bluuebunny/crossref_metadata_2025_split huggingface dataset:
METABOLITES OF ARACHIDONIC ACID FORMED BY HUMAN GASTROINTESTINAL TISSUES AND THEIR ACTIONS ON THE MUSCLE LAYERS
Authors: BENNETT A. , HENSBY C.N. , SANGER G.J. , STAMFORD I.F. 
Published: July 2012

Gas chromatography‐mass spectrometry demonstrated the presence of arachidonic acid (AA), 6‐keto‐prostaglandin F1α and thromboxane B2 (TxB2) in all extracts of homogenized muscle or mucosa from human stomach, terminal ileum or sigmoid colon. Prostaglandin D2 (PGD2), PGE2 or PGF2α were usually found more often in the mucosal extracts. The 12‐hydroxy‐derivative of AA (12‐HETE) was detected in all extracts of the colon but in only some of the other tissues
Most prostanoids tested contracted the longitudinal muscle, the order of potency being U‐46619 (an epoxymethano analogue of PGH2)>PGE2>PGF2α>PGD2; PGI2 usually caused relaxation, whereas its breakdown products or TxB2 had weak and variable effects
U‐46619 or, less potently, PGF2α contracted the circular muscle, whereas PGI2 and usually PGE2 caused relaxation. PGD2, 6‐keto‐PGF1α, 6, 15‐diketo‐PGF1α or TxB2 usually had little or no effect
PGI2 antagonized contractions to some excitatory prostanoids, without greatly affecting contractions to acetylcholine
For both muscle layers there was a gradient in sensitivity to prostanoids along the gastrointestinal tract. The sensitivities were stomach>distal ileum>sigmoid colon
The results are discussed in relation to gastrointestinal physiology and pathophysiology.
TWO TYPES OF γ‐AMINOBUTYRIC ACID RECEPTOR ON EMBRYONIC SENSORY NEURONES
Authors: DUNLAP KATHLEEN 
Published: July 2012

Embryonic sensory neurones of the chick grown in dissociated cell culture respond to application of low concentrations of γ‐aminobutyric acid (GABA) with a change in resting membrane resistance (Rin) and/or a change in action potential duration (APD) (Dunlap & Fischbach, 1978; Choi & Fischbach, 1981). Intracellular microelectrode recording techniques were employed to determine if these two effects are mediated by the same, or different, GABA receptors.
Cells responded, for the most part, with a change in either Rin or APD, but 10% of the cells exhibited both effects. In the latter cells the two responses were clearly distinguishable as discussed below.
The proportion of neurones exhibiting a GABA‐induced decrease in Rin declined during the first week in vitro while the proportion exhibiting a decrease in APD increased during that time.
The two effects were pharmacologically distinct. Muscimol, a GABA analogue, produced only the change in Rin (ED50 = 5.5 μm) while baclofen, another analogue of GABA, produced only the change in APD (ED50 = 1 μm). The analogues were approximately equipotent with GABA. Bicuculline, a GABA antagonist, blocked the muscimol‐induced change in Rin (but not the baclofen‐induced change in APD) in a dose‐dependent fashion with an ID50 = 0.7 μm.
The time courses of the two effects were different. The change in APD resulting from a brief application of GABA (or baclofen) was prolonged relative to the rapid return to control associated with the GABA‐ (or muscimol‐) induced change in Rin.
Desensitization of the two responses exhibited separate time courses. In the continual presence of the agonists, GABA‐ and muscimol‐induced decreases in Rin completely desensitized in ca. 10 s while GABA‐ and baclofen‐induced decreases in APD persisted undiminished throughout a prolonged (1 min) application of the drugs and returned to control only after cessation of application.
It is concluded that embryonic chick sensory neurones in culture exhibit two types of GABA receptor that differ in their functional and pharmacological properties. Implications of these results are discussed.
ACUTE EFFECTS OF PROPRANOLOL ON THE CIRCULATION AND ON OXYGEN UPTAKE IN CONSCIOUS RATS
Authors: LEDINGHAM JOHN M. , LEES DOUGLAS C.P. 
Published: July 2012

The acute effect of orally administered propranolol (100 mg/kg) on blood pressure, heart rate, cardiac output, venous pressure, haemoglobin concentration and oxygen uptake was studied in conscious rats.
Oxygen uptake was measured in a closed circuit respirometer and cardiac output determined by the direct Fick method. Other variables were measured by means of chronically implanted cannulae.
Significant falls occurred in heart rate (8.9%), cardiac output (30.5%), derived stroke volume (21.3%) and oxygen uptake (12.2%).
There were significant rises in arterial blood pressure (12.9%), derived arterial resistance (69%), arterio‐venous oxygen difference (31.5%) and arterial haemoglobin concentration (6.3%).
A rise in venous pressure occurred in lightly anaesthetized rats but was only of borderline significance.
Correlations between the different variables revealed only one significant relationship, between heart rate and oxygen uptake.
It is concluded that only one primary site of action of propranolol has to be postulated to account for these findings, that of the well known negative inotropic and chronotropic effect on the heart.
THE CALCIUM ANTAGONISTIC EFFECTS OF CYPROHEPTADINE ON CONTRACTION, MEMBRANE ELECTRICAL EVENTS AND CALCIUM INFLUX IN THE GUINEA‐PIG TAENIA COLI
Authors: LOWE1 D.A. , MATTHEWS E.K. , RICHARDSON B.P. 
Published: July 2012

The ability of cyproheptadine (Cph) to inhibit membrane translocation of calcium in smooth muscle was investigated by studying the drug's action on contraction, electrical activity and calcium influx in the guinea‐pig taenia coli.
Cph>10−6M reduced the amplitude of normal spontaneous contractions and concurrently decreased the number of action potentials occurring with each slow‐wave of depolarization (sucrose‐gap recordings). These inhibitory effects of Cph were antagonized by increasing the medium [Ca] three fold to 7.68 mM.
Intracellular recordings showed that Cph>2 × 10−6M decreased the amplitude and extended the duration of the action potential. These effects were only partially reversible in normal medium whereas large overshooting action potentials were again seen in 7.68 mM Ca medium.
High frequency mechanical activity was produced by inclusion of veratridine 5 × 10−6M in the perfusate. Low concentrations of Cph (> 10−7m) reduced the amplitude of such contractions at a faster rate than they did normal spontaneous contractions.
At concentrations between 10−7 and 10−6M, Cph fully reduced the tonic component of contractions elicited in 112 mM isotonic KC1 whilst having little or no effect on either (i) the initial phasic KC1 contraction or (ii) the ‘repolarization contracture’ normally produced on wash‐out of the KC1 or (iii) the spontaneous contractions before and after KC1 treatment. In contrast, at Cph 2 × 10−6M, the repolarization contracture, as well as the isotonic KC1 contraction, was totally blocked whereas spontaneous contractions were still unaffected. Progressively higher Cph concentrations inhibited all components of this contractile cycle.
Dose‐response curves for the rate of drug‐induced relaxation of tonic contractures produced in hypertonic 42.7 mM high‐potassium medium, showed the calcium antagonistic potency of Cph to be intermediate between that of chlorpromazine and D600. The minimum Cph concentration for effect lay between 1 and 5 × 10−7M, and the effects of Cph 2 × 10−6M (approximately the ID50) were totally antagonized by 12.8 mM Ca.
By means of a lanthanum wash procedure, Cph>2 × 10−6M was found to decrease the 45Ca uptake occurring into strips of taenia coli in normal medium, although the maximum effect (at Cph 10−5m) amounted to only 25 % inhibition of the uptake occurring into control strips (also found with D600). The increased uptake occurring in hypertonic 44.7 mM high‐potassium medium was inhibited in a dose‐dependent manner by Cph 1 × 10−7M.
The results are consistent with an action of Cph in reducing the flow of Ca2+ through voltage‐dependent Ca channels in the smooth muscle cell membrane. It is suggested that the interaction of Cph molecules with such sites is dependent upon membrane potential as well as drug concentration.
CONTRACTILE EFFECT OF MORPHINE AND RELATED OPIOID ALKALOIDS, β‐ENDORPHIN AND METHIONINE ENKEPHALIN ON THE ISOLATED COLON FROM LONG EVANS RATS
Authors: HUIDOBRO‐TORO J. PABLO , WAY E. LEONG 
Published: July 2012

Morphine and related synthetic surrogates as well as β‐endorphin and methionine enkephalin caused a contractile response of the longitudinal musculature of the terminal colon of Long Evans rats.
The muscular contraction caused by the narcotic analgesics exhibited stereospecificity, with levorphanol being about 50 times more potent than dextrorphan and (−)‐methadone 4 times more potent than (+)‐methadone. In addition, the rank order in potency of a homologous series of N‐alkyl substituted norketobemidones demonstrated that the activity of these compounds in eliciting contractile responses corresponded to that for analgesic efficacy in the rat and also correlated to the ability of these derivatives to inhibit the muscular twitch evoked by electrical stimulation of the guinea‐pig ileum.
Naloxone blocked the contractile response of the opiates following competitive kinetics; the naloxone pA2 values for morphine, etorphine, levorphanol and methadone were very close, in spite of the marked differences in potency of these agents.
The contractile effect of morphine on the rat colon was abolished by incubation of the tissues with tetrodotoxin 2.0 × 10−7 M or by decreasing the external Ca2+ level 100 fold. Increasing the external Ca2+ concentration caused an apparent non‐competitive antagonism of the response to morphine.
Pretreatment of the tissues with hexamethonium 8.3 × 10−5 M caused a modest antagonism of the morphine effect while atropine 5.8 × 10−7M did not significantly modify the morphine contractile effect. In contrast, methysergide 10−5 M caused a 10 fold increase in the morphine EC50.
Colons from rats rendered tolerant‐dependent on morphine were markedly less sensitive to the contractile effects of morphine than those from placebo‐treated controls. Tolerance to morphine was also accompanied by an increased sensitivity to the contractile effects of 5‐hydroxytryptamine (5‐HT).
A marked increase in the spontaneous muscular activity of segments of the terminal colon of rats chronically treated with morphine was found to occur upon removal of the residual morphine in the tissues by repetitive washings. The spontaneous activity was arrested by applications of morphine, suggesting that physical dependence can be demonstrated in vitro in this particular preparation.
It is concluded that the opiate‐induced contractile response is mediated via stereospecific, naloxone‐sensitive, opiate receptors and that the muscular response involves the activation of a 5‐HT neurone in the nerve terminals of the colon.
ENTERAL ADMINISTRATION OF INSULIN IN THE RAT
Authors: BAR‐ON H. , BERRY E.M. , ELDOR A. , KIDRON M. , LICHTENBERG D. , ZIV E. 
Published: July 2012

The effect of the surfactant, Cetomacrogol 1000, on the absorption of insulin across the rectal mucosa has been studied.
Rectal administration of microenemata containing Cetomacrogal 1000 and insulin causes a rise in the plasma concentration of insulin and a consequent fall in the blood glucose concentration in diabetic and non‐diabetic rats.
The hypoglycaemic response is dependent on both the concentration of surfactant and the dose of insulin administered.
The results suggest that the transport of insulin across the rectal mucosa is facilitated by Cetomacrogal 1000.
THE EFFECT OF CIMETIDINE ON BASAL AND STIMULATED PEPSIN SECRETION IN THE ISOLATED WHOLE STOMACH OF THE RAT
Authors: BUNCE K.T. , GREWAL M. , PARSONS M.E. 
Published: July 2012

The isolated stomach preparation of the immature rat has been used to study the stimulation and inhibition of pepsin secretion.
The isolated stomach secretes a basal level of pepsin. High concentrations (10−3m) of the H2‐receptor antagonist, cimetidine, and the muscarinic receptor blocking drug, atropine, did not affect this secretion in a manner which was consistently of statistical significance.
Concentrations of histamine of 10−5M, 10−4M and 10−3M stimulated maximum levels of pepsin output of 126%, 155% and 299% respectively of control. There was no evidence that this secretion was secondary to the stimulation of acid secretion.
Cimetidine (10−4m and 10−3m) produced a dose‐related inhibition of the pepsin output to 10−3M histamine, suggesting that histamine H2‐receptors mediate this response.
Atropine (10−3m) had no effect on the pepsin response to 10−3M histamine, suggesting that muscarinic mechanisms play no part, even modulatory, in this secretion.
TYRAMINE ANTAGONISTIC PROPERTIES OF AGN 1135, AN IRREVERSIBLE INHIBITOR OF MONOAMINE OXIDASE TYPE B
Authors: FINBERG J.P.M. , TENNE M. , YOUDIM M.B.H. 
Published: July 2012

The effects of the irreversible monoamine oxidase (MAO) inhibitors, AGN 1133, AGN 1135 and (−)‐deprenyl, on tyramine and noradrenaline responses and uptake of [3H]‐metaraminol were investigated in the isolated vas deferens of the rat. Uptake of [3H]‐metaraminol and [3H]‐octopamine was compared in mouse vas deferens. The modification of tyramine and noradrenaline‐induced pressor responses by AGN 1133 and AGN 1135 was examined in anaesthetized rats and cats.
AGN 1133 (7.5 × 10−6m) greatly potentiated responses to tyramine in the rat isolated vas deferens. Both AGN 1135 and (−)‐deprenyl inhibited tyramine responses selectively at concentrations above 10−3m (which caused almost complete inhibition of MAO types A and B) but tyramine responses were potentiated on washing out the inhibitors.
AGN 1135 (10−4m) and (−)‐deprenyl (10−5m) inhibited [−3H]‐metaraminol uptake by about20% in rat and mouse vas deferens; neither inhibitor affected [−3H]‐octopamine uptake in mouse vas deferens. Desmethylimipramine (10−6m) inhibited amine uptake by more than 70%.
AGN 1133 (1.5 mg/kg) potentiated pressor responses to tyramine in rats and cats whereas AGN 1135 (1.5 mg/kg) did not.
AGN 1135 possesses tyramine antagonistic activity which is qualitatively similar to that of (−)‐deprenyl but which cannot satisfactorily be explained by inhibition of neuronal or granular amine uptake.
PROSTAGLANDINS, THROMBOXANES AND THE PREGNANT RAT UTERUS AT TERM
Authors: PHILLIPS1 CHRISTINE A. , POYSER N.L. 
Published: July 2012

Prostaglandin and thromboxane release from the term pregnant (Day 22) rat uterus in vitro has been measured by radioimmunoassay and gas chromatography combined with mass spectrometry.
Prostacyclin (prostaglandin I2, PGI2) and thromboxane A2 (TXA2) (measured as their metabolites, 6‐oxo‐PGF1α and TXB2. respectively) were released in large amounts, while PGE2 and PGF2α were released in smaller amounts. PGD2 was released in the largest quantities.
Treatment of the term pregnant rat uterus in vitro with the PGI2 synthesis inhibitors, 15‐hydroperoxy arachidonic acid (15‐OOH AA) and tranylcypromine caused spasm of the tissue.
15‐OOH AA caused dose‐dependent increases in prostaglandin release, while tranylcypromine caused a fall in the release of PGE2 but did not affect the release of other prostaglandins. A possible reason for the effect of 15‐OOH AA on prostaglandin release is discussed.
Indomethacin prevented spontaneous activity of the term pregnant rat uterus in vitro. Contractions were restored by prostaglandins and their order of potency was PGE2>PGF2α>PGI2>PGD2>>6‐oxo‐PGFlα = TXB2
EFFECTS OF HISTAMINE ON THE RESTING AND STIMULATION‐INDUCED RELEASE OF [3H]‐NORADRENALINE IN GUINEA‐PIG ISOLATED ATRIA
Authors: RAND M.J. , STORY D.F. , WONG‐DUSTING H.K. 
Published: July 2012

The sympathetic transmitter stores of guinea‐pig isolated atria were labelled with [3H]‐noradrenaline. The effects of histamine (0.3 to 100 μmol/l) on resting and stimulation‐induced (S‐I, 2 Hz for 10 s) release of radioactivity were investigated.
Histamine, in low concentrations (0.3 and 1 μmol/l) had no effect on resting release but inhibited S‐I release of radioactivity. The inhibition was abolished by the H2‐receptor antagonist, cimetidine (10 μmol/l) and also by the H1‐receptor antagonist, mepyramine (1μmol/l).
The inhibitory actions of histamine on S‐I release were not due to indirect effects involving α‐adrenoceptors, β‐adrenoceptors, muscarinic cholinoceptors or prostaglandin synthesis.
Histamine in a high concentration (100 μmol/l) increased the resting and S‐I release of radioactivity. The increase in resting release was abolished by the neuronal uptake blocking drug cocaine (30 μmol/l) but the increase in S‐I release was only partially blocked by cocaine.
EFFECTS OF ASPIRIN, PREDNISOLONE AND INDOMETHACIN ON NEPHROTOXIC SERUM NEPHRITIS IN THE RAT
Authors: KUROKAWA HIROSHI , SAKAMOTO KIMIKO 
Published: July 2012

The effects of aspirin, prednisolone, and indomethacin on nephrotoxic serum nephritis in rats was studied. The nephritis was induced by a single intravenous injection of nephrotoxic serum (NTS, rabbit anti‐serum against the water‐soluble renal antigen of the rat). The injection of NTS induced the heterologous phase of proteinuria (within a day after NTS injection) and then the autologous phase (5 to 7 days after NTS injection). The effect of drugs given before the NTS (i.e. prophylactically) or after the NTS (i.e. therapeutically) was investigated.
Aspirin, which was given orally at doses of 150 and 250 mg/kg daily from the day before NTS injection, suppressed the‐development of proteinuria in both the heterologous and the autologous phase, and lowered the serum cholesterol level towards the normal level. Aspirin (250 mg/kg daily, orally) had no significant effect against the established proteinuria in the autologous phase.
Prednisolone, which was given orally at doses of 3 and 5 mg/kg daily from the day before NTS injection, elevated the proteinuria in the heterologous phase, while inhibiting the development of proteinuria in the autologous phase. Prednisolone (5 mg/kg daily, orally) was ineffective against established proteinuria in the autologous phase.
Indomethacin (3 mg/kg daily, orally) did not exert any significant effect on proteinuria in either the heterologous or the autologous phase.
BLOOD ALCOHOL LEVELS IN RATS: NON‐UNIFORM YIELDS FROM INTRAPERITONEAL DOSES BASED ON BODY WEIGHT
Authors: BLOOM FLOYD , LAD PUSHKARAJ , PITTMAN QUENTIN , ROGERS JOSEPH 
Published: July 2012

Sprague‐Dawley rats (n = 72) weighing from 125 to 450 g were injected intraperitoneally (i.p.) with 16% (w/v) ethanol to provide 1, 2, or 3 g/kg doses.
Resulting blood alcohol levels (BALs) demonstrated a general inadequacy of dose/body weight (g/kg) formulations of ethanol to provide uniform BALs in animals of different weights.
BAL differences between heavier and lighter rats were not well accounted for by developmental changes in liver weight or alcohol dehydrogenase activity.
From the data, a table was derived of more appropriate ethanol injection volumes to produce 0–300 mg% BALs (20 mg% increments) in rats from 100–500 g (10 g increments).
EFFECTS OF PHENCYCLIDINE AND ITS DERIVATIVES ON ENTERIC NEURONES
Authors: GINTZLER ALAN R. , ZUKIN R. SUZANNE , ZUKIN STEPHEN R. 
Published: July 2012

The effects of N‐(1‐phenylcyclohexyl) piperidine (PCP) and related drugs on isolated intact segments of the guinea‐pig ileum were determined.
1–1‐(2‐Thienyl) cyclohexylpiperidine (TCP), PCP and ketamine decreased the height of electrically induced contractions (0.1 Hz) of intact segments of isolated guinea‐pig ileum.
Thirty to forty percent of the inhibition of contraction height (0.1 Hz) was reversed by pretreatment with the pure narcotic antagonist, naloxone. This naloxone‐reversible component showed cross‐tolerance with morphine.
PCP pretreatment caused a shift to the right in the dose‐response curve to acetylcholine (ACh) that was not parallel with the control dose‐response curve. Thus PCP does not interact with the muscarinic cholinoceptor in a strictly atropine‐like competitive fashion.
Binding sites for [3H]‐PCP were detected in homogenates of the guinea‐pig longitudinal muscle‐myenteric plexus preparation.
The affinity constants and the rank order of potencies of various PCP derivatives competing with [3H]‐PCP for binding suggest that these binding sites are very similar to those found in the central nervous system.
These data suggest that the guinea‐pig isolated ileum may be used as an in vitro system for studying the mechanism of action of phencyclidines.
CORONARY VASOCONSTRICTOR AND VASODILATOR ACTIONS OF ARACHIDONIC ACID IN THE ISOLATED PERFUSED HEART OF THE RAT
Authors: BELO SUSAN E. , TALESNIK JAIME 
Published: July 2012

The administration of arachidonic acid (AA) to the isolated perfused heart of the rat usually produced biphasic coronary responses characterized by initial vasoconstriction followed by prolonged vasodilatation. However, some responses were predominantly vasoconstrictor or vasodilator.
The non‐steroidal anti‐inflammatory agents (NSAA) indomethacin (1–5 mg/l) and naproxen (12.5–25 mg/l) reversibly inhibited both phases of the response induced by AA.
Pretreatment of animals with indomethacin (5 mg/kg) or naproxen (25 mg/kg) daily, resulted in unaltered coronary response to AA. Subsequent addition of NSAA to the perfusate produced inhibition of the AA effect.
Short infusions of acetylsalicylic acid at low concentrations (2.9 μg/ml), dipyridamole (0.6 μg/ml) and sulphinpyrazone (28.7 μg/ml) selectively inhibited the vasoconstrictor phase of the response to AA.
It was confirmed that metabolic coronary dilatation induced by cardiostimulation was inhibited by prolonged A A administration; this effect was prevented by NSAA pretreatment. Reactive hyperaemic responses to short lasting occlusions of coronary inflow were unaffected by NSAA.
Linolenic, linoleic, dihomo‐γ‐linolenic and oleic acid usually produced decreases in coronary flow which were unaffected by NSAA, dipyridamole or sulphinpyrazone.
Intra‐aortic injections of AA, prostacyclin (PGI2) and prostaglandin E2 (PGE2) in the intact rat produced a dose‐dependent decrease in blood pressure with the AA response inhibited by indomethacin. PGI2 and PGE2 produced long lasting coronary vasodilatation in the isolated heart.
The coronary actions of AA appear to be due to its transformation, within the easily accessible vascular wall, into prostaglandin and thromboxane‐like substances. We suggest that a vasoconstrictor thromboxane A2‐like substance may be responsible for coronary vasospasm.
Coronary insufficiency may also result from an inhibition of compensatory metabolic coronary dilatation by increased synthesis of PGE2 within the myocardial cell.
EFFECTS OF 5‐HYDROXYTRYPTAMINE ON CANINE ISOLATED CORONARY ARTERIES
Authors: PORQUET MARIE‐FRANCE , POURRIAS BERNARD , SANTAMARIA RAPHAEL 
Published: July 2012

The effects of 5‐hydroxytryptamine (5‐HT) were studied in vitro on proximal and distal portions of canine interventricular and circumflex coronary arterial strips. 5‐HT produced concentration‐related contractions in the proximal portion whether contracted previously with KCl or not. These responses were still present after either chemical sympathetic denervation or release of noradrenaline induced by K+‐free salt solution. In contrast, the distal portions of coronary arteries did not respond to 5‐HT.
Concentration‐response curves to 5‐HT exhibited a classical hyperbolic shape with a calculated Hill‐coefficient of approximately 1.
Methysergide and phentolamine but not morphine shifted to the right and depressed the maximum of the dose‐response curves to 5‐HT.
It is concluded that the contractions produced by 5‐HT in the proximal portion of the interventricular and circumflex coronary arteries are not due to the release of endogenous noradrenaline. The vessels appear to possess separate receptors for 5‐HT and noradrenaline and the 5‐HT responses belong to neither the M nor the D type.