bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE PHARMACOLOGY OF ADRENERGIC NEURONAL RESPONSES IN THE CEREBRAL CORTEX: EVIDENCE FOR EXCITATORY α‐ AND INHIBITORY β‐RECEPTORS
Authors: BEVAN P. , BRADSHAW C.M. , SZABADI E. 
Published: July 2012

The technique of microelectrophoresis was used to compare the actions of a range of adrenoceptor agonists on single cortical neurones in the rat anaesthetized with halothane.
Phenylephrine and methoxamine were exclusively excitatory, whereas salbutamol was entirely depressant. Noradrenaline and isoprenaline could evoke both excitatory and depressant responses. Lower doses of isoprenaline usually evoked depressions, whereas higher doses, on the same cell, evoked excitatory responses.
The α‐adrenoceptor blocking agents, phentolamine and phenoxybenzamine, reversibly antagonized excitatory responses to adrenoceptor agonists, without affecting depressant responses to adrenoceptor agonists or excitatory responses to acetylcholine.
The β‐adrenoceptor blocking agents, propranolol and sotalol, reversibly antagonized both depressant and excitatory responses to adrenoceptor agonists, without affecting responses to acetylcholine. When the effect of sotalol on excitatory and depressant responses to adrenoceptor agonists was compared on the same cell, the depressant responses could be selectively antagonized, without affecting the excitatory responses.
It is concluded that (a) responses of cortical neurones to adrenoceptor agonists are mediated by both α‐ and β‐receptors; (b) these α‐ and β‐receptors give rise to opposite effects: the α‐receptors being excitatory and the β‐receptors being inhibitory; and (c) responses of many neurones reflect the presence of both types of receptor.
THE EFFECTS OF NON‐STEROIDAL ANTI‐INFLAMMATORY DRUGS ON CHOLINERGIC AND HISTAMINE‐INDUCED CONTRACTIONS OF GUINEA‐PIG ISOLATED ILEUM
Authors: FAMAEY J.P. , FONTAINE J. , REUSE J. 
Published: July 2012

Eleven non‐steroidal anti‐inflammatory drugs (NSAID) reversibly inhibited contractions of the longitudinal muscle of the guinea‐pig isolated ileum induced by acetylcholine, histamine, electrical transmural stimulation and nicotine in this order of increasing potency.
After the addition of prostaglandins E1, E2 or F2α, with partially effective concentrations of NSAID (but not with higher concentrations which almost totally prevented the responses) the inhibitory effects of NSAID were reversibly lost, except for electrically induced contractions and prostaglandin F2α.
The effects of NSAID may be due to actions on biological membranes or on distribution of ions in addition to their inhibitory effect on prostaglandin synthesis. Prostaglandins may reverse the inhibition by non‐selective sensitization of smooth muscle to various agonists.
DISSIMILARITY BETWEEN THE RESPONSES TO ADENOSINE TRIPHOSPHATE OR ITS RELATED COMPOUNDS AND NON‐ADRENERGIC INHIBITORY NERVE STIMULATION IN THE LONGITUDINAL SMOOTH MUSCLE OF PIG STOMACH
Authors: OHGA A. , TANEIKE T. 
Published: July 2012

Transmural electrical stimulation (TMS) of longitudinal smooth muscle strips taken from the cardiac portion of the pig stomach produced biphasic responses consisting of initial contractions followed by relaxations. The excitatory component was enhanced by neostigmine and abolished by atropine. After atropine treatment, TMS and nicotine or 1,1‐dimethyl‐4‐phenyl‐piperazinium, caused a relaxation or a relaxation followed by an after‐contraction. All of these responses were abolished or reduced reversibly with tetrodotoxin and cocaine, while hexamethonium only abolished the response to ganglion‐stimulating agents.
The relaxation caused by TMS reached a maximum amplitude at 5–10 Hz, and was entirely resistant to the effects of α‐ and β‐adrenoceptor blocking agents, or a combination of them, and also to guanethidine. These results strongly suggested that the relaxation was elicited by stimulation of intramural non‐adrenergic inhibitory neurones.
In the presence of atropine and guanethidine, adenosine triphosphate (ATP, 5–20 μM) caused only a tonic contraction, and ATP (25–200 μM) or adenosine diphosphate (25–200 μM) produced a contractile response or a biphasic one (tonic contraction preceded by a slight relaxation). Adenosine monophosphate and adenosine caused only the tonic contraction over the range of concentrations (25–200 μM).
Stimulation of the intramural inhibitory neurones of the tissue consistently evoked an inhibitory junction potential, which showed a summation during repetitive stimulation. One the other hand, ATP elicited mainly a small depolarization of a few mV.
When the desensitization to ATP of the muscle was achieved in the presence of atropine and guanethidine, the relaxation induced by stimulation of the non‐adrenergic inhibitory neurones could be evoked without any modification.
Dipyridamole neither potentiated the inhibitory responses due to stimulation of the intramural inhibitory neurones nor showed any consistent effect on the ATP‐induced response.
From these results, it is unlikely that ATP, or any related compound, is the transmitter substance of the intramural inhibitory neurones in the longitudinal smooth muscle of the pig stomach.
MECHANISM OF NICOTINE‐INDUCED RELEASE OF NORADRENALINE FROM ADRENERGIC NERVE ENDINGS
Authors: JAYASUNDAR S. , VOHRA M.M. 
Published: July 2012

A study of the mechanism of release of [3H]‐noradrenaline ([3H]‐NA) by nicotine from isolated vas deferens of the rat was made using incubation media of different ionic composition.
Nicotine (20 μg/ml)‐induced release of [3H]‐NA was significantly potentiated in K+‐free Krebs solution as compared to that in normal Krebs‐Ringer solution.
Nicotine‐induced release of [3H]‐NA was significantly reduced in Na+‐deficient Krebs solution (containing only 11 mM Na+) and was abolished in Na+‐free Krebs solution.
In totally depolarized tissues, nicotine failed to cause an outflow of [3H]‐NA but Ca2+ (5 mM) did so.
Nicotine required the presence of Ca2+ in the incubation medium to cause release of [3H]‐NA from adrenergic nerve terminals, the magnitude of release being dependent upon the concentration of Ca2+.
Nicotine‐induced release of [3H]‐NA was demonstrated in high Ca2+, Na+‐free Krebs solution in which all Na+ had been replaced with Ca2+.
It is concluded that nicotine increases the membrane permeability to both Na+ and Ca2+. It is also suggested that the increase in permeability to Ca2+ alone is not sufficient but a local depolarizing action of nicotine is necessary to cause release of noradrenaline from adrenergic nerve endings.
THE EFFECTS OF INTRAVENOUS ANAESTHETICS ON THE CARDIOVASCULAR SYSTEM OF THE RABBIT
Authors: McGRATH J.C. , MacKENZIE J.E. 
Published: July 2012

A pithed rabbit preparation is described that allows selective stimulation of the vertebral outflows.
The responses to stimulation of sympathetic vasopressor fibres were blocked by hexamethonium and phentolamine but potentiated by cocaine, whereas the responses to stimulation of cardio‐accelerator fibres were blocked by propranolol.
Ketamine, althesin and pentobarbitone enhanced the effects of noradrenaline and attenuated the effects of sympathetic nerve stimulation. Thiopentone enhanced the effects of both noradrenaline and sympathetic nerve stimulation.
In pithed rabbits a transient, dose‐related cardiovascular depression was produced by each agent irrespective of whether vasomotor tone was present whereas in decerebrate rabbits the corresponding cardiovascular depression was longer lasting.
It is concluded that the cardiovascular depression produced by intravenous anaesthetics in intact rabbits is due to a combination of central and peripheral effects.
CENTRAL AND PERIPHERAL NORADRENALINE IN THE TWO KIDNEY MODEL OF RENOVASCULAR HYPERTENSION IN THE RAT
Authors: DARGIE H.J. , FRANKLIN S.S. , REID J.L. 
Published: July 2012

Plasma noradrenaline concentrations were similar in rats following unilateral renal arterial constriction (two kidney Goldblatt model) and in sham‐operated control rats.
The development of hypertension was not affected by pretreatment with intracisternal injections of 6‐hydroxydopamine.
These data suggest that sympathetic mechanisms do not contribute to the development of hypertension in this model.
THE RELATIONSHIP BETWEEN ENERGY METABOLISM AND THE ACTION OF INHIBITORS OF HISTAMINE RELEASE
Authors: GARLAND L.G. , JOHANSEN T. 
Published: July 2012

Dextran‐induced release of histamine from rat mast cells was inhibited equally in complete and glucose‐free Tyrode solution by doxantrazole (0.03‐3 μmol/l), theophylline (0.1–3 mmol/l) and dicumarol (0.01–10 μmol/litre).
Doxantrazole (3 μmol/l), theophylline (3 mmol/l) and dicumarol (10 μmol/l) did not reduce the adenosine 5′‐triphosphate (ATP) content of mast cells in glucose‐free medium. Higher concentrations of dicumarol (56–100 μmol/l) markedly reduced the cellular ATP content. This reduction was reversed by glucose.
Papaverine was a more potent inhibitor of histamine release from mast cells incubated in glucose‐free solution than in complete Tyrode solution (dose‐ratio = 20). Like antimycin A (1 μmol/l), papaverine (3 μmol/l) caused a depletion of mast cell ATP that was greater in the absence (85%) than in the presence (25%) of extracellular glucose.
These results suggest that dicumarol, like doxantrazole and theophylline, inhibits histamine release without affecting mast cell energy metabolism. In contrast, papaverine probably inhibits release by depleting ATP that is required for exocytosis.
Inhibition of histamine release by dibutyryl cyclic adenosine 3,5′‐monophosphate (1–3 mmol/l) was significantly greater when cells were incubated in complete rather than in glucose‐free medium.
RESPONSES OF MOTONEURONES TO ELECTROPHORETICALLY APPLIED DOPAMINE
Authors: BARASI S. , ROBERTS M.H.T. 
Published: July 2012

The effect of electrophoretically applied dopamine upon motoneurone excitability has been investigated. Field potentials originating from antidromically activated motoneurones were recorded from the ventral horn of the rat lumbar spinal cord.
Field potentials showed an increase in amplitude following electrophoretic application of dopamine. Dopamine was shown to be less potent than noradrenaline and 5‐hydroxytryptamine in producing these changes.
Measurement of the transport number of dopamine suggests that the relatively low potency of dopamine cannot be attributed to differences in ionic mobilities between the amines.
Electrophoretic application of α‐flupenthixol was shown to discriminate between dopamine and 5‐hydroxytryptamine responses. Dopamine responses were profoundly reduced.
Electrophoretically applied α‐flupenthixol also discriminated between dopamine and noradrenaline. Noradrenaline responses were consistently potentiated by α‐flupenthixol. The possibility is discussed that dopamine may not merely be a precursor for noradrenaline in the rat spinal cord.
THE GENERATION OF NERVE AND MUSCLE REPETITIVE ACTIVITY IN THE RAT PHRENIC NERVE‐DIAPHRAGM PREPARATION FOLLOWING INHIBITION OF CHOLINESTERASE BY ECOTHIOPATE
Authors: MORRISON J.D. 
Published: July 2012

Simultaneous extracellular recordings were made from two end‐plate zones of the isolated diaphragm and from the phrenic nerve of the rat in response to stimulation of the nerve. The contractions of the diaphragm were also recorded.
In the curarized diaphragm, the introduction of ecothiopate, a non‐competitive inhibitor of cholinesterase, caused a threefold increase in the amplitude of the end‐plate current and an eightfold increase in the duration at half the peak amplitude.
In the non‐curarized diaphragm, the introduction of ecothiopate caused the generation of repetitive activity (RA) in first the phrenic nerve: this was then followed by RA in the diaphragm. At that stage, nerve RA possessed a shorter latency than muscle RA. The generation time for nerve RA was 1.6 ms and for mRA, it was 2.7 milliseconds.
Nerve RA was more labile than muscle RA; it was readily abolished by increasing the frequency of stimulation, by magnesium, by tubocurarine or by high concentrations of ecothiopate, whereas muscle RA was still generated. Steady exposure to acetylcholine abolished both forms of RA.
Two competitive inhibitors of cholinesterase, neostigmine and ambenonium, were also shown to evoke RA in nerve and muscle. The generation times for nerve RA and muscle RA were similar to those following ecothiopate.
It was concluded that nerve RA and muscle RA were generated after the inhibition of cholinesterase by ecothiopate as a result of the prolonged action of acetylcholine upon cholinoceptive sites on the nerve terminal and motor endplate respectively. A direct excitatory action of ecothiopate upon the phrenic nerve terminals was excluded.
THE EFFECT OF Δ9‐TETRA‐HYDROCANNABINOL ON BODY TEMPERATURE AND BRAIN AMINE CONCENTRATIONS IN THE RAT AT DIFFERENT AMBIENT TEMPERATURES
Authors: FENNESSY M.R. , TAYLOR D.A. 
Published: July 2012

Rats were injected intravenously with 2 mg/kg (–)‐trans‐Δ9‐tetrahydrocannabinol (Δ9‐THC) at ambient temperatures of 4°, 21°, 31° and 37°C.
The general behaviour exhibited by rats treated with Δ9‐THC was similar at all four ambient temperatures.
Body temperatures were recorded continuously before and after drug administration. At 4° and 21°C, Δ9‐THC caused hypothermia whereas no change in body temperature occurred at 31° and 37°C.
The concentrations in the whole brain of noradrenaline (NA), dopamine, 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) were determined spectrophotofluorimetrically 1 h after drug administration. At 4°C Δ9‐THC caused an increase of 5‐HT, at 21°C an increase of 5‐HIAA, at 31°C an increase of 5‐HIAA and a decrease of NA, and at 37°C an increase of 5‐HT and 5‐HIAA.
At all ambient temperatures, Δ9‐THC increased the brain levels of 5‐HT and/or 5‐HIAA. A correlation between the Δ9‐THC‐induced hypothermic response and the possible alteration of brain 5‐HT metabolism cannot be excluded.
THE EFFECTS OF ADENINE NUCLEOTIDES ON CUTANEOUS AFFERENT NERVE ACTIVITY
Authors: BLEEHEN TIRZA 
Published: July 2012

The activity produced by the adenine nucleotides adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) and by potassium, acetylcholine (ACh), 5‐hydroxytryptamine (5‐HT) and bradykinin when applied to an exposed blister base on the ear of anaesthetized rabbits or intra‐arterially to anaesthetized cats was investigated in multiple strands dissected from the auricular‐temporal and saphenous nerves of rabbits and cats, respectively.
In the rabbit preparation potassium and the adenine nucleotides produced activity in the nerve fibres. The effects of these substances were produced in comparable dose ranges; threshold effects being produced by potassium at a concentration of 13 mm and by ADP at a concentration of 4 mm. ACh, 5‐HT and bradykinin were inactive at similar or higher concentrations.
In the cat preparation all the substances tested produced activity in the nerve fibres. The adenine nucleotides were comparatively less potent than ACh, 5‐HT or bradykinin, but had greater potency than potassium.
It was concluded that the adenine nucleotides do possess effects on afferent nerve terminals or fibres and thus resemble other known algogenic substances such as potassium, ACh, 5‐HT and bradykinin.
A 5‐HYDROXYTRYPTAMINE‐LIKE MODE OF ANORECTIC ACTION FOR 6‐CHLORO‐2‐[1‐PIPERAZINYL]‐PYRAZINE (MK‐212)
Authors: CLINESCHMIDT BRADLEY V. , McGUFFIN JODIE C. , PFLUEGER A. BARBARA , TOTARO JAMES A. 
Published: July 2012

The mechanism of the reduction in food consumption elicited by 6‐chloro‐2‐[1‐piperazinyl]‐pyrazine (MK‐212) administered systemically was investigated in the rat. (+)‐Fenfluramine and (+)‐amphetamine were included in some studies for comparative purposes.
Pretreatment with methergoline, a 5‐hydroxytryptamine (5‐HT) antagonist, reduced the magnitude of the anorectic effect of 1.5 and 3 mg/kg of MK‐212, while the anti‐5‐HT agents, cyproheptadine and cinanserin, were likewise effective against the 3 mg/kg dose.
Xylamidine, an antagonist of 5‐HT that penetrates poorly into the central nervous system, completely blocked the decrease in food intake caused by 5‐HT administered peripherally, while not antagonizing an equianorectic dose of MK‐212.
Reduction of brain 5‐HT by intraventricular injection of 5,6‐dihydroxytryptamine, intraperitoneal administration of p‐chloroamphetamine or placement of a lesion in the region of the median raphe nucleus diminished the anorectic response to 3 mg/kg of MK‐212. The anorectic effect of amphetamine was reduced by p‐chloroamphetamine or lesion in the raphe, but not by 5,6‐dihydroxytryptamine. The decrease in food consumption produced by 1.5 mg/kg of MK‐212 was antagonized by prior treatment with p‐chloroamphetamine, but not by 5,6‐dihydroxytryptamine.
Haloperidol, which blocks receptors for dopamine, antagonized the anorexigenic effect of amphetamine, but was ineffective in offsetting the action of MK‐212, 3 mg/kg.
Pretreatment with chlorimipramine to inhibit the 5‐hydroxytryptaminergic uptake mechanism did not affect the anorectic response to 3 mg/kg of MK‐212, whereas the response to fenfluramine was diminished.
The results indicate that the anorectic action of MK‐212 involves a 5‐HT‐like component which is more evident at the higher dose level of the compound. The anorexigenic property of MK‐212 may depend, at least partly, upon the integrity of 5‐HT‐containing neurones in the central nervous system.
SPECIES DIFFERENCES IN POSTGANGLIONIC MOTOR TRANSMISSION TO THE RETRACTOR PENIS MUSCLE
Authors: AMBACHE N. , KILLICK S.W. 
Published: July 2012

Graded motor responses were elicited in isolated, desheathed, thin strips of dog, horse, pig and sheep retractor penis (RP) muscles by field stimulation with trains of 0.2 ms pulses at 10 hertz. These twitches were shown to be neurogenic in all four species, by their prompt extinction in tetrodotoxin.
α‐Adrenoceptor blocking drugs abolished the contractile response to noradrenaline and to tyramine in all four species.
Motor transmission was wholly adrenergic in the horse as in the dog RP because phentolamine rapidly abolished the electrically induced twitches in both these species; but in the pig and in the sheep RP a large proportion of the motor transmission was unaffected by phentolamine given in many times the concentration required to abolish matching noradrenaline‐induced contractions.
Because of the occurrence of periodic spasms in sheep preparations, further investigation of the phentolamine‐resistant transmission was confined to the pig RP. Its responses were shown to be entirely postganglionic in origin because they were unaffected by pentolinium.
In the pig RP a considerable proportion of the phentolamine‐resistant motor transmission persisted after combined blockade of α‐ and β‐adrenoceptors by phenoxybenzamine plus propranolol and was more resistant to guanethidine and bretylium than the motor transmission to the dog RP; it was not extinguished after reserpine treatment.
The pig RP is contracted by histamine but is rather insensitive to acetylcholine, 5‐HYDROXYTRYPTAMINE and adenosines‐triphosphate. The motor transmission remained unaffected after responses to these substances were blocked by the following antagonists, given alone or in combination: mepyramine, burimamide, atropine, (+)‐tubocurarine, methysergide and 2–2′‐pyridylisatogen tosylate.
ROLE OF PLATELETS IN ASPIRIN‐SENSITIVE BRONCHOCONSTRICTION IN THE GUINEA‐PIG; INTERACTIONS WITH SALICYLIC ACID
Authors: LEFORT JEAN , VARGAFTIG BERNARDO B. 
Published: July 2012

The bronchoconstriction caused in the guinea‐pig by arachidonic acid (AA), bradykinin, adenosine diphosphate (ADP) and adenosine triphosphate (ATP) was correlated with effects on platelets. ATP and ADP produced a brief thrombocytopenia and AA a more prolonged one. Bradykinin had no effect on platelets.
Aspirin inhibited bronchoconstriction and thrombocytopenia produced by AA and part of the bronchoconstriction produced by ATP, but had no effect against ADP. Thrombocytopenia produced by ADP and ATP was not affected by aspirin or indomethacin.
Platelet depletion by antiserum prevented bronchoconstriction in response to ADP and to ATP, but not in response to bradykinin or to AA, showing that platelets are not involved in aspirin‐sensitive bronchoconstriction. Infusions of ADP reduced bronchoconstriction and thrombocytopenia in response to ADP itself and to ATP, but not to AA. Bronchoconstriction by ADP or ATP involves an action on platelets. Only that due to ATP is partially dependent on the activity of prostaglandin synthetase.
ATP induced aggregation in vitro in guinea‐pig platelet‐rich plasma (PRP). Rabbit PRP responded only when ATP was first incubated with guinea‐pig plasma. The aggregating compound formed was probably ADP, since it was destroyed by apyrase. Its formation was not inhibited by aspirin or indomethacin, indicating that aspirin inhibits ATP‐induced bronchoconstriction by a different mechanism.
The aggregating effect of ATP on guinea‐pig platelets was inhibited by concentrations of apyrase that block ADP‐induced aggregation, and potentiated by lower concentrations of apyrase.
Adenosine 5′‐tetraphosphate did not aggregate platelets in vivo or in vitro. In vitro aggregation occurred when apyrase was added, suggesting transformation into ADP. Adenosine 5′‐tetraphosphate and apyrase inhibited aggregation due to ADP, but failed to affect that due to AA. This suggests that aggregation involving products of prostaglandin synthesis does not require ADP.
Salicylic acid did not interfere with bronchoconstriction or aggregation due to AA, but prevented inhibition by aspirin when the weight ratio, salicylic acid:aspirin was 4:1. Salicylic acid may be useful in studies of potential inhibitors of thromboxane A2 synthesis and of thromboxane A2‐depen‐dent processes in vivo and in vitro.
HYPERTHERMIC RESPONSES TO CENTRAL AND PERIPHERAL INJECTIONS OF MORPHINE SULPHATE IN THE CAT
Authors: CLARK WESLEY G. , CUMBY H. RICK 
Published: July 2012

The effect of morphine on body temperature was studied in conscious, unrestrained cats provided with implanted third or lateral cerebral ventricular cannulae, jugular venous catheters and retroperitoneal thermocouples.
Intraventricular injections of 2.5–50 μg and intravenous injections of 1–10 mg/kg morphine sulphate produced dose‐related hyperthermic responses. Similar mean increases in body temperature after administration of a given dose were elicited in cats which had not previously received morphine and, provided that tolerance was avoided by spacing injections at least 72 h apart, in cats which received a series of injections of morphine. Morphine was at least 850 times more potent when injected into the third ventricle than when given intravenously. Increasing the dose of morphine sulphate injected into the third ventricle to 1250 μg only prolonged the hyperthermia. Morphine did not produce hypothermia at any dose tested.
Injection of 10 μg morphine sulphate into the third ventricle produced similar hyperthermias at ambient temperatures (tas) of 4–6, 21–23 and 33–36°C. The increase in body temperature was associated with shivering at the lower tas. At the highest ta, shivering was not evoked, but respiratory rate decreased after morphine if it was initially elevated. These results suggest that morphine increased the level at which body temperature was regulated.
Neither metiamide nor indomethacin antagonized morphine so histamine and prostaglandins were apparently not required for the hyperthermic effect.