bluuebunny/crossref_metadata_2025_split huggingface dataset:
POTENTIATION BY SUBSTANCE P OF CONTRACTIONS OF THE ISOLATED VAS DEFERENS OF THE MOUSE ELICITED BY ELECTRIC FIELD STIMULATION AND BY DRUGS
Authors: BLACKWELL M. , JAMES T.A. , STARR M.S. 
Published: July 2012

Isolated vasa deferentia from the mouse were opened longitudinally and suspended in Krebs solution at 37°C in an organ bath. Contractions of the muscle were elicited by electric field stimulation, noradrenaline (10−6m) and acetylcholine (10−6m). Continued transmural stimulation evoked a biphasic response comprising a rapid twitch followed about 10s later by a smaller, sustained rise in muscle tone.
The amplitudes of nerve‐mediated and drug‐induced responses were considerably potentiated by substance P (SP) in the dose range 10−12 to 10−7m. Higher concentrations of SP were directly spasmogenic. The sensitizing property of SP was dose‐dependent and was usually well maintained, but always disappeared quickly on washing the preparation. In some experiments SP facilitated the twitch, but not the subsequent phase of the electrically‐induced contraction or the response to externally applied noradrenaline.
Phentolamine (10−6m) failed to block this effect of SP, but itself potentiated the nerve‐mediated twitch, and completely abolished the sustained secondary contraction.
Desmethylimipramine (10−6m) enhanced the delayed contraction but not the immediate contraction.
The uptake of tritiated noradrenaline (3 × 10−7m) by vasa was inhibited by desmethylimipramine (10−6m) and increased by nialamide (3 × 10−5m), but was not modified by SP (10−6m).
Nerve‐mediated release of accumulated radioactivity was accelerated by phentolamine, but not by SP or desmethylimipramine.
These findings suggest that SP sensitizes the muscle cells to depolarizing stimuli but that it has no facilitatory effect on sympathetic neural elements.
A COMPARISON OF NICOTINE AND STRUCTURALLY RELATED COMPOUNDS AS DISCRIMINATIVE STIMULI
Authors: CHANCE WILLIAM T. , KALLMAN MARY D. , ROSECRANS JOHN A. , SPENCER R. MASON 
Published: July 2012

Of seven nicotine‐like compounds tested as discriminative stimuli in the rat, only 3‐pyridyl‐meth‐ylpyrollidine (3‐PMP) generalized to the stimulus effects of nicotine.
3‐PMP caused equivalent nicotine‐like responding at a dose (800 μg/kg) approximately 4 times that used for the original nicotine discrimination (200 μg/kg). The ED50 for 3‐PMP was about 5 times that for nicotine.
Testing of the compounds as possible antagonists of the nicotine‐elicited cue were negative.
The nicotine‐like cue produced by an 800 μg/kg injection of 3‐PMP was effectively blocked by mecamylamine but not by hexamethonium or atropine. Thus, 3‐PMP appears to produce generalization to the nicotine cue via action on central nicotinic‐cholinoceptors as has been previously reported for the nicotine discriminative stimulus.
Mecamylamine blocked the stimulus‐effects of 3‐PMP (800 μg/kg) and of nicotine (200 μg/kg) with an ED50 of 0.32 and 0.20 mg/kg respectively.
COMPARISON OF THE RESPONSES OF SINGLE CORTICAL NEURONES TO TYRAMINE AND NORADRENALINE: EFFECTS OF DESIPRAMINE
Authors: BEVAN P. , PUN R.Y.K. , SZABADI E. 
Published: July 2012

The technique of microelectrophoresis was used in order to compare the actions of tyramine and noradrenaline on single neurones in the cerebral cortex of the rat.
Tyramine could both excite and depress cortical neurones. Each tyramine‐sensitive cell was also sensitive to noradrenaline. There was a high correlation between the directions of responses to tyramine and noradrenaline, most cells excited by tyramine being excited by noradrenaline, and most cells depressed by tyramine being depressed by noradrenaline.
In the case of both excitatory and depressant responses, tyramine appeared to be less potent than noradrenaline.
Tyramine evoked ‘slower’ responses than noradrenaline, both the latencies to onset and the recovery times being longer for responses to tyramine than for responses to noradrenaline.
When the rates of release of tyramine and noradrenaline from micropipettes were measured in vitro, no significant difference could be observed between the transport numbers of the two drugs. Thus the difference in potency between the two drugs, and the difference in the time courses of responses to the two drugs, are presumably of biological origin.
Desipramine could discriminate between neuronal responses to tyramine and noradrenaline: responses to tyramine were antagonized, while responses to noradrenaline were either potentiated or unaffected. Responses to DL‐homocysteic acid were not affected by desipramine.
The results are consistent with the hypothesis that tyramine is an indirectly acting sympathomimetic amine in the brain, and desipramine acts by blocking the uptake of both tyramine and noradrenaline into presynaptic noradrenergic nerve terminals.
THE EFFECTS OF UPTAKE, ON α‐ADRENOCEPTOR ANTAGONIST POTENCY IN DOG SAPHENOUS VEIN
Authors: HUMPHREY P. P. A. 
Published: July 2012

The effects of α‐adrenoceptor antagonists on contractile responses to noradrenaline and methoxamine were examined in isolated saphenous vein strips of the dog.
Phentolamine, labetalol and thymoxamine antagonized responses to methoxamine to a greater extent than responses to noradrenaline.
Cocaine (3.0 × 10−5 mol/1) increased the potency of noradrenaline by about eight fold, but had little or no effect on the potency of methoxamine.
In the presence of cocaine (3.0 × 10−5 mol/1) the potency of the antagonists against noradrenaline was increased such that the pA2 values were then similar to those obtained against methoxamine.
It is concluded that the lower potency of phentolamine, labetalol and thymoxamine as antagonists of noradrenaline than of methoxamine is due to the presence of an avid saturable uptake! process in the saphenous vein.
A COMPARISON OF THE ANTIFERTILITY EFFECTS OF ALKYLATING AGENTS AND VINCA ALKALOIDS IN MALE RATS
Authors: COOKE R.A. , NIKLES A. , ROESER H.P. 
Published: July 2012

The anti‐fertility effects of cyclophosphamide, nitrogen mustard, vincristine and vinblastine were studied and compared in male rats.
The effects of the drugs on body weight and haematological values were used to monitor the pharmacological actions of the drugs.
All four drugs impaired fertility, the severity of the impairment depending on dose and duration of treatment.
Testicular size and histological appearances remained mostly normal, even in infertile animals, but seminiferous tubules were fewer in number and maturation arrest at the spermatid level was evident in some sections.
Recovery of drug‐induced infertility occurred in 64% of treated animals, 9 to 40 weeks after cessation of treatment.
Morbidity and mortality were much higher with alkylating agents than with vinca alkaloids for approximately similar degrees of impairment in fertility.
THE EFFECT OF STIMULUS INTENSITY ON α‐ADRENOCEPTOR‐MEDIATED FEED‐BACK CONTROL OF NORADRENALINE RELEASE
Authors: HARPER BARBARA , HUGHES I. E. 
Published: July 2012

Mouse vas deferens stimulated transmurally (2.5 Hz, 2–32 V, 40–620 mA, for 45 s) responded with a twitch and a secondary contraction. Both responses were abolished by cinchocaine and were voltage‐dependent.
In tissues previously incubated with [3H]‐(—)‐noradrenaline, stimulation also produced an increase in tritium overflow from the tissue. Phentolamine increased tritium overflow by 19% at high stimulus intensities (30 V, 600 mA) and by 130% at low stimulus intensities (11 V, 200 mA).
It is concluded that α‐adrenoceptor‐mediated feed‐back control of noradrenaline release is more marked at low stimulus intensities and that this is compatible with a role for calcium ions in this control mechanism.
AN INVESTIGATION OF THE ROLE OF GANGLIA IN THE INNERVATION OF THE RAT ANOCOCCYGEUS MUSCLE: AN ELECTRICAL AND MECHANICAL STUDY
Authors: McKIRDY H.C. , MUIR T.C. 
Published: July 2012

A preparation is described which allows the rat anococcygeus muscle to be stimulated via its two extrinsic nerves. Each nerve contains both excitatory and inhibitory fibres. A ganglionated nerve plexus lies on the surface of the muscle.
The possibility that at least part of the excitatory pathway was interrupted by a ganglion synapse lying in one of the nodes of plexus close to the muscle was suggested by the observations that (a) the excitatory response to extrinsic nerve stimulation was reduced by the nicotinic antagonists tubocurarine (0.13 to 0.26 mm) and dihydro β‐erythroidine (0.1 to 0.14 mm), (b) Fibres from one extrinsic nerve were shown to synapse on a ganglion cell from which intracellular recordings were made while the output from this ganglion cell was traced microscopically to the muscle.
Intracellular recording from ganglion cells in this plexus indicated that cholinergic synaptic transmission occurred in these ganglia. Tubocurarine (0.13 mm) and hexamethonium (1.3 mm) reversibly abolished intracellularly‐recorded synaptic potentials.
Hexamethonium (0.1 to 1 mm) initially enhanced the motor response to nerve stimulation and raised muscle tone, probably by an action involving pre‐ and postsynaptic sites. Subsequently, hexamethonium inhibited the response to extrinsic nerve stimulation presumably by an effect at ganglia lying along the excitatory pathway. Hexamethonium enhanced, without subsequently inhibiting, the response to exogenously added noradrenaline in both untreated and 6‐hydroxydopamine‐treated rats. These results suggest that the initial enhancement produced by hexamethonium involved sites at postganglionic nerve endings and on smooth muscle receptors.
Inhibitory responses were obtained following extrinsic nerve stimulation when the tone of the muscle was raised and the excitatory response abolished by either guanethidine (3 μm) alone or by carbachol (10 μm) followed by phentolamine (3 μm). The inhibitory response was not reduced by hexamethonium (up to 2.8 mm) tubocurarine (up to 1.3 mm) or by atropine (up to 1 μm).
β‐ADRENOCEPTOR ANTAGONISTS INHIBIT THE BEHAVIOURAL RESPONSES OF RATS TO INCREASED BRAIN 5‐HYDROXYTRYPTAMINE
Authors: COSTAIN D.W. , GREEN A.R. 
Published: July 2012

The effect of various β‐adrenoceptor blocking agents on the 5‐hydroxytryptamine (5‐HT)‐induced hyperactivity response produced in rats by administration of tranylcypromine (10 mg/kg i.p.) followed by L‐tryptophan (50 mg/kg i.p.) has been investigated.
(±)‐Alprenolol, (±)‐timolol, (+)‐sotalol, (±)‐pindolol (all at 40 mg/kg) all inhibited the hyperactivity response to some degree when given 45 min before the tranylcypromine, as did (±)‐oxprenolol when given after the L‐tryptophan.
β‐Adrenoceptor antagonists that are not found in the brain in appreciable amount after peripheral injection, (+)‐atenolol, (±)‐practolol, (+)‐labetalol and (+)‐acebutalol, did not inhibit the 5‐HT‐mediated behaviour.
Neither the β‐selective drug (±)‐metoprolol, nor the β2‐selective drug (±)‐butoxamine inhibited the behavioural response.
The drugs that blocked the 5‐HT‐mediated behaviour did not alter brain 5‐HT concentrations, synthesis rate or the accumulation of 5‐HT following tranylcypromine/L‐tryptophan. However, they did inhibit the hyperactivity produced by the suggested 5‐HT agonist, 5‐methoxy N,N‐dimethyltrypt‐amine, indicating that the β‐adrenoceptor blocking drugs were inhibiting the post‐synaptic 5‐HT‐mediated response.
Circling produced by methamphetamine (3 mg/kg) in unilateral nigro‐striatal lesioned rats was not altered by alprenolol, sotalol, pindolol or metaprolol, indicating that these drugs do not alter dopamine‐mediated behaviour.
It is concluded that non‐selective (fix and p2) adrenoceptor antagonists which have a high brain/ blood ratio following their peripheral injection, block 5‐HT‐mediated behavioural responses in the rat.
THE RELEASE OF PROSTAGLANDINS AND THROMBOXANES FROM GUINEA‐PIG LUNG BY SLOW REACTING SUBSTANCE OF ANAPHYLAXIS, AND ITS INHIBITION
Authors: ENGINEER DINAZ M. , MORRIS H.R. , PIPER PRISCILLA J. , SIROIS P. 
Published: July 2012

Rabbit aorta contracting substance (RCS; consisting mainly of thromboxane A2) and prostaglandin‐like material were released from guinea‐pig isolated perfused lungs by injection of slow reacting substance of anaphylaxis (SRS‐A).
SRS‐A was resistant to boiling and proteolytic enzymes and was therefore distinguished from rabbit aorta contracting substance releasing factor (RCS‐RF).
The release of RCS and prostaglandin‐like material by SRS‐A was anatagonized by indomethacin (1 μg/ml), betamethasone and dexamethasone (4 to 50 μg/ml).
Imidazole (200 μg/ml) inhibited the formation of thromboxane A2 but not that of prostaglandins.
The activity of SRS‐A on guinea‐pig ileum and its ability to release RCS and prostaglandins were destroyed by incubation with arylsulphatase (0.83 μg to 1 mg/ml) and with lipoxidase (16.5 to 50 μg/ml): SRS‐A lost activity on incubation with bovine serum albumin (9 μg/ml) due to protein binding.
LOCALIZATION OF VASODILATOR DOPAMINE RECEPTORS IN THE CANINE HINDLIMB
Authors: BELL C. , STUBBS A. 
Published: July 2012

Vascular responses to local injection of dopamine and isoprenaline have been compared in the blood‐perfused gracilis muscle and hind paw pads of dogs anaesthetized with chloralose.
In the paw pads, dopamine (0.5 to 5.0 ug) caused a transient vasoconstriction followed by dose‐dependent vasodilatation. α‐Adrenoceptor blockade converted this response to pure vasodilatation, which was attenuated or abolished by the dopamine‐receptor antagonist, haloperidol (1 to 2mg i.a.). In the gracilis, dopamine produced only vasoconstriction. Following α‐adrenoceptor blockade this was abolished, but only a very small dilator response was revealed.
Isoprenaline (0.05 to 0.5 ug) caused dose‐dependent dilatation in both beds, which was attenuated by propranolol (0.1 mg/kg i.v.).
Glyceryl trinitrate (0.2 to 5.0 ug) was used to assess vascular reactivity. When responses to isoprenaline and dopamine were compared with those to glyceryl trinitrate, both beds had approximately equal reactivity to isoprenaline. In contrast the paw pads were 10 fold more responsive to dopamine than was the gracilis.
We conclude that the vessels of the paw pads play an important part in the femoral dilator response to dopamine.
COMPARATIVE PHARMACOLOGICAL AND HISTOCHEMICAL EVIDENCE FOR PURINERGIC INHIBITORY INNERVATION OF THE PORTAL VEIN OF THE RABBIT, BUT NOT GUINEA‐PIG
Authors: BURNSTOCK GEOFFREY , CROWE RAHIMA , WONG HELEN K. 
Published: July 2012

Intramural nerve stimulation elicited a powerful relaxation of the longitudinal muscle of the rabbit portal vein in the presence of atropine and guanethidine, but not of the guinea‐pig portal vein.
Intramural nerve stimulation of the rabbit portal vein produced a 13 fold increase in release of 3H‐adenyl compounds after preloading with [3H]‐adenosine. About 50% of this release was abolished by guanethidine. All release was abolished by tetrodotoxin. No significant release of radioactive compounds was observed during intramural nerve stimulation of the guinea‐pig portal vein in the presence of guanethidine, although there was a 6 fold increase in release of radioactivity in the absence of drugs.
Histochemical studies using quinacrine, which binds ATP showed a fine fluorescent nerve plexus, nerve bundles, and ganglion cells in the rabbit portal vein, but not in the guinea‐pig portal vein. This plexus was still present after chemical sympathectomy with 6‐hydroxydopamine.
Adenosine 5′‐triphosphate (ATP) relaxed the rabbit portal vein, but usually produced a biphasic response, consisting of a contraction followed by a relaxation, of the guinea‐pig portal vein.
Prostaglandins E1 and E2 caused contraction of the rabbit portal vein. Indomethacin, a prostaglandin synthesis inhibitor, potentiated the relaxations of the rabbit portal vein produced by both non‐adrenergic, non‐cholinergic nerve stimulation and ATP.
High concentrations of antazoline and phentolamine, which antagonize purinergic responses in the guinea‐pig taenia coli, caused a loss of basal tone so that it was not possible to assess their effects on the responses of the portal vein to either non‐adrenergic, non‐cholinergic nerve stimulation, or ATP.
Comparison of the results on the portal vein of the rabbit and guinea‐pig provides support for the view that: (i) quinacrine fluorescence can be used to localize purinergic nerves and that the rabbit portal vein is supplied by these nerves; (ii) ATP is released from adrenergic nerve fibres, although, based on histochemical analysis, about 3 to 7 times less than is released from purinergic nerve fibres.
SATURABLE ADENOSINE 5′‐TRIPHOSPHATE‐INDEPENDENT BINDING OF [3H]‐OUABAIN TO BRAIN AND CARDIAC TISSUE in vitro
Authors: AKERA TAI , BRODY THEODORE M. , WIEST SALLY A. 
Published: July 2012

Several investigators have proposed that membrane Na+, K+‐adenosine 5′‐triphosphatase (Na+, K+‐ATPase) is a mechanism for the transmembrane transport of cardiac glycosides, rather than the receptor for pharmacological actions of these agents. This implies that the glycosides bind to an intracellular constituent (receptor) other than Na+, K+‐ATPase.
In search for such a receptor site, saturable ATP‐independent [3H]‐ouabain binding was studied in rat brain and dog and guinea‐pig heart homogenates. The binding of the glucoside to this site results in a relatively unstable complex which is stabilized by K+ to a lesser extent than is the complex formed with the ATP‐dependent binding to Na+, K+‐ATPase.
The ATP‐independent ouabain binding sites are more abundant in rat brain tissue than in cardiac tissue, and have a lower ouabain affinity compared to the binding sites on Na+, K+‐ATPase.
These results do not support the contention that there are intracellular inotropic receptors for digitalis.
PRESYNAPTIC AND POSTSYNAPTIC CONTRIBUTIONS TO ONTOGENY OF SYMPATHETIC CONTROL OF HEART RATE IN THE PRE‐WEANLING RAT
Authors: SEIDLER F.J. , SLOTKIN T.A. 
Published: July 2012

The dependence of heart rate on sympathetic nerve development and on ontogeny of cardiac responses to sympathetic neurotransmitters was evaluated in neonatal rats by use of the ganglionic blocking agent, chlorisondamine, and the β‐adrenoceptor agonist, isoprenaline.
Basal heart rates of anaesthetized 4, 7 and 11 day old rats were the same as in adult rats, but the heart rate in 16 day old rats (an age at which sympathetic tone appears to be elevated) was significantly higher.
Chlorisondamine failed to lower heart rate significantly in 4 or 7 day old rats, but lowered the rate by 50 to 80 beats per min in the older animals and eliminated the difference in rate between 16 day old and the other ages; atropine had little or no effect on heart rate.
Heart rate responses to isoprenaline were lower in 4, 7 and 11 day old rats than they were in adults but were indistinguishable from them by 16 days of age, indicating that the heart is less sensitive to β‐adrenoceptor stimulation early in neonatal life.
The ontogeny of sympathetic control of heart rate in the rat depends upon maturational changes in both presynaptic and postsynaptic elements.
TIME‐DEPENDENT STIMULATORY AND INHIBITORY EFFECTS OF PROSTAGLANDIN Ex ON EXUDATIVE AND TISSUE COMPONENTS OF GRANULOMATOUS INFLAMMATION IN RATS
Authors: BONTA I.L. , PARNHAM M.J. 
Published: July 2012

The effects of prostaglandin (PGE1), following local administration during different phases of developing sponge‐induced granulomata, were studied in normal and essential fatty acid deficient (EFAD) rats.
In normal rats, a single dose of 1 μg PGE1 on implantation (day 1) increased exudate production without altering total leucocyte counts after 6 h and stimulated granulomatous tissue formation after 8 days.
Repeated daily administration of the same dose of PGEX on days 1 to 3 had no effect, while administration on days 4 to 7 (i.e. when tissue growth is already in progress) inhibited granuloma formation.
In EFAD rats, which are known to produce only very small amounts of endogenous prostaglandins, acute (6 h) exudate formation was unaffected by 0.05 μg PGEj. However, early stimulatory and later inhibitory effects of 0.05 μg PGE1 per day were obtained on the granulomatous tissue, similar to those obtained with the 20 fold higher dose in normal rats.
The early stimulatory action of PGEX on granulomatous tissue formation was enhanced, in normal rats, by concomitant administration of 10 jag theophylline. This latter compound did not influence the later inhibitory effect of PGEj.
These results indicate that PGE1 exerts either pro‐ or anti‐inflammatory actions on the proliferative (tissue) component of the inflammatory process, depending on the time of administration. While the stimulatory effect following early administration may have been secondary to an initial cyclic adenosine 3′, 5′‐monophosphate‐mediated, vascular response, such a mechanism is unlikely to have been responsible for the later anti‐inflammatory action of PGEj.
The implications of these results are discussed in relation to the postulated negative‐feedback role of endogenous PGE in chronic inflammation.
THE EFFECT OF PARGYLINE AND DESMETHYLIMIPRAMINE ON MONOAMINE CONCENTRATIONS AND AMPHETAMINE‐INDUCED GLYCOGENOLYSIS IN THE MOUSE BRAIN
Authors: HUTCHINS D.A. 
Published: July 2012

Pargyline (100 mg/kg) increased the concentration of cerebral noradrenaline dopamine and 5‐hydroxytryptamine in the mouse. Amphetamine (5 mg/kg) reduced the concentration of noradrenaline and increased the concentrations of 5‐hydroxytryptamine and dopamine.
When amphetamine was administered 4 h after an injection of pargyline, the effect of the sympathomimetic drug on the concentrations of noradrenaline and 5‐hydroxytryptamine was not altered. The effect on the dopamine content was reversed, amphetamine causing a decrease instead of an increase.
Pargyline increased the concentration of cerebral glycogen, whereas amphetamine caused a decrease.
The administration of amphetamine 4 h after pargyline resulted in a decrease in brain glycogen similar to that seen after amphetamine alone.
These results suggest that the potentiation of the effect of amphetamine on animal behaviour by pretreatment with an inhibitor of monoamine oxidase is not mediated through a central action on noradrenaline release.
Amphetamine‐induced glycogenosis was antagonized by 71% by desmethylimipramine (10 mg/kg).
The change in glycogen concentration as a function of time after an injection of amphetamine was not modified when 2 consecutive doses of amphetamine were given with an interval between doses of 30 minutes.
PHARMACOLOGICAL PROPERTIES OF ACETYLCHOLINE‐INDUCED EXCITATION OF SUBTHALAMIC NUCLEUS NEURONES
Authors: FEGER JEAN , HAMMOND CONSTANCE , ROUZAIRE‐DUBOIS BEATRICE 
Published: July 2012

In 15 rats anaesthetized with ketamine, microiontophoretically applied acetylcholine (ACh) excited all 58 cells studied in the subthalamic nucleus (STN).
The ACh‐evoked excitation was slow in onset and outlasted the ACh application. There was no sign of desensitization when the ACh application was prolonged or repeated. The excitation was prolonged by a concomitant application of physostigmine.
Acetyl‐β‐methyl choline and oxotremorine were effective cholinomimetics. Nicotine had no effect.
The ACh excitation was antagonized by atropine and scopolamine but not by mecamylamine.
It was concluded that STN ACh receptors are muscarinic in character.
Since large microiontophoretic applications of Mg2+ did not suppress ACh‐evoked excitation, it is suggested that ACh acts postsynaptically.
The excitatory response of STN cells to striatal or pallidal stimulation was unaffected by atropine administered either microiontophoretically to single cells or intravenously (3 mg/kg) to the whole animal.