fourth day (P < 0.01), and were still 184.4 ng/g on the seventh day.
Prostaglandin‐like activity was measured 4 days after single doses of 200–700 R. In the lung, a significant rise was produced by 600 and 700 R, and in the spleen by 200–700 R.
Thin layer chromatography showed that part of the prostaglandin‐like activity in spleen extracts had an RF similar to that of [3H]‐prostaglandin E1, and part to that of [3H]‐prostaglandin F2α.
Splenic tissue from mice exposed to 700 R four days earlier, inactivated prostaglandin E1 less potently than did tissue from non‐irradiated mice.
IS THE CONTRACTILE RESPONSE TO EXOGENOUS ACETYLCHOLINE DUE TO A PRESYNAPTIC EFFECT?
Authors: LEE C.Y. , TSAI M.C. 
Published: July 2012

Whether the contractile response induced by exogenous acetylcholine (ACh) chiefly involved the pre‐or post‐synaptic junctional site of the motor endplate was studied by using the cat gastrocnemius nerve muscle preparation poisoned with β‐bungarotoxin (β‐BuTX), a toxin isolated from the venom of Bungarus multicinctus which acts presynaptically.
After neuromuscular transmission was completely blocked by β‐BuTX, the dose‐response curve of the contractile response induced by close intra‐arterial injection of ACh, was compared with that of the control. No appreciable difference was observed.
In contrast, the response to ACh was completely abolished when neuromuscular transmission was blocked by α‐bungarotoxin, a toxin isolated from the same venom which acts postsynaptically.
It is concluded that postjunctional site of the motor end‐plate is chiefly involved in the contractile response produced by exogenous ACh.
THE EFFECT OF NON‐STEROIDAL ANTI‐INFLAMMATORY DRUGS ON ADENOSINE TRIPHOSPHATE CONTENT AND HISTAMINE RELEASE FROM RAT PERITONEAL CELL SUSPENSIONS RICH IN MAST CELLS
Authors: CHAMPION G.D. , DAY R.O. , RAY J.E. , WADE D.N. 
Published: July 2012

Non‐steroidal anti‐inflammatory drugs (NSAID) suppressed compound 48/80‐induced histamine release from rat peritoneal cells in vitro in a dose‐dependent manner.
NSAID suppressed the adenosine triphosphate (ATP) content of rat peritoneal cells in vitro and this correlated strongly with the suppression of compound 48/80‐induced histamine release.
The correlation demonstrated suggests that the mechanism of action of NSAID in the rat peritoneal cells is via depletion of cellular ATP.
EFFECT OF p‐BROMOPHENACYL BROMIDE, AN INHIBITOR OF PHOSPHOLIPASE A2, ON ARACHIDONIC ACID RELEASE AND PROSTAGLANDIN SYNTHESIS BY THE GUINEA‐PIG UTERUS in vitro
Authors: MITCHELL SHEILA , POYSER N.L. , WILSON N.H. 
Published: July 2012

The synthesis of prostaglandins F2α and E2 by guinea‐pig uterine homogenates was inhibited by p‐bromophenacyl bromide (PBPAB), an inhibitor of phospholipase A2.
Metabolism of prostaglandin F2α by uterine homogenates was undetectable; this was not affected by PBPAB.
There was no significant difference between the amounts of arachidonic acid released from uterine homogenates on days 7 and 15 of the oestrous cycle. Small amounts of dihomo‐γ‐linolenic acid were detected in the homogenates.
The release of arachidonic acid from uterine homogenates was greatly inhibited by PBPAB.
Addition of exogenous arachidonic acid to uterine homogenates did not overcome the inhibition of uterine prostaglandin F2α synthesis produced by PBPAB.
It is concluded that PBPAB inhibits both the release of arachidonic acid from the guinea‐pig uterus and its subsequent conversion into prostaglandins.
EFFECT OF HARMALINE ON SODIUM TRANSPORT IN Rana esculenta SKIN
Authors: EHRENFELD J. , GARCIA‐ROMEU F. 
Published: July 2012

Harmaline, together with certain hallucinogenic alkaloids of the same group (harmine, 2 methyl harmine) stimulates sodium transport across the in vitro skin of Rana esculenta when it is added to the external medium at a low concentration (0.1 mm). This effect is due to an increase of the sodium influx, and is reversed by washing. It is suggested that harmaline intervenes at the sodium penetration sites at the external face of the transport compartment.
At a higher concentration (5 mm) added to the internal medium harmaline inhibits sodium net absorption. The inhibition is due mainly to an increase of the efflux, while the influx may be either inhibited or increased. Under these conditions the influx becomes insensitive to amiloride. It is suggested that the inhibition of sodium transport is the result of harmaline interfering with a transport ATPase, and also that harmaline induces new sites for the passage of sodium.
INTERACTION OF COCAINE WITH CHLORDIAZEPOXIDE ASSESSED BY MOTOR ACTIVITY IN MICE
Authors: D'MELLO G. , STOLERMAN I.P. 
Published: July 2012

Effects of a range of doses of cocaine and chlordiazepoxide given separately and as mixtures were determined on the spontaneous locomotor activity of mice.
Cocaine increased locomotor activity (walking) during 3 or 5 min trials in a dose‐related manner.
Chlordiazepoxide had little effect on the total amount of locomotor activity except for depression at very high doses. A lower dose of chlordiazepoxide increased activity at the beginning of the trials only.
Mixtures containing certain doses of cocaine and chlordiazepoxide increased locomotor activity to a much greater extent than cocaine alone. This high level of activity was manifested throughout 5 min trials.
This action of cocaine is similar to that of amphetamine.
EVIDENCE FOR DOPAMINE DEAMINATION BY BOTH TYPE A AND TYPE B MONOAMINE OXIDASE IN RAT BRAIN in vivo AND FOR THE DEGREE OF INHIBITION OF ENZYME NECESSARY FOR INCREASED FUNCTIONAL ACTIVITY OF DOPAMINE AND 5‐HYDROXYTRYPTAMINE
Authors: GREEN A.R. , MITCHELL B.D. , TORDOFF ANN F.C. , YOUDIM M.B.H. 
Published: July 2012

1 Tranylcypromine (20 mg/kg) administration to rats totally inhibited brain monoamine oxidase (MAO) oxidation of 5‐hydroxytryptamine (5‐HT), phenylethylamine and dopamine as measured in vitro. When l‐3,4‐dihydroxyphenylalanine (l‐DOPA) (50 mg/kg) was given 30 min after the tranylcypromine, brain dopamine and noradrenaline concentrations rose markedly and the rats displayed characteristic behavioural changes and locomotor activity.2 Clorgyline (5 mg/kg) administration inhibited 5‐HT oxidation by almost 100% but phenylethylamine by only 29% while (‐)‐deprenil (5 mg/kg) injection almost totally inhibited phenylethylamine oxidation and inhibited 5‐HT metabolism by only 31%. Administration of l‐DOPA after pretreatment with either drug did not alter brain dopamine or noradrenaline concentrations and the animals did not display any behavioural changes.3 Administration of clorgyline plus (‐)‐deprenil (5 mg/kg of each) almost totally inhibited oxidation of both phenylethylamine and 5‐HT; there was a large rise of brain dopamine and noradrenaline concentrations and the animals displayed the behavioural changes observed when tranylcypromine and l‐DOPA had been given.4 The effects of tranylcypromine (20 mg/kg) on brain 5‐HT, dopamine and noradrenaline concentrations up to 48 h after injection were recorded. Brain 5‐HT concentrations were considerably elevated for 18 h after injection and then fell steadily. In contrast, brain dopamine concentrations rose slightly and remained at this level for 48 h while noradrenaline levels doubled and also remained at this level for 48 hours.5 When l‐tryptophan (50 mg/kg) was given at various times after tranylcypromine the characteristic hyperactivity syndrome appeared at 12 h but not 18 h after tranylcypromine and a further rise in brain 5‐HT was only observed at 12 hours. When l‐DOPA (50 mg/kg) was given at various times after tranylcypromine a further large rise in brain dopamine and noradrenaline occurred at 12 h but not at 18 h and all the behavioural changes were observed only at 12 hours.6 Measurement of MAO activity at the above times after tranylcypromine showed that the half‐life of recovery of the enzyme activity with 5‐HT and dopamine as substrates was 4.5 days and 8.5 days with phenylethylamine as substrate. Inhibition of MAO oxidation of dopamine and 5‐HT was approximately 85%, 18 h after tranylcypromine injection.7 It is concluded from both the studies with clorgyline and deprenil and the recovery of MAO activity after tranylcypromine, that dopamine is metabolized by both Type A and Type B MAO in vivo and that it is only when both forms are almost totally inhibited that there is an increase in dopamine and 5‐HT functional activity, as judged by the appearance of the hyperactivity syndromes.
A POTENT NEW β2‐ADRENOCEPTOR BLOCKING AGENT
Authors: IMBS J.L. , MIESCH F. , SCHWARTZ J. , VELLY J. , LECLERC G. , MANN A. , WERMUTH C.G. 
Published: July 2012

1 (t‐Butyl‐amino‐3‐ol‐2‐propyl) oximino‐9 fluorene is a new β2‐adrenoceptor blocking agent with a pA2 of 9.23 ± 0.25 on isolated trachea.2 It provokes hypertension in normotensive rats and does not prevent arterial hypertension in SHR rats, although it does prevent the renin secretion normally induced by isoprenaline infusion.
CHARACTERIZATION OF (±)‐METHADONE UPTAKE BY RAT LUNG
Authors: CHI C.H. , DIXIT B.N. 
Published: July 2012

By use of a sensitive and specific fluorescence assay procedure it was shown that after subcutaneous administration to rats, (±)‐methadone was concentrated in the lung. Lung to serum ratios ranging from 25 to 60 were obtained indicating that the rat lung tissue was capable of extracting (±)‐methadone against a concentration gradient.
This phenomenon was investigated in vitro with rat lung slices incubated in Krebs‐Ringer phosphate buffer (pH 7.4). The uptake was expressed in terms of tissue to medium concentration ratios (T/M ratio).
The principal observations were: (i) Studies on the time‐course of the uptake showed that the T/M ratios of (±)‐methadone increased rapidly during the first 60 min of incubation and then more slowly, with a plateau occurring at 180 min; (ii) The T/M ratio of (±)‐methadone progressively increased from 9.5 to 17 as the pH of the incubation medium was varied from 6.2 to 7.8; (iii) When the concentration of (±)‐methadone in the incubation medium was varied from 0.005 to 0.5 mM, the T/M ratio decreased rapidly suggesting self‐saturation of the transport process. Beyond the medium concentration of 0.5 mM, the T/M ratio declined very slowly.
These results suggested that at low concentrations, (±)‐methadone was transported predominantly by a self‐saturable process while at higher concentrations it was transported by a process of simple diffusion.
At low concentrations (0.01 mM) the uptake of (+)‐methadone was higher than that of (‐)‐isomer indicating stereo‐specificity of the uptake process. The uptake of (±)‐methadone at low concentration (0.01 mM) was significantly inhibited by low temperature, lack of O2, lack of glucose, lack of Na+ in the incubation medium, and by exposure of the tissue to high temperature (≅100°C). The uptake was also inhibited by relatively high concentration of iodoacetate (1.0 mM) and of naloxone (1.0 mM).
Kinetic analysis of data showed that the diffusion constant for (±)‐methadone was 5.0 (h−1) and the Vmax of the active transport process was 6.5 μmol g−1 h−1.
THE INFLUENCE OF GASTRIC EMPTYING ON PLASMA CONCENTRATIONS OF THE ANALGESIC, MEPTAZINOL
Authors: FRANKLIN R.A. 
Published: July 2012

The influence of gastric emptying on the rate of absorption and peak plasma concentrations of meptazinol was studied in monkeys by comparison of the plasma concentrations of the drug achieved after intragastric and intraduodenal administration of the compound. Absorption was much more rapid and plasma concentrations were very much higher after intraduodenal than after intragastric dosage.
Determination of the ‘normal’ gastric emptying time in rats and monkeys showed that this was much longer in the monkey than in the rat. In addition, meptazinol was shown to have a pronounced retarding action on gastric emptying in the monkey, an effect which was not apparent in the rat.
The significance of these observations in relation to the species difference in oral potency of the drug is discussed.
CATECHOL‐SUBSTITUTED PHENOXY‐PROPANOLAMINES: ADRENOCEPTOR ACTIVITY IN THE ANAESTHETIZED CAT
Authors: DOWD H. , KEH G.S. , RAPER C. 
Published: July 2012

The pharmacological actions of racemic noradrenaline, adrenaline, isoprenaline and N‐t‐butylnoradrenaline have been compared with those of their corresponding derivatives containing an oxymethylene (OXY) link between the ring and ethanolamine side chain.
The compounds were tested in the anaesthetized cat for their ability to produce positive chronotropic effects, bronchodilator actions, changes in perfusion pressure in the perfused hind limb and decreases in soleus muscle contractions.
In comparison with the parent compounds, the OXY‐derivatives of adrenaline and noradrenaline had very weak α‐adrenoceptor stimulant effects.
THE ROLE OF β‐ADRENOCEPTORS IN THE RESPONSES OF THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG TO PHENYLEPHRINE, ISOPRENALINE, NORADRENALINE AND ADRENALINE
Authors: RICHARDSON P.D.I. , WITHRINGTON P.G. 
Published: July 2012

The sympathetically‐innervated hepatic arterial vascular bed of the dog was perfused from a femoral artery. Hepatic arterial blood flow and perfusion pressure were recorded continuously, and the hepatic arterial vascular resistance (HAVR) calculated from these measurements.
Intra‐arterial injections of phenylephrine caused dose‐dependent rises in HAVR, indicating hepatic arterial vasoconstriction, at all doses above threshold. No secondary reductions in HAVR followed these responses.
Intra‐arterial injections of isoprenaline caused only dose‐dependent reductions in HAVR at doses above threshold.
Intra‐arterial injections of noradrenaline typically caused an initial increase in HAVR which was followed at all but the highest doses by a secondary, delayed, reduction in HAVR.
Intra‐arterial injections of adrenaline, like those of noradrenaline, resulted in hepatic arterial vasoconstriction followed by hepatic arterial vasodilatation.
On a molar basis, the most potent hepatic arterial vasoconstrictor was noradrenaline, followed by adrenaline and phenylephrine.
The maximum reductions in HAVR caused by adrenaline (mean reduction = 21.9%) and noradrenaline (16.9%) were significantly smaller than those due to isoprenaline (P < 0.001).
Propranolol attenuated the hepatic arterial vasodilator responses due to isoprenaline, and the secondary falls in HAVR following intra‐arterial adrenaline and noradrenaline.
Propranolol did not modify the vasoconstrictor responses to phenylephrine.
Both adrenaline and noradrenaline were more potent hepatic arterial vasoconstrictors after propranolol than in the absence of β‐adrenoceptor blockade. The potentiation of the vasoconstrictor effects of adrenaline was statistically significant.
After propranolol, adrenaline was a more potent hepatic arterial vasoconstrictor than noradrenaline.
Since the β‐adrenoceptors in the hepatic arterial vasculature were not blocked by atenolol, but were stimulated by salbutamol, it is concluded that they are predominantly of the β2‐type.
The vasoconstrictor actions of phenylephrine, noradrenaline and adrenaline were all antagonized by the systemic administration of phentolamine, all three dose‐response curves being shifted to the right.
The results are discussed with regard to the possible control of the hepatic arterial vasculature by naturally‐occurring catecholamines.
MODIFICATION, BY ASPIRIN AND INDOMETHACIN, OF THE HAEMODYNAMIC AND PROSTAGLANDIN RELEASING EFFECTS OF E. coli ENDOTOXIN IN THE DOG
Authors: FLETCHER J.R. , RAMWELL P.W. 
Published: July 2012

Dogs treated with aspirin (10 mg/kg) or indomethacin (1.5 mg/kg) 45 min before, and 3 h after, an LD50 dose (1 mg/kg) of E. coli endotoxin were alive 72 h later.
Although all dogs in both treated groups survived, only those treated with indomethacin were protected against the fall in blood pressure 1–2 min following endotoxin.
Endotoxin increased the level of prostaglandin F2α in both the mixed venous and arterial blood. No increase was observed in the aspirin and indomethacin‐treated groups.
Aspirin and indomethacin treatment did not modify thrombocytopaenia or blood coagulation parameters following endotoxin.
EFFECTS OF 3‐METHYLINDOLE IN CATTLE
Authors: ATKINSON G. , BOGAN J.A. , BREEZE R.G. , SELMAN I.E. 
Published: July 2012

Rapid intravenous injection of 3‐methylindole (3‐MI) was shown to induce an anaphylactoid‐like reaction in calves.
This was suggested by the reduction in response to a repeat dose of 3‐MI, by the reduction of effects in the presence of antagonists to the putative mediators of anaphylaxis in cattle and by the production of signs similar to those seen in experimentally induced bovine anaphylaxis.
The plasma half‐life of 3‐MI was short (14.4 min) and, since absorption of 3‐MI from the rumen is known to be slow, the extent of formation of 3‐MI from L‐tryptophan in the rumen would have to be substantial if 3‐MI is to be considered the causative agent of ‘fog fever’, an acute respiratory distress syndrome seen in cattle.
EFFECTS OF MIANSERIN, A NEW ANTIDEPRESSANT, ON THE in vitro AND in vivo UPTAKE OF MONOAMINES
Authors: GOODLET I. , MIREYLEES S.E. , SUGRUE M.F. 
Published: July 2012

The effects of mianserin and of selected tricyclic antidepressants were compared in a number of monoamine uptake models.
The ability of mianserin to block the noradrenergic neurone membrane amine pump of rabbit brain stem slices was comparable to that of imipramine and amitriptyline and less than that of desipramine and nortriptyline. Both mianserin and desipramine were competitive inhibitors of noradrenaline uptake in vitro. The effect of mianserin on noradrenaline uptake in vivo was studied both peripherally and centrally. The ability of 6‐hydroxydopamine to lower rat heart noradrenaline levels was found to be very sensitive to inhibition by tricyclic antidepressants. Mianserin was active in this model. However, its ability to block the 6‐hydroxydopamine‐induced fall in rat heart noradrenaline concentration was appreciably less than that of the tricyclics studied.
Mianserin, like tricyclic antidepressants, was essentially devoid of effect on dopamine uptake both in vitro and in vivo.
The ability of mianserin to inhibit [3H]‐5‐hydroxytiyptamine uptake by rat hypothalamic synaptosomes was appreciably less than that of the tricyclic antidepressants studied. Mianserin was essentially devoid of effect on rat brain 5‐hydroxytryptamine uptake in vivo.
It is concluded that in certain situations large doses of mianserin may block noradrenaline uptake in vivo. However, in no way does mianserin rival tricyclic antidepressants in blocking monoamine uptake in vivo. The clinical efficacy of mianserin cannot be attributed to inhibition of monoamine uptake.
PLASMA NORTRIPTYLINE AND CARDIAC RESPONSES IN YOUNG AND OLD RATS
Authors: BONACCORSI AURORA , FRANCO R. , GARATTINI S. , MORSELLI P.L , PITA E. 
Published: July 2012

The relationship between plasma concentrations and cardiac effects of nortriptyline was studied in anaesthetized young and old rats.
Nortriptyline was administered by two consecutive intravenous infusions which resulted in a peak plasma concentration followed by steady state values. Increasing infusion rates were followed by proportional increases in the drug plasma concentrations ranging from 0.15 to 6.0 μg/ml.
In young rats, nortriptyline induced an increase in the heart rate, a right rotation of the electrical axis and a prolongation of the PQ interval. Heart rate changes were not correlated with nortriptyline plasma concentrations, while significant correlations were found for the other two parameters. Plasma concentrations inducing 20% increase of the PQ interval and 40 degrees rotation of the electrical axis were 1.65 and 1.69 μg/ml respectively. Arrhythmias occurred at concentrations higher than 5.2 μg/ml.
Nortriptyline caused more severe cardiac effects in old than in young animals. However, plasma concentrations of nortriptyline in old rats were two to five times higher than those found in young rats at similar infusion rates. A higher concentration of the drug at its sites of action seems to be responsible for the more severe cardiac toxicity of nortriptyline observed in old rats.
INHIBITION BY Cd2+, VERAPAMIL AND PAPAVERINE OF Ca2+‐INDUCED CONTRACTIONS IN ISOLATED CEREBRAL AND PERIPHERAL ARTERIES OF THE DOG
Authors: HAYASHI S. , TODA N. 
Published: July 2012

In helically cut strips of canine cerebral arteries exposed to Ca2+‐free media and depolarized by K+, the addition of Ca2+ caused biphasic (transient and sustained) contractions, while in coronary and mesenteric arteries, the addition of Ca2+ produced a sustained contraction sometimes preceded by a slight transient contraction.
These Ca2+‐induced contractions were attenuated by Cd2+ (5 to 100 μm) in a dose‐dependent manner, the attenuation being greater in cerebral than in coronary and mesenteric arteries. The inhibitory effect of Cd2+ was prevented and partially reversed by 1 mm cysteine.
Verapamil and papaverine were also effective in attenuating the Ca2+‐induced contractions in cerebral and peripheral arteries: susceptibility to verapamil was in the order, cerebral > coronary > mesenteric, while that to papaverine was in the order, cerebral = coronary > mesenteric.
It may be concluded that the agents that interfere with trans‐membrane influxes of Ca2+ cause a greater relaxation in cerebral than in peripheral arteries, as is seen with papaverine, a non‐specific vasodilator.