bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of atropine and secoverine on gastric secretion and motility in the mouse isolated stomach
Authors: Davison J.S. , Greenwood Beverley , Najafi‐Farashah A. , Read N.W. 
Published: July 2012

The isolated perfused stomach of the mouse was used to study the effect of atropine and secoverine on bethanechol‐induced gastric acid secretion and gastric motility.
Both atropine and secoverine inhibited cholinergically induced gastric acid secretion and gastric motility.
Inhibition of gastric acid secretion by atropine and secoverine occurred at a similar dose‐range (10−9 and 2 × 10−9m).
Secoverine inhibited bethanechol‐induced hypermotility at doses (10−11 m and above) that were lower than those of atropine (2 × 10−9 m and above) required to produce this effect.
Secoverine, unlike atropine markedly inhibited gastric motility at lower doses than those which affected secretion.
Dynorphin‐related peptides cause motor dysfunction in the rat through a non‐opiate action
Authors: Faden Alan I. , Jacobs Thomas P. 
Published: July 2012

We compared effects on motor function of four peptides belonging to the dynorphin family ‐dynorphin‐(1–17) (DYN‐(1–17)), dynorphin‐(1–13) (DYN‐(1–13)), dynorphin‐(1–8) (DYN‐(1–8)) and α‐neo‐endorphin (αNE).
After intrathecal administration, each of these peptides produced dose‐related, flaccid, hindlimb paralysis, with the order of potency being DYN‐(1–17) > DYN‐(1–13) > αNE ≏DYN‐(1–8).
This motor dysfunction was not reversed or blocked by the opiate receptor antagonist naloxone and was not produced by a variety of other κ‐selective agonists.
However, paralysis was produced by des‐Tyr‐dynorphin (DYN‐(2–17)), which does not act at the opioid receptor.
Taken together, the present studies show that dynorphin‐related peptides, uniquely amongst opioids, produce motor dysfunction, an action which does not appear to be mediated by opioid receptors.
A 1H n.m.r. study of the role of the glutamate moiety in the binding of methotrexate to Lactobacillus casei dihydrofolate reductase
Authors: Antonjuk David J. , Birdsall Berry , Cheung H.T. Andrew , Clore G. Marius , Feeney James , Gronenborn Angela , Roberts Gordon C.K. , Tran Trung Q. 
Published: July 2012

The binding of a series of amide derivatives of methotrexate to Lactobacillus casei dihydrofolate reductase has been studied by inhibition constant measurements and by 1H n.m.r. spectroscopy.
Amide modification of the α‐carboxylate of methotrexate was found to prevent interaction of the γ‐carboxylate with the imidazole of His 28.
Estimates of the contributions to the binding energy from the α‐carboxylate‐Arg 57 and γ‐carboxylate‐His 28 interactions have been made from a combination of inhibition and n.m.r. data.
Actions of picrotoxinin and related compounds on the frog spinal cord: the role of a hydroxyl‐group at the 6‐position in antagonizing the actions of amino acids and presynaptic inhibition
Authors: Kudo Yoshihisa , Niwa Haruki , Tanaka Atsuko , Yamada Kiyoyuki 
Published: July 2012

The frog spinal cord has been used to test the effects of naturally occurring picrotoxane compounds (picrotoxinin, picrotin, tutin and coriamyrtin) and semisynthetic ones (6‐acetylpicrotoxinin and anhydropicrotin) on the electrical activities of dorsal and ventral roots and on amino acid‐induced depolarizations of primary afferent terminals.
Picrotoxinin, tutin and coriamyrtin (10−5‐3 × 10−5m), which have a free hydroxyl group at the 6‐position, caused a gradual depolarization in both ventral and dorsal roots. The depolarizations were accompanied by a reduction in the size of the dorsal root potential (DR‐DRP), dorsal root reflex (DR‐DRR) and ventral root potential (DR‐VRP) and by an augmentation of the first spike potential and polysynaptic components in the ventral root reflex (DR‐VRR).
6‐Acetylpicrotoxinin (10−5‐3 × 10−5m) caused a slight hyperpolarization in both roots, and this hyperpolarization was accompanied by the augmentation of DR‐DRP, DR‐VRP and DR‐VRR. The DR‐DRR was reduced or abolished by the compound.
Picrotoxinin, tutin and coriamyrtin reduced γ‐aminobutyric acid (GABA)‐, β‐alanine‐ and taurine‐induced depolarizations of primary afferent terminals. 6‐Acetylpicrotoxinin showed almost the same degree of inhibition of β‐alanine and taurine as did picrotoxinin, but the GABA‐antagonizing action of the compound was significantly weaker than was that of picrotoxinin.
Picrotoxinin, tutin, coriamyrtin and 6‐acetylpicrotoxinin all blocked presynaptic inhibition of the first spike potential caused by antidromic conditioning stimulation.
The present results suggest that the hydroxyl group at the 6‐position of picrotoxane compounds are important for antagonism of the effects of GABA, but not of β‐alanine and taurine and for the blocking action of the presynaptic inhibition in the frog spinal cord.
Presynaptic α‐adrenoceptors: do exogenous and neuronally released noradrenaline act at different sites?
Authors: Baker D.J. , Drew G.M. , Hilditch A. 
Published: July 2012

The effects of dopamine receptor and α‐adrenoceptor agonists and antagonists on the stimulation‐evoked overflow of radioactivity from strips of dog saphenous vein previously loaded with [3H]‐noradrenaline have been examined alone and in combination.
In the presence of neuronal and extraneuronal catecholamine uptake inhibitors, noradrenaline (0.1–1 × 10−6 m) and dopamine (0.01–1 × 10−6 m) both inhibited the stimulation‐evoked overflow of radioactivity. Sulpiride (1 × 10−6 m) was without effect and prazosin (1 × 10−7 m) had little effect on stimulation‐evoked overflow but yohimbine enhanced it approximately 2 fold; the effect of yohimbine was similar at concentrations of 1 × 10−7 and 1 × 10−6 m.
Sulpiride abolished the inhibitory effect of dopamine on stimulation‐evoked overflow, but was without effect against noradrenaline. When allowance was made for the effects of yohimbine, alone, on overflow, yohimbine (1 × 10−7 m) had no effect against dopamine and minimal effects against noradrenaline. A similar result was obtained when the concentration of yohimbine was increased to 1 × 10−6 m. Prazosin did not antagonize the effect of noradrenaline.
In the absence of the uptake inhibitors, clonidine (0.01–1 × 10−5 m) inhibited stimulation‐evoked overflow of radioactivity. Yohimbine (1 × 10−6 m) was without effect on its own and antagonized the effects of clonidine at a concentration of 0.1 × 10−5 m, but not at 0.01 or 1.0 × 10−5 m.
These findings suggest that dopamine inhibits overflow by stimulating presynaptic dopamine receptors on the terminals of the noradrenergic nerves supplying the dog saphenous vein. The interaction between yohimbine and noradrenaline is discussed in terms of the current concepts of control of transmitter release mediated via presynaptic α2‐adrenoceptors.
Effects of α‐ and β‐adrenoceptor blockade on the neurally evoked overflow of endogenous noradrenaline from the rat isolated heart
Authors: Dart A.M. , Dietz R. , Hieronymus K. , Kübler W. , Mayer E. , Schömig A. , Strasser R. 
Published: July 2012

β‐Adrenoceptor blockade by propranol (4 × 10−6 m) was without effect on the overflow of endogenous noradrenaline from the isolated heart of the rat induced by stimulation of sympathetic nerves for 1 min at 1 and at 4Hz. The increase in heart rate in response to such stimulation was abolished by propranolol treatment.
α2‐Adrenoceptor blockade by yohimbine (10−6m) induced approximately a two fold increase in the overflow of endogenous noradrenaline induced by stimulation of sympathetic nerves for 1 min at 1 and at 4 Hz.
A combination of yohimbine (10−6m) and desipramine (10−7 m) induced a more than 3 fold increase in the overflow of endogenous noradrenaline produced by sympathetic nerve stimulation at 1 and at 4 Hz. Heart rate increases produced by such stimulation were intensified.
These results provide no evidence for the feedback stimulation of presynaptic β‐adrenoceptors in this preparation. The action of α2‐blockade was equipotent at stimulation frequencies of 1 and 4 Hz.
Release of noradrenaline and dopamine by nerve stimulation in the guinea‐pig and rat vas deferens
Authors: Bell C. , Gillespie J.S. , Macrae I.M. 
Published: July 2012

Spontaneous and nerve stimulated release of noradrenaline and dopamine from rat and guinea‐pig vas deferens have been measured electrochemically after separation by high performance liquid chromatography (h.p.l.c).
In the absence of nerve stimulation both noradrenaline (NA) and dopamine were released into the bathing fluid in the rat but in the guinea‐pig only noradrenaline could be detected. Drugs which block neuronal and extraneuronal uptake of catecholamines had little effect on spontaneous overflow but both tetraethylammonium and phenoxybenzamine increased overflow.
Transmural nerve stimulation (5–10 Hz) increased catecholamine overflow in both species and dopamine release was now measurable from the guinea‐pig vas. In the rat, the proportion of dopamine to NA was unchanged from that released spontaneously. The release of both amines was little affected by drugs that block neuronal and extraneuronal uptake and a monoamine oxidase inhibitor, but was inhibited by tetrodotoxin 0.2 μg ml−1.
In the guinea‐pig tetraethylammonium 10 mm doubled overflow and phenoxybenzamine 10−5 m increased it by five times but the dopamine percentage remained constant and equal to the control.
Following nerve stimulation the amount of dopamine released expressed as a percentage of total catecholamine release was 6% for the rat and 1.3% for the guinea‐pig. These values were considerably higher than the comparable figures for dopamine: NA content of the two tissues (2% and 0.5% respectively). Repeated periods of stimulation depleted these tissue stores and the depletion of dopamine was significantly greater than that of NA.
Our interpretation of these results is that both dopamine and NA are released from a common store during normal noradrenergic transmission. While all or most of the axonal dopamine is contained in this releasable pool, most of the axonal NA lies in a second, less readily released pool.
Interactions of Cholinesterase inhibitors and glucocorticoids with ketamine and pentobarbitone‐induced general anaesthesia in the rat: possible effects on central cholinergic activity
Authors: Leeuwin Remy S. , van der Wal Jan K. , Spanjer Willem 
Published: July 2012

Doses of 100, 150 and 200 μg kg−1 of the Cholinesterase inhibitor neostigmine reverse the anaesthetic action of ketamine. The antagonistic effect is increased as the dose is increased. The duration of anaesthesia induced by pentobarbitone is reversed by the Cholinesterase inhibitor in doses of 150, 200 and 250 μg kg−1.
Choline, in a dose of 50 mg kg−1, significantly antagonizes the action of the two anaesthetics, whereas hemicholinium‐3, an inhibitor of the uptake of choline and the synthesis of acetylcholine, markedly potentiates their action.
Dexamethasone induces a significant reduction of the duration of anaesthesia produced by ketamine and pentobarbitone. The potentiation of the anaesthetic effect caused by hemicholinium‐3 is also reversed by dexamethasone.
The acetylcholine content in rat cerebral cortex is increased after treatment with ketamine and pentobarbitone.
Measurements of the course of the plasma level of pentobarbitone do not reveal alterations in the pharmacokinetic profile by either neostigmine or dexamethasone.
These results indicate that central cholinergic systems may somehow be involved in the anaesthesia induced by ketamine and pentobarbitone and that the interactions described in this paper may be the result of modification by neostigmine and dexamethasone of the alterations in cholinergic activity caused by the two anaesthetics.
Frusemide releases renin in the rat kidney when prostacyclin synthesis is suppressed
Authors: Barden Anne E. , Mahoney Denis P. , Tunney Anne M. , Vandongen Robert 
Published: July 2012

The effect of inhibiting prostaglandin (PG) synthesis on basal and frusemide‐stimulated renin secretion was examined in the rat isolated perfused kidney. The stable PGI2 derivative, 6‐keto PGF1α, was measured by radioimmunoassay in urine collected from the kidney.
Treatment of rats with indomethacin (3.0 mg kg−1) reduced 6‐keto PGF1α excretion from 121.3 ± 39.1(n = 9) to 15.5 ± 6.6 (n = 9) pg min−1 (P < 0.02) but had no effect on basal renin secretion. Renal perfusion pressure, flow rate and vascular resistance were similar in treated and control rats. Mean urine flow was lower after treatment.
Infusion of frusemide (250 μg min−1) did not alter 6‐keto PGF1α excretion in control or indomethacin‐treated (P > 0.05) rats. Although renin secretion was increased during frusemide infusion, there was no significant difference between control (1,806 ± 384 ng angiotensin I (AI) min−1) and treated (2,310 ± 554 ng AI min−1) rats (P > 0.05). Propranolol, at a dose (8 pig min−1) which suppressed renin secretion after isoprenaline stimulation, had no effect on the response to frusemide in indomethacin‐treated rats.
These results demonstrate that frusemide‐stimulated renin secretion in the rat kidney does not require intact renal PGI2 synthesis and is independent of β‐adrenergic mechanisms.
Converting enzyme inhibition in the rat by captopril is accompanied by potentiation of carrageenin‐induced inflammation
Authors: Boura A.L. A. , Svolmanis A.P. 
Published: July 2012

Hind paw oedema in rats, measured by plethysmography or extravasation of Evans Blue dye into the skin, after subplantar injection of submaximal doses of carrageenin (1–100 μg) was significantly increased for 4 h during kininase II inhibition with captopril (1 mg kg−1, s.c.).
Submaximal oedema, as assessed by paw swelling, after subplantar bradykinin (0.1–1.0 μg) was also significantly increased after subcutaneous administration of this dose of captopril, whereas that in response to either histamine (2–20 μg) or prostaglandin E2 (2 μg) was unchanged.
The pain threshold of the paw, injected with carrageenin (1 μg) was lowered significantly after subcutaneous administration of captopril (1 mg kg−1).
Potentiation by captopril (1 mg kg−1, s.c.) of paw swelling in response to intraplantar carrageenin (100 μg) or bradykinin (1 μg) was reduced by prior subcutaneous administration of indomethacin (5 mg kg−1).
It is suggested that normally, tissue kininase II activity is sufficient to decrease the inflammatory response of the hind paw to carrageenin or bradykinin. After inhibition of kininase II with captopril, bradykinin levels are increased and interact with concomitantly released prostaglandins to potentiate inflammation.
Alterations to the electrical activity of atrial muscle isolated from the rat heart, produced by exposure in vitro to amiodarone
Authors: Northover B.J. 
Published: July 2012

Glass microelectrodes were used to record transmembrane electrical activity from cells located just beneath the endocardial surface of the left atrial free wall of rat hearts during superfusion and electrical stimulation in vitro at 37°C.
Availability of the fast sodium channel for current flow was inferred from the maximum rate of rise of membrane potential during phase O of the action potential (V̇max).
Muscle exposed to polysorbate 80 (10 to 80 μg ml−1) showed a concentration‐dependent lengthening of action potential duration (APD) but no detectable change in V̇max.
Amiodarone (1 to 20 μg ml−1) was dissolved in physiological salt solution with the aid of polysorbate 80 (50 μg ml−1) and caused a concentration‐dependent prolongation of APD and a decrease in V̇max, both of which were slow to develop and extremely slow to wash‐out. The speed of onset of action of amiodarone varied with drug concentration and ranged from a few minutes with high concentrations to many hours with low concentrations.
Some effects of nicotine on food and water intake in undeprived rats
Authors: Clarke P.B.S. , Kumar R. 
Published: July 2012

Undeprived rats were tested in their home cages for intake of water and powdered food, starting 15 min after subcutaneous (s.c.) injection of (−)−nicotine bitartrate or 0.9% w/v NaCl solution (saline). In the first 2 h, nicotine (0–0.4 mg kg−1 base) markedly reduced water intake in a dose‐related way, leaving food intake unchanged. Food and water intake up to 24 h after injection was unaffected.
Rats (n = 6 per group) were then injected daily with nicotine (0.4 mg kg−1 base, s.c.) or saline for one month. Intermittent tests with saline (in place of nicotine) during this period did not reveal any signs of abstinence. A dose‐response study similar to the first was then carried out, and little or no tolerance was found to the hypodipsic action of nicotine. Nicotine also reduced food intake, irrespective of chronic treatment. Subsequently, daily injections were discontinued, and spontaneous intake did not differ in rats previously maintained on nicotine, relative to control animals.
Mecamylamine (0.3, 1.5 mg kg−1, s.c.) prevented nicotine‐induced hypodipsia, whereas chlorisondamine (0.02, 0.1 mg kg−1 s.c.) was ineffective. Both ganglion blockers reduced food intake.
Nicotine did not reduce drinking in rats preloaded with a hypertonic saline solution.
It is suggested that nicotine reduces water intake in undeprived rats, probably by acting centrally. Since this action changes little with repeated testing, it may provide a useful index of one or more central actions of the drug.
Substance P can contract the longitudinal muscle of the guinea‐pig small intestine by releasing intracellular calcium
Authors: Holzer P. , Lippe Irmgard Th. 
Published: July 2012

The contraction of the longitudinal muscle of the guinea‐pig isolated ileum in response to substance P (SP) in high [K+] medium and in Ca2+‐free solution which contained EGTA has been investigated in order to examine whether excitation‐contraction coupling involves the release of Ca2+ from an intracellular store.
In tissues contracted by K+, high concentrations of SP (> 0.1 μM) were still capable of causing a slight, transient contraction.
Bathing the ileum in a Ca2+‐free medium for 2.5 min greatly diminished the potency and efficacy of SP in contracting the longitudinal muscle but concentrations of 2.2–22 μM SP were still able to produce a response 30–40% of maximal.
The responsiveness to SP was completely lost within 10 min of bathing in Ca2+‐free medium but was partially restored by a brief exposure (0.5–2 min) to high concentrations of Ca2+ (9–72 mM). The restorative effect of Ca2+ depended on the concentration of Ca2+ and on the time for which the tissue was exposed to this Ca2+ concentration.
The fact that high concentrations of SP were able to elicit a contraction in media containing high [K+] or no Ca2+, suggested that they may do so by releasing Ca2+ from an intracellular store which is not as sensitive to removal of extracellular Ca2+ or as easily accessible to EGTA as the extracellular space of the muscle. The location of this store is not known; it may be associated with the internal side of the cell membrane.
There is apparently an overlap between the Ca2+ pool associated with the action of SP and the Ca2+ pools utilized by acetylcholine, histamine or tetraethylammonium, which accounts for the cross‐desensitization observed between these agonists. It was not possible to determine whether autodesensitization to SP also results from depletion of an intracellular Ca2+ store.
The dependence of excitatory junction potential amplitude on the external calcium concentration in mouse vas deferens during narcotic withdrawal
Authors: Einstein R. , Lavidis N. A. 
Published: July 2012

The dependence of neurotransmitter release on calcium was evaluated in adrenergic terminals from mice that were acutely withdrawn from chronic morphine treatment (CMT).
A two fold increase in the number of writhes in response to an i.p. injection of acetylcholine was induced in mice by CMT and subsequent withdrawal.
A shift to the left in the relationship between the excitatory junction potential (e.j.p.) amplitude and extracellular calcium concentration ([Ca]o) was induced in vasa deferentia from CMT‐withdrawn mice.
A reduction in the degree of facilitation of transmitter release during a short low‐frequency train of impulses and an increase in the amount of transmitter release during a high‐frequency train of impulses was induced in vasa deferentia from CMT‐withdrawn mice.
The adaptive mechanism of the terminals to the sustained presence of morphine may involve an increase in the probability that the release sites will release transmitter either via increase in calcium influx or an increase in the affinity of calcium to the hypothetical X‐receptor.
Energy conservation by nisoldipine in ischaemic heart
Authors: De Jong Jan W. , Huizer Tom , Tijssen Jan G.P. 
Published: July 2012

We studied the effect of the calcium entry blocker nisoldipine on ATP catabolism in the rat heart, perfused according to Langendorff. Even 1 nM nisoldipine induced vasodilatation; concentrations of 30 nM and higher caused significant negative inotropy.
The drug had a very strong affinity for silicon rubber tubing.
Myocardial ischaemia was induced by lowering the perfusion pressure, which reduced flow without nisoldipine by 85%. The efflux of purine nucleosides and oxypurines rose 14 fold. Nisoldipine reduced this efflux of ATP catabolites dose‐dependently. The highest concentration, 300 nM, suppressed ischaemic purine production completely.
The action of the drug was antagonized by an increase in Ca2+‐concentration in the perfusion fluid.
We also showed the protective effect of nisoldipine on adenine nucleotides in freeze‐clamped hearts. A concentration of 20 nM partially prevented the reduction of ATP and adenylate energy charge due to ischaemia.
We conclude that relatively low doses of nisoldipine effectively prevent ATP breakdown in ischaemic rat heart.
Effect of exposure to radiation on the inflammatory process and its influence by diclofenac
Authors: El‐Ghazaly M. , Kenawy S. , Khayyal M.T. , Roushdy H. , Saleh S. 
Published: July 2012

The effect of radiation exposure on the inflammatory process was studied in rats using the carrageenan‐induced paw oedema and adjuvant‐induced arthritis tests.
Irradiation (0.5,1 and 2 Grays) resulted in a significant augmentation of the tissue response to carrageenan and the early phase of adjuvant‐induced arthritis, but suppressed the late phase.
Diclofenac (1–5 mg kg−1) effectively reduced the exaggerated inflammatory response in irradiated animals in both the carrageenan paw oedema and adjuvant‐induced arthritis tests. The drug also had a prophylactic value in guarding against the induction of radiation damage.
The inflammatory responses produced by irradiation and the benefits obtained by drug treatment may be related to changes in tissue prostaglandin levels and/or changes in the immune system.