bluuebunny/crossref_metadata_2025_split huggingface dataset:
RELATIONSHIP BETWEEN LESION FORMATION AND PERMEABILITY OF RAT GASTRIC MUCOSA TO H+ AND OTHER CATIONS
Authors: BUNCE K.T. , McCARTHY J.J. , SPRAGGS C.F. , STABLES R. 
Published: July 2012

The relationship between lesion formation and ionic permeability has been investigated in rat gastric mucosa in vivo. Changes in these parameters were measured in the mucosa treated topically with prostaglandins E2 and A2 and/or aspirin. Particular attention was paid to the net flux of H+ ions across the gastric mucosa.
The effect of aspirin concentrations of 5 mm, 20 mm and ‘40 mm’ (the latter, a suspension in a saturated solution) was investigated. Aspirin concentrations of 20 mm and ‘40 mm’ produced a marked increase in lesion formation and increased the net mucosal to serosal flux of H+ ions. Aspirin 5 mm produced a significant increase in lesion formation but did not cause a significant change in net H+ ion flux. This result suggests that aspirin can have a direct irritant effect on the gastric mucosa and that the back diffusion of H+ ions is not a pre‐requisite for the development of overt mucosal ulceration.
The effect of topically applied prostaglandin E2 (PGE2) on aspirin‐induced gastric mucosal damage was investigated. Concentrations of PGE2 of 10−5m and 10−4m ameliorated aspirin‐induced damage, but these changes were not necessarily accompanied by a significant reduction in net H+ ion flux. Again, this result is not consistent with a direct relationship between lesion formation and mucosal permeability to H+ ions.
Since PGA2 did not ameliorate aspirin‐induced mucosal damage, the protective effect of PGE2 could not be attributed to its conversion to PGA2 in the acidic environment of the gastric lumen.
Changes in gastric mucosal potential difference (p.d.) and net fluxes of Na+ and K+ ions may occur without a concomitant change in the permeability of the gastric mucosa to acid back‐diffusion. Thus, the assumption cannot be made that a change in the permeability of the gastric mucosa to one particular ion reflects a general increase in ionic permeability.
INHIBITION OF TRYPSIN AND PAPAIN BY SODIUM AUROTHIOMALATE MEDIATED BY EXCHANGE REACTIONS
Authors: GRIFFIN M.M. , STEVEN F.S. 
Published: July 2012

Sodium aurothiomalate has been shown to participate in exchange reactions leading to the inhibition of trypsin; for this exchange to take place it was necessary to include in the test system a suitable thiol, such as N‐acetyl‐cysteine.
Neither N‐acetyl‐cysteine nor aurothiomalate on their own had any inhibitory action on trypsin.
The results indicate that aurothiomalate dissociates in the presence of a carrier to form thiosuccinate and gold.
The gold is responsible for trypsin inhibition since independent experiments demonstrated that the total concentration of thiosuccinate was insufficient to cause the observed inhibition of trypsin.
Bovine serum albumin was shown to act as a carrier in place of N‐acetyl‐cysteine.
It is known that histidine in the active centre of trypsin binds heavy metal ions with consequent inhibition of the enzyme. In this study, imidazole was shown to act as a carrier for gold from aurothiomalate to trypsin resulting in inhibition. This inhibition by gold was reversed when higher concentrations of imidazole were added to the test system due to competition for the trypsin‐bound gold by imidazole.
Conversely, the thiol enzyme papain was re‐activated in the presence of low concentrations of sodium aurothiomalate and inhibited by higher concentrations of this reagent in a biphasic manner. This observation will be discussed in relation to the dissociation of sodium aurothiomalate.
These observations can also be explained in terms of exchange reactions involving thiols and free metal ions.
RELATIVE ACTIVITIES OF SUBSTANCE P‐RELATED PEPTIDES IN THE GUINEA‐PIG ILEUM AND RAT PAROTID GLAND, in vitro
Authors: GATER P.R. , JORDAN C.C. , OWEN D.G. 
Published: July 2012

The relative potencies of a series of substance P analogues have been determined for spas‐mogenic activity in the guinea‐pig ileum in vitro and for the release of 86Rb and α‐amylase activity from rat parotid gland slices in vitro. Equipotent molar ratios (EMR), relative to substance P, were determined for all the compounds.
In the rat carotid gland, EC50 values for amylase release were, on average, 35.5 times greater than those for 86Rb release. Analysis of Hill plots suggests that spare receptors exist for 86Rb release but not for amylase release and it is suggested that the stimulus‐response coupling for amylase release may be less efficient than that for 86Rb release.
In the parotid gland, the octapeptide and [<Glu6]‐hexapeptide C‐terminal fragments of substance P were less active than substance P itself, whereas in the ileum, the octapeptide was as active as substance P.
Substitutions at the Phe7 or Phe8 positions in general reduced activity relative to substance P. This effect was particularly apparent in C‐terminal hexapeptide analogues.
Substitutions at the Phe7 and Phe8 positions in C‐terminal hexapeptide analogues produced a greater reduction in activity in the parotid gland than in the ileum. The most marked difference was observed with eledoisin‐related peptide for which the ratio of EMRs for ileum and 86Rb release was 18.1. The unsubstituted C‐terminal octapeptide fragment similarly showed a discrepancy between the two assay systems (EMR ratio, ileum: Rb release = 7.75).
It is suggested that the results may indicate the presence of sub‐populations of ‘substance P receptors’ which are represented at least in different proportions in the two tissues studied, although alternative explanations such as differences in metabolism of agonists are possible.
SELECTIVE POTENTIATION OF NORADRENALINE IN THE GUINEA‐PIG VAS DEFERENS BY 2‐(4‐METHYLAMINOBUTOXY) DIPHENYLMETHANE HYDROCHLORIDE (MCI‐2016), A NEW PSYCHOTROPIC DRUG
Authors: OHIZUMI YASUSHI , TAKAHASHI MASAMI , TOBE AKIHIRO 
Published: July 2012

In the isolated vas deferens of the guinea‐pig, the effects of 2‐(4‐methylaminobutoxy) diphenyl‐methane hydrochloride (MCI‐2016), a new psychotropic drug, on the contractile response to various agonists or transmural electrical stimulation and on the release of noradrenaline (NA) from the tissue were examined and compared with cocaine.
MCI‐2016 (3 × 10−6m) and cocaine (3 × 10−5m) produced a leftward shift (15 and 20 times, respectively) of the dose‐response curves for the contractile effect of NA and increased the maximum contractile response to NA by approximately 7 and 14% respectively.
MCI‐2016 had no apparent effect on the dose‐response curves for methoxamine, acetylcholine and high K, while cocaine markedly shifted those for these agents to the left and increased the maximal responses (10, 16 and 16%, respectively).
MCI‐2016 and cocaine abolished the tyramine (3 × 10−4m)‐induced contraction and inhibited the twitch response to transmural electrical stimulation in a dose‐dependent manner. The inhibitory effects of both drugs on the twitch were reversed by yohimbine (10−5 m).
The spontaneous outflow of NA from the vas deferens was unaffected by MCI‐2016(3 × 10−6m) and cocaine (10−5 m), while the high‐K‐evoked release of NA was increased by both drugs.
In the presence of cocaine (10−5 m), the high‐K‐evoked release of NA was markedly increased by yohimbine (10−5 m) and decreased by clonidine (3 × 10−8m), but only slightly increased by MCI‐2016 (3 × 10−6m).
In phaeochromocytoma cells, both MCI‐2016 and cocaine at concentrations of 10−7 to 10−5 m caused a dose‐dependent inhibition of the [3H]‐NA uptake.
These results suggest that MCI‐2016‐induced supersensitivity is specific for NA and is due to interference with the neuronal uptake process for NA.
MODIFICATION OF ENDORPHIN/ENKEPHALIN ANALGESIA AND STRESS‐INDUCED ANALGESIA BY DIVALENT CATIONS, A CATION CHELATOR AND AN IONOPHORE
Authors: CHAPMAN D.B. , WAY E. LEONG 
Published: July 2012

The possibility that divalent cations may antagonize opiate peptide analgesia and stress‐induced analgesia was examined.
Intracerebroventricular injection of low doses of Ca2+, Mn2+ and Mg2+ antagonized β‐endorphin and methionine‐enkephalin analgesia. Ba2+ and Cd2+ were without effect.
The ionophore, A23187, significantly antagonized β‐endorphin analgesia and the effect was increased when a low dose of Ca2+ was injected at the same time as the ionophore.
Ethylene glycol tetraacetic acid (but not ethylenediamine tetraacetic acid) significantly potentiated endorphin analgesia.
Stress‐induced analgesia, as determined by increased tail‐flick latencies following intraperitoneal injection of acetic acid, was effectively antagonized by naloxone, Ca2+ and Mn2+. The frequency of writhing following acetic acid injection was increased by both naloxone and divalent metal ions, again suggesting antagonism of endogenous opiates.
These results confirm previous findings indicating that divalent metal ions (and especially Ca2+) may be involved in the actions of opiates.
SPECIFIC BUT NONCOMPETITIVE INHIBITION BY 2‐ALKYLTHIO ANALOGUES OF ADENOSINE 5′‐MONOPHOSPHATE AND ADENOSINE 5′‐TRIPHOSPHATE OF HUMAN PLATELET AGGREGATION INDUCED BY ADENOSINE 5′‐DIPHOSPHATE
Authors: CUSACK N.J. , HOURANI S.M.O. 
Published: July 2012

Some 2‐alkylthio derivatives of adenosine 5′‐monophosphate (AMP), adenosine 5′‐monophosphorothioate (AMPS) and adenosine 5′‐triphosphate (ATP) were examined as inhibitors of human platelet aggregation.
2‐Methylthio‐AMP, 2‐ethylthio‐AMP, 2‐(pentan‐l‐yl)thio‐AMP, 2‐ethylthio‐AMPS, 2‐methylthio‐ATP and 2‐ethylthio‐ATP (100 μm) each inhibited aggregation induced by adenosine 5′‐diphosphate (ADP) but not by 11α,9α‐epoxymethano prostaglandin H2, a stable endoperoxide analogue.
Log dose‐response curves to ADP in the absence and presence of each inhibitor were not parallel and the inhibition could not be overcome by high concentrations of ADP.
The ATP analogues achieved greater inhibition of aggregation induced by ADP (5 μm) than did the AMP analogues.
The order of potency of the AMP analogues was 2‐ethylthio‐AMPS > 2‐ethylthio‐AMP > 2‐(pentan‐l‐yl)thio‐AMP > 2‐methylthio‐AMP, and 2‐methylthio‐ATP was more potent than 2‐ethylthio‐ATP.
These 2‐alkylthio substituted analogues of AMP and ATP are specific but noncompetitive inhibitors of ADP‐induced human platelet aggregation.
RATE‐LIMITING STEP IN THE METABOLISM OF POLAR AND NON‐POLAR MONOAMINES IN LUNG AND LIVER
Authors: BEN‐HARARI RUBEN R. , PELEG R. , YOUDIM M.B.H. 
Published: July 2012

Uptake of the non‐hydroxylated amines, [14C]‐tryptamine and [14C]‐benzylamine in rat lung, infused through the pulmonary circulation, was not saturable over the concentration range 2.5–1,000 μm.
The kinetic constants for deamination of a variety of hydroxylated and non‐hydroxylated monoamines in liver, perfused via the portal circulation, with monoamine oxidase activity in homogenates of liver were similar.
In lung, uptake of both [14C]‐tryptamine and [14C]‐benzylamine was inhibited by the monoamine oxidase inhibitor deprenyl and competition occurred between tryptamine, benzylamine and β‐phenylethylamine for uptake.
These results indicate that tryptamine and benzylamine metabolism in lung is not limited by uptake, unlike that of the hydoxylated amines 5‐hydroxytryptamine and noradrenaline and that uptake resembles that of β‐phenylethylamine in lung.
The selectivity of the lung in handling monoamines is not shown by the liver, suggesting that lung has a specific role in clearing certain biogenic monoamines.
THE MECHANISM OF THE POSITIVE INOTROPIC ACTION OF KETAMINE ON ISOLATED ATRIA OF THE RAT
Authors: BARRIGON SANTOS , DE MIGUEL BEATRIZ , TAMARGO JUAN , TEJERINA TERESA 
Published: July 2012

The effect of ketamine (10−7 m‐5 × 10−4 m) on electrical and mechanical properties of isolated atria of the rat was investigated.
On spontaneously beating right atria, ketamine produced a dose‐dependent positive inotropic effect which was accompanied by a progressive reduction in atrial rate.
In electrically driven left atria, ketamine produced a dose‐dependent positive inotropic effect which was accompanied by a parallel increase in df/dtmax and by a prolongation in the time to peak tension and in the time for total contraction. The positive inotropic effect occurred concomitantly with an increase in the height and duration of the plateau phase of the action potential of atrial fibres.
The positive inotropic effect of ketamine varied with the concentration of Ca and Na in the bathing media and the rate of stimulation.
Ketamine decreased post‐extrasystolic potentiation and the amplitude‐interval relationship.
The positive inotropic effect of ketamine was inhibited by verapamil (10−6 m) and by caffeine (4 × 10−3 m).
Ketamine, 5 × 10−5 m and 10−4 m, increased 45Ca uptake in electrically driven left atria. At 10−4 m and 5 × 10−4 m, ketamine also increased 45Ca efflux.
These results suggest that ketamine produces its positive inotropic effect by two possible mechanisms. One of these is presumed to be an effect on the cell membrane which leads to an increased Ca influx into atrial fibres; the other is probably related to the inhibition of Ca sequestration by the sarcoplasmic reticulum.
ALTERATION IN THE LEVEL OF ENDOGENOUS HYPOTHALAMIC PROSTAGLANDINS INDUCED BY Δ9‐TETRAHYDROCANNABINOL IN THE RAT
Authors: COUPAR IAN M. , TAYLOR DAVID A. 
Published: July 2012

Whole brain and regional brain levels of prostaglandin E2 (PGE2)‐like material have been determined following administration of Δ9‐tetrahydrocannabinol (Δ9‐THC) in rats.
Intravenous administration of Δ9‐THC 2 mg/kg, resulted in marked behavioural changes and hypothermia. The behavioural changes consisted mainly of catatonia (most apparent at 30 min after administration of Δ9‐THC), followed by sedation (most evident at 60 min). Hypothermia was marked from 30 min after administration of Δ9‐THC.
Δ9‐THC did not alter the whole brain levels of PGE2‐like material 30, 60 or 120 min after administration.
Δ9‐THC did not alter the levels of PGE2‐like material in the medulla oblongata/pons, midbrain, cortex and cerebellum, 30 min after administration. However, there was a significant reduction of PGE2‐like material in the hypothalamus, 30 min after Δ9‐THC.
It is suggested that the Δ9‐THC‐induced decrease in hypothalamic PGE2‐like material may contribute to the hypothermia observed following Δ9‐THC administration.
PROTECTIVE EFFECTS OF THE GLUCOCORTICOID, BUDESONIDE, ON LUNG ANAPHYLAXIS IN ACTIVELY SENSITIZED GUINEA‐PIGS: INHIBITION OF IgE — BUT NOT OF IgG — MEDIATED ANAPHYLAXIS
Authors: ANDERSSON P. , BRATTSAND R. 
Published: July 2012

The effect of glucocorticoid pretreatment on antigen‐induced bronchoconstriction was studied in guinea‐pigs actively sensitized to two different ovalbumin regimens (one producing IgE‐ and IgG‐like antibodies and the other exclusively IgG‐like antibodies).
Budesonide (50 mg/kg) and hydrocortisone (50 mg/kg) given as one intraperitoneal injection 15–20 h before the anaphylactic test or as two consecutive intraperitoneal injections 5 and 6 days before, led to a decreased bronchial capacity. In this respect glucocorticoid pretreatment was effective only in guinea‐pigs sensitized to produce both IgE‐like and IgG‐like antibodies.
Budesonide pretreatment also reduced the capacity of anaphylactically‐challenged chopped lung tissue to release histamine in guinea‐pigs sensitized to produce both IgE‐ and IgG‐like antibodies.
Budesonide pretreatment did not change the levels of circulating IgG1a and IgE‐like homocytotropic antibodies as measured by passive cutaneous anaphylaxis; nor did it affect histamine or methacholine‐induced bronchoconstriction in vivo or the capacity of histamine or methacholine to contract the guinea‐pig isolated trachea preparation or the isoprenaline‐induced relaxation of this preparation.
The selective inhibitory effects of budesonide and hydrocortisone on IgE‐mediated but not IgG‐mediated anaphylaxis and the relevance to human atopic disease are discussed.
ULCERATIVE COLITIS: EFFECT OF SULPHASALAZINE, ITS METABOLITES AND INDOMETHACIN ON THE ABILITY OF HUMAN COLONIC MUCOSA TO METABOLIZE PROSTAGLANDINS in vitro
Authors: HILLIER KEITH , MASON P.J. , PACHECO S. , SMITH C.L. 
Published: July 2012

Homogenates of mucosa from human colon metabolize [3H]‐prostaglandin E1 in the presence of nicotinamide adenine dinucleotide to 15‐oxo prostaglandin E1 or 15‐oxo, 13,14 dihydro prostaglandin E1.
Metabolic capacity of tissue from patients with active ulcerative colitis under treatment with sulphasalazine (0.021 ± 0.004 nmol/mg protein ± s.e. mean) did not differ from mucosa of normal patients (0.02 ± 0.004 nmol/mg protein) during 1 h incubation.
Sulphasalazine inhibits prostaglandin E1 metabolism by mucosal homogenates in a dose‐dependent manner with an ID50 of 125 μm. Its therapeutically active metabolite, 5‐aminosalicylic acid (2.6 mm) was without significant inhibitory activity.
Indomethacin inhibits prostaglandin E1 metabolism by colonic mucosa with an ID50 of 388 μm.
At present we cannot clearly relate the therapeutic benefit of sulphasalazine and its therapeutically active metabolite, 5‐aminosalicylic acid, in ulcerative colitis to their effects on prostaglandin E synthesis or metabolism in vitro.
RELATION OF PLASMA RENIN ACTIVITY TO THE ANTIHYPERTENSIVE EFFECT OF MK 421 IN THE RAT
Authors: BRADSHAW DAVID , FRANZ PETER H. , SUGDEN A. LOUISE 
Published: July 2012

The effect of the angiotensin converting enzyme inhibitor, MK 421 (N‐((S)‐1‐(ethoxycarbonyl)‐3‐phenylpropyl)‐l‐Ala‐l‐Pro), on the blood pressure of two‐kidney Goldblatt hypertensive rats has been investigated in relation to the initial plasma renin activity (PRA) and the initial blood pressure of the individual animals.
Blood pressure was monitored by an indirect tail‐cuff method at 1, 3, 6 and 24 h after dosing. MK 421 produced a fall in blood pressure in the majority of animals, but the extent of this reduction varied considerably between individuals.
The change in blood pressure showed a significant correlation with both the initial PRA and the initial blood pressures of the animals. However, only a modest correlation was found between the initial PRA and the degree of hypertension.
MK 421 (10 mg/kg, orally) produced a mean blood pressure change which was statistically significant (P< 0.001) at all times tested.
It is concluded that the degree of antihypertensive activity of MK 421 is related to the degree of activity of the renin‐angiotensin system which, in this model at least, is reflected by the PRA.
PHARMACOLOGICAL RESPONSES OF HUMAN AND PORCINE LUNG PARENCHYMA, BRONCHUS AND PULMONARY ARTERY
Authors: GOLDIE ROY G. , PATERSON JAMES W. , WALE JANET L. 
Published: July 2012

Responses of preparations of human and porcine isolated bronchus and pulmonary artery to carbachol (CCh), methacholine, histamine, 5‐hydroxytryptamine (5‐HT), (−)‐noradrenaline (NA), (−)adrenaline (Adr) and (±)‐isoprenaline (Iso) were compared with responses to the same agonists in isolated lung parenchyma strips.
All preparations from both human and porcine lung contracted in response to histamine and all, except preparations of porcine pulmonary artery, contracted in response to CCh. Human and porcine pulmonary artery and parenchyma strip contracted in response to NA while bronchial preparations invariably relaxed. Iso caused relaxation of human and porcine bronchus and parenchyma strip. Although 5‐HT was completely inactive in tissues isolated from pig lung, this amine was a powerful spasmogen in human pulmonary artery, relaxed human bronchus and caused variable responses in human parenchyma.
Results indicate that the pharmacological characteristics of human and porcine parenchyma strips may be explained in terms of responses of vascular or airways smooth muscle.
THE EFFECT OF ANAESTHETIC AGENTS ON CEREBRAL CORTICAL RESPONSES IN THE RAT
Authors: ANGEL A. , GRATTON DENISE A. 
Published: July 2012

In rats, surgically anaesthetized with Urethane, an increase in the depth of anaesthesia upon administration of ethyl carbamate (Urethane), pentobarbitone sodium (Nembutal), thiopentone sodium (Intraval), althesin, ketamine, trichloroethylene, halothane, methoxyflurane, diethyl ether, ethyl‐vinyl ether, cyclopropane, enflurane or chloroform resulted in a dose‐dependent increase in the latency, and decrease in the amplitudes of the initial positive and negative components of the short latency cortical response to electrical stimuli applied to the forepaw.
The same changes were seen when starting from initially unanaesthetized rats and anaesthetizing them with Urethane.
With all the inhalational agents used these changes lasted for as long as the administration except with nitrous oxide where the changes in the cortical response were transient.
The tranquillizing agents diazepam, chlordiazepoxide, and haloperidol showed no such action. Chloral hydrate and chlorpromazine, on the other hand, produced moderate changes in the evoked cortical response similar to those seen with the other anaesthetic agents used.
THE EFFECT OF CIMETIDINE ON BASAL GASTRIC ACID SECRETION IN THE RAT
Authors: BROUGHTON N.S. , MORRIS J.F. 
Published: July 2012

The effect of cimetidine on the basal gastric acid secretion of the rat has been investigated in an anaesthetized lumen‐perfused preparation.
Six rats previously given large doses of cimetidine orally showed no significant difference in basal gastric acid secretion when compared with six control rats.
Intravenous administration of 1 mg and 8 mg of cimetidine failed to inhibit significantly basal gastric acid secretion.
Although rats with a basal gastric acid secretion above 2.5 μEq/10 min showed a consistent small reduction in basal gastric acid secretion after intravenous cimetidine, this was not seen in rats with a basal gastric acid secretion below 2.5 μEq/10 min.
These results contrast sharply with the pronounced inhibition of basal gastric acid secretion by cimetidine in man and the possible reasons for this are discussed.
The results are also contrasted with previous work on gastric fistula rats which showed higher basal gastric acid secretion and significant inhibition by cimetidine.
ROLE OF ADRENAL MEDULLA IN MORPHINE‐INDUCED HYPERTHERMIA THROUGH CENTRAL ACTION
Authors: WALLENSTEIN MARTIN C. 
Published: July 2012

The role of the adrenal glands, in morphine‐induced hyperthermia was studied in normal, chemically‐sympathectomized, adrenalectomized, adrenal‐demedullated or splanchnicotomized rats.
In restrained female rats, 5 mg/kg morphine produced hyperthermia whereas 20 mg/kg and 40 mg/kg produced hypothermia.
After adrenalectomy, 5 mg/kg morphine did not produce hyperthermia.
After adrenal‐demedullation or adrenal‐denervation (splanchnicotomy), 5 mg/kg morphine did not produce hyperthermia.
The results suggest that, in the rat, the adrenal medulla plays an important role in morphine‐induced hyperthemia, and that morphine acts centrally to stimulate the medulla.