bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF MOLINDONE AND FLUPHENAZINE ON THE BRAIN CONCENTRATION OF SOME PHENOLIC AND CATECHOLIC AMINES IN THE MOUSE AND THE RAT
Authors: JUORIO A.V. 
Published: July 2012

The concentrations of p‐ and m‐tyramine, dopamine, 3,4‐dihydroxyphenylacetic acid and homovanillic acid were measured in the mouse or rat striatum following the subcutaneous injection of molindone or fluphenazine. The mouse hypothalamic levels of the m‐ or p‐isomers of octopamine were also analysed.
Endogenous concentrations of p‐ and m‐tyramine in the mouse striatum and p‐ and m‐octopamine in the mouse hypothalamus were 20.6, 5.7, 9.4 and 1.2ng/g respectively. The rat striatum concentrations of p‐ and m‐tyramine were 12.8 and 3.8 ng/g.
The administration of low doses of molindone (1 to 10 mg/kg) produced a reduction in striatal p‐tyramine, an increase in m‐tyramine and an increase in dopamine turnover. Similar effects were produced by all doses of fluphenazine (0.1 to 5 mg/kg) employed. These findings are consistent with those observed after blockade of dopamine postsynaptic receptors.
With high doses of molindone (100 mg/kg) the effects on both tyramines and on dopamine metabolism were reversed. These results can be interpreted as molindone acting as a partial agonist.
The concentrations of hypothalamic p‐ and m‐octopamine were increased by the higher doses of molindone (20 to 100 mg/kg) employed while lower doses produced no significant effects. All doses of fluphenazine reduced hypothalamic p‐octopamine. These changes seem to depend on differences in the availability of p‐tyramine to be converted into p‐octopamine.
These results suggest that molindone acts as a blocker or a partial agonist of dopamine receptor sites and fit well with the proposal of a reciprocal relation between dopamine and tyramine. It is not possible yet to ascertain whether tyramine controls dopamine or vice versa or if it is a direct or a more remote relation.
INTRACELLULAR OBSERVATIONS ON THE EFFECTS OF MUSCARINIC AGONISTS ON RAT SYMPATHETIC NEURONES
Authors: BROWN D.A. , CONSTANTI A. 
Published: July 2012

Responses of single neurones in isolated superior cervical ganglia of the rat to muscarinic agonists were recorded with intracellular microelectrodes.
(±)‐Muscarine (1 to 10 μm) and methylfurmethide (1 to 3 μm) produced reversible membrane depolarizations (≤ 15 mV) accompanied by a fall in input conductance and an increased tendency toward repetitive spike discharges. The spike configuration was unchanged.
Analysis of steady‐state current/voltage curves revealed the most consistent muscarinic effect to be a large reduction (∼50% at 10 μm muscarine) in input slope conductance around rest potential. This conductance decrease diminished as the membrane was hyperpolarized, and the normal increase in slope conductance with membrane depolarization was depressed. The current/voltage curves in the presence and absence of agonist did not usually intersect; in a few tests, the curves intersected at between −65 and −88 mV (i.e. 9 to 28 mV hyperpolarized to rest potential).
Divalent cations (10 mm [Ca2+] or [Mg2+]) showed a small muscarine‐like effect on the current/voltage and slope conductance/voltage curves, but did not affect the action of muscarine itself.
Tetraethylammonium (TEA, 5 mm) also had a small muscarine‐like effect, and depressed or reversed the action of muscarine. However, TEA differed from muscarine in blocking orthodromic transmission and prolonging direct spike repolarization.
It is concluded that the primary effect of muscarinic agonists is to alter the rectifying properties of the cell within the potential range −80 to −40 mV.
γ‐AMINOBUTYRIC ACID AGONISTS: AN in vitro COMPARISON BETWEEN DEPRESSION OF SPINAL SYNAPTIC ACTIVITY AND DEPOLARIZATION OF SPINAL ROOT FIBRES IN THE RAT
Authors: ALLAN R.D. , EVANS R.H. , JOHNSTON G.A.R. 
Published: July 2012

Relative molar potencies, of a range of γ‐aminobutyrate (GABA)‐related agonists, for depolarization of isolated spinal roots have been compared with their potencies for depression of spontaneous synaptic activity, recorded in ventral roots of hemisected spinal cord preparations from 3 to 9‐day‐old rats. Both effects were sensitive to antagonism by bicuculline.
The depolarizing potencies of the series were not parallelled by their depressant potencies. This disparity was shown most strongly by 4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridin‐3‐ol (THIP) which was 20 times stronger than GABA in depolarizing root fibres and 20 times stronger than GABA in its depressant action and by (+)‐cis‐3‐aminocyclopentane‐carboxylic acid (17 times weaker than GABA on root fibres and 42 times stronger than GABA as a depressant).
The effect of uptake on these relative potencies is discussed and it is concluded that fibre depolarization and depression are probably mediated by different types of bicuculline‐sensitive receptor.
The depolarizing potencies of the agonists showed a strong correlation with previously reported data for displacement of labelled GABA from in vitro rat brain membrane preparations (correlation coefficient 0.90, P < 0.001). However, the relative depressant potencies showed no such correlation with binding data (correlation coefficient 0.50, P > 0.05).
EFFECT OF MIANSERIN ON NORADRENERGIC TRANSMISSION IN THE RAT ANOCOCCYGEUS MUSCLE
Authors: DOGGRELL SHEILA A. 
Published: July 2012

The effects of mianserin on the accumulation of (−)‐[3H]‐noradrenaline and on contractile responses to field stimulation, exogenously applied (−)‐noradrenaline, and to tyramine were studied in the rat anococcygeus muscle.
Mianserin (10−9to 10−5m) and nortriptyline (10−9to 10−5m) inhibited the accumulation of (−)‐[3H]‐noradrenaline. In this aspect mianserin had a similar potency to nortriptyline, the most potent tricyclic antidepressant in inhibiting noradrenaline accumulation in this tissue.
Mianserin 10−9or 10−8m alone had no effect on contractile responses to field stimulation and to (−)‐noradrenaline but inhibited the responses to tyramine. The responses to field stimulation at low frequencies and to (−)‐noradrenaline were potentiated by 10−7and 10−6m mianserin. It is suggested that the inhibitory effect mianserin has on neuronal accumulation is primarily responsible for these effects. Mianserin 10−5m inhibited responses to field stimulation and to (−)‐noradrenaline.
In the presence of nortriptyline (10−6m), the contractile responses to field stimulations were potentiated by mianserin (10−8, 10−7and 10−6m), 10−8m being the most potent in this aspect. Mianserin 10−8, 10−7, 10−6and 10−5m had a similar inhibitory effect on responses to (−)‐noradrenaline. In the absence of neuronal uptake, the potentiating effect of mianserin on responses to field stimulation may be due to antagonism at presynaptic α‐adrenoceptors. In the presence of 10−6m nortriptyline, 10−5m mianserin abolished responses to field stimulation.
Following incubation of the tissue in the presence of 6‐hydroxydopamine (10−3m for 3 h), mianserin (10−7, 10−6and 10−5m) nortriptyline (10−7and 10−6m) and phentolamine (5 × 10−8and 5 × 10−7m) inhibited contractile responses to (−)‐noradrenaline. This illustrates the ability of these agents to inhibit the responses to noradrenaline at a postsynaptic site. The inhibitory effect was dose‐related with nortriptyline and phentolamine; this illustrates the ability of these agents to antagonize postsynaptic α‐adrenoceptors. The inhibitory effect observed with mianserin was not dose‐related. This suggests that in addition to its reported ability to antagonize postsynaptic α‐adrenoceptors, mianserin may have another post‐synaptic action at the level of, or distal to, the α‐adrenoceptor.
These results illustrate that, in the rat anococcygeus muscle, mianserin is a potent inhibitor of noradrenaline accumulation and may be an antagonist at presynaptic α‐adrenoceptors. Mianserin also inhibits the responses to exogenously applied noradrenaline in this tissue by an action or actions at the level of, or distal to, the postsynaptic α‐adrenoceptor.
INFLUENCE OF CELLULAR TRANSPORT ON THE INTERACTION OF AMINO ACIDS WITH γ‐AMINOBUTYRIC ACID (GABA)‐RECEPTORS IN THE ISOLATED OLFACTORY CORTEX OF THE GUINEA‐PIG
Authors: BROWN D.A. , COLLINS G.G.S. , GALVAN M. 
Published: July 2012

Freshly cut guinea‐pig olfactory cortex slices contained 2.2 mmol γ‐aminobutyric acid (GABA)/kg tissue weight. This declined during in vitro incubation at 25°C in the absence of exogenous GABA, but increased to 6.95 mmol/kg after 1.5 h incubation in 1 mm GABA.
Uptake of [3H]‐GABA (1 μm) was inhibited by 1 mm (±)‐nipecotic acid (−83%), β‐amino‐n‐butyric acid (BABA) (−59%), l‐2,4‐diaminobutyric acid (DABA) (−63%), (±)cis‐3‐aminocyclohexane carboxylic acid (ACHC) (−53%), and 3‐aminopropanesulphonic acid (3‐APS) (−26%), but was increased by β‐alanine (BALA) (+23%).
Autoradiographs showed steep concentration gradients of radioactivity across slices incubated for short periods in [3H]‐GABA.
Efflux of [3H]‐GABA from pre‐loaded slices was accelerated strongly by nipecotic acid, BABA, DABA and ACHC but weakly or not all by BALA or 3‐APS.
Nipecotic acid (1 mm) potentiated the surface‐depolarization of the slice produced by GABA but not that produced by 3‐APS.
The depolarizing actions of DABA, BABA, nipecotic acid and ACHC, but not that of 3‐APS or BALA, were potentiated when the endogenous GABA content of slices was raised.
It is concluded that: (a) the depolarizing action of exogenous GABA is limited by cellular uptake; (b) surface‐depolarizations produced by nipecotic acid, DABA, BABA and ACHC may be mediated by the release of GABA; and (c) neuronal, rather than glial, transport systems are responsible for these effects.
CENTRAL RESPIRATORY AND CIRCULATORY DEPRESSION CAUSED BY INTRAVASCULAR SAXITOXIN
Authors: BORISON H.L. , CULP W.J. , GONSALVES S.F. , McCARTHY L.E. 
Published: July 2012

In cats anaesthetized with pentobarbitone and vagotomized, observations were made on the phrenic nerve action potential and the diaphragm electromyogram (EMG) at constant end‐tidal Pco2. Arterial blood pressure was stabilized by intravenous infusions of noradrenaline.
Intravenous administration of saxitoxin (STX) initially abolished respiratory activity in the EMG and caused a slowing of oscillation in the central phrenic neurogram. Additional STX produced apneustic phrenic discharges followed by a progressive loss of nerve action potentials.
The inspiratory centre in the medulla oblongata was stimulated electrically to evoke a sustained phrenic nerve discharge. STX, given intravenously, resulted in the elimination of spontaneous nerve activity without interfering with the evoked response.
The cephalic intravascular infusion of STX into a carotid or vertebral artery depressed spontaneous respiratory activity while sparing EMG activity evoked by electrical stimulation of the intact phrenic nerve.
Spontaneous respiratory discharge in the phrenic nerve was eliminated by smaller doses of STX administered intra‐arterially than were required intravenously. In addition, onset of and recovery from neural silence occurred faster following intra‐arterial injection of STX.
Depressant effects on arterial blood pressure coincided with those on respiration when STX was given intra‐arterially.
An electrophysiological assay on frog sartorius muscle was used to measure STX in the cerebrospinal fluid. Levels of STX detected were proportional to amounts of the toxin infused intra‐arterially.
It is concluded that STX exchanges rapidly between blood and brain to bring about central depression and this adds to its peripheral paralytic actions.
COMPARISON OF MIANSERIN WITH DESIPRAMINE, MAPROTILINE AND PHENTOLAMINE ON CARDIAC PRESYNAPTIC AND VASCULAR POSTSYNAPTIC α‐ADRENOCEPTORS AND NORADRENALINE REUPTAKE IN PITHED NORMOTENSIVE RATS
Authors: CAVERO I. , GOMENI R. , LEFÈVRE‐BORG FRANÇOISE , ROACH A.G. 
Published: July 2012

The cardiovascular effects of intravenous desipramine (0.03 and 0.1 mg/kg), maprotiline (0.5 mg/kg), mianserin (1.0 and 3.0 mg/kg) and phentolamine (0.25 mg/kg) were examined and compared in pithed rats. Several experimental procedures were used in order to distinguish between the effects of the compounds on cardiac presynaptic α‐adrenoceptors and on neuronal noradrenaline reuptake, as inhibition of either mechanism produces an increase of neurotransmitter concentration within the sympathetic synapse and therefore results in a greater end organ response.
Pressor responses elicited by noradrenaline were potentiated by desipramine and maprotiline, reduced by phentolamine and not significantly modified by mianserin. However, all four compounds inhibited the pressor action of tyramine. Furthermore, mianserin reduced the pressor response to adrenaline.
Desipramine, maprotiline and mianserin, but not phentolamine enhanced the positive chronotropic effects of noradrenaline, without affecting those of isoprenaline.
All four compounds abolished the clonidine‐induced inhibition of heart rate responses to short term electrical stimulation of the spinal cord. Moreover, in rats with a persistent tachycardia (induced by continuous stimulation of the thoracic spinal cord) desipramine, maprotiline and mianserin further increased heart rate. This effect was also observed in animals pretreated with phentolamine, administered in order to inhibit cardiac presynaptic α‐adrenoceptors.
In rats with a sustained tachycardia (100 beats/min produced by electrical stimulation of the spinal cord) both mianserin and phentolamine, in contrast to desipramine, shifted the clonidine heart rate dose‐response curve to the right. Phentolamine was about 34 times more potent than mianserin in this respect.
In pithed, reserpine‐treated rats, the pressor responses to clonidine were not significantly modified by desipramine. The dose‐response curves were shifted to the right by phentolamine (0.25 mg/kg) and mianserin (3.0 mg/kg).
These results indicate that mianserin is an antagonist of both cardiac presynaptic and vascular postsynaptic α‐adrenoceptors and also inhibits the neuronal reuptake of noradrenaline.
EVIDENCE FOR BOTH HISTAMINE H1‐ AND H2‐RECEPTORS IN THE GASTRIC VASCULATURE OF THE CAT
Authors: HARVEY CAROL A. , OWEN D.A.A. , SHAW K.D. 
Published: July 2012

Experiments have been done to study the gastric vascular response to histamine given intra‐arterially in the cat.
In experiments utilising pump perfusion of the stomach at constant flow rates, rapid intra‐arterial injections of histamine elicited dose‐dependent vasodilatation. The dose‐response curve to histamine was displaced to the right by mepyramine and further to the right by mepyramine plus cimetidine. Cimetidine alone did not displace the histamine dose‐response curve. This interaction between histamine and histamine antagonists is very similar to the interaction observed in other vascular beds.
Intra‐arterial infusions of histamine also caused vasodilatation with increased gastric blood flow, measured with an electromagnetic flow probe. Mepyramine reduced the immediate increase in blood flow during each infusion, although responses in the later stages of the infusions were unaltered. Cimetidine had no effect on the immediate response but reduced sustained responses to histamine. Treatment with mepyramine and cimetidine was required to abolish histamine responses.
Infusions of 2‐(2‐aminoethyl) pyridine and dimaprit also increased gastric blood flow.
These results indicate the involvement of both H1‐ and H2‐receptors in histamine‐induced gastric vasodilatation. There appears to be a time‐base in the interaction between histamine and vascular histamine receptors; H1‐receptor responses preceding H2‐receptor responses.
ORIGIN OF GUINEA‐PIG PLASMA DOPAMINE β‐HYDROXYLASE
Authors: ARNAIZ J.M. , GARCÍA A.G. , HORGA J.F. , PASCUAL R. , SÁNCHEZ‐GARCÍA P. 
Published: July 2012

Exposure of guinea‐pigs to a CO2‐enriched atmosphere (20% CO2, 25% O2, 55% N2) for 1 to 5 h caused a marked, progressive increase of plasma dopamine β‐hydroxylase (DBH) activity which reached its peak after 2 h of CO2 exposure and then gradually decreased. The increase was abolished by mecamylamine administration before exposure to CO2. Plasma levels of noradrenaline (NA) also increased after CO2 exposure.
Guanethidine administration, before exposure to CO2, abolished the increase of plasma NA but potentiated the increase of circulating DBH. Phenoxybenzamine injection, before exposure to CO2, also potentiated the increase of plasma enzyme activity. In both cases, DBH activity was increased to almost 10 times the basal circulating enzyme levels.
Injection of 6‐hydroxydopamine (6‐OHDA) caused a pronounced decrease of DBH activity in the right atrium, thoracic aorta and spleen; the adrenal enzyme activity was unchanged. Exposure to CO2 of 6‐OHDA‐treated animals still evoked a dramatic increase of plasma DBH activity comparable to that found in control animals.
The increase of plasma DBH activity evoked by exposure to CO2 of adrenalectomized animals was considerably diminished.
These data suggest that in the guinea‐pig, the adrenal is the main source of the increase of circulating DBH activity evoked by exposure of the animals to a CO2‐enriched gas mixture.
ADENOSINE INHIBITION OF γ‐AMINOBUTYRIC ACID RELEASE FROM SLICES OF RAT CEREBRAL CORTEX
Authors: HOLLINS CAROLYN , STONE TREVOR W. 
Published: July 2012

The effect of purine compounds on the potassium‐evoked release of 14C‐labelled γ‐aminobutyric acid (GABA) has been studied in 400 μm slices of rat cerebral cortex in vitro.
Adenosine and adenosine 5′ monophosphate (AMP) inhibited the release of GABA at 10−5 to 10−3 m. Adenosine triphosphate (ATP) produced a significant inhibition of release only at 10−3 m.
Theophylline 10−4 or 10−3 m reduced the inhibitory effect of adenosine, but did not change basal release of GABA.
Dipyridamole 10−5 m itself reduced evoked GABA release, but did not prevent the inhibitory effect of adenosine, implying that adenosine was acting at an extracellularly directed receptor.
Calcium removal or antagonism by verapamil reduced the evoked release of GABA, but adenosine did not produce any further reduction of the calcium‐independent release. This may indicate that the inhibitory effect of adenosine on GABA release results from interference with calcium influx or availability within the terminals.
RELATIONSHIP BETWEEN DURATION OF URETHANE OR PENTOBARBITONE ANAESTHESIA IN MALE AND FEMALE RATS AND ADENOHYPOPHYSEAL RESPONSE TO LUTEINISING HORMONE‐RELEASING HORMONE
Authors: DYER R.G. , MANSFIELD SANDRA 
Published: July 2012

Luteinizing hormone releasing hormone (50 ng/100 g body weight) was injected into male and female rats which had been anaesthetized with either urethane (1.2 g/kg) or pentobarbitone (45 g/kg) for 15, 100 or 240 min and serial blood samples were taken for estimation of plasma luteinizing hormone concentrations.
The rats anaesthetized with urethane tended to show a greater response to the releasing hormone than those given pentobarbitone.
The magnitude of the responses observed in male rats and in female rats anaesthetized with pentobarbitone did not change as the period of anaesthesia prior to injection of releasing hormone was lengthened from 15 min to 4 h. By contrast, in the groups of female rats anaesthetized with urethane the magnitude of the response to luteinizing hormone releasing hormone was related to the length of pretreatment anaesthesia. Thus both dioestrous and pro‐oestrous rats given releasing hormone only 15 min after the onset of urethane anaesthesia had significantly (P < 0.001 and <0.05 respectively) higher concentrations of luteinizing hormone (LH) in the plasma than rats treated with the releasing hormone after 240 min of anaesthesia.
These effects were not due to a differential action of the anaesthetics on the mechanism for clearing LH from the plasma.
MODULATION BY ACETYLCHOLINE OF THE ELECTRICALLY‐EVOKED RELEASE OF [3H]‐ACETYLCHOLINE FROM THE ILEUM OF THE GUINEA‐PIG
Authors: FOSBRAEY P. , JOHNSON E.S. 
Published: July 2012

Acetylcholine (ACh) stores within neurones of the myenteric plexus of the guinea‐pig were labelled with [3H]‐choline and the influence of unlabelled ACh, atropine, or atropine and unlabelled ACh on the electrically‐evoked output of [3H]‐ACh was evaluated.
Electrical transmural stimulation (5 Hz) of the ileum led to an increase in the output of [3H]‐ACh over that released spontaneously. Superfusion with unlabelled ACh (6.8 μm) caused a marked reduction in the release of [3H]‐ACh which was reversed by atropine (3.5 μm). Atropine itself had no effect on the electrically‐evoked [3H]‐ACh.
These experiments provide further evidence for the existence in the guinea‐pig ileum of neuronal muscarinic receptors for ACh subserving an inhibitory role on transmitter release.
ADRENALINE ACTIVATION OF PREJUNCTIONAL β‐ADRENOCEPTORS IN GUINEA‐PIG ATRIA
Authors: MAJEWSKI H. , McCULLOCH M.W. , RAND M.J. , STORY D.F. 
Published: July 2012

Adrenaline in a concentration of 1.0 μm depressed the stimulation‐induced efflux of tritium from the guinea‐pig atria incubated with [3H]‐noradrenaline, whereas adrenaline in a concentration of 0.5 nm significantly enhanced the stimulation‐induced efflux of tritium. This enhancement was blocked by metoprolol (0.1 μm) and thus appears to be mediated by β‐adrenoceptors.
In guinea‐pig atria incubated with unlabelled adrenaline and then with [3H]‐noradrenaline, both catecholamines were released by field stimulation. In such atria metoprolol, practolol, oxprenolol or propranolol decreased the stimulation‐induced efflux of tritium. These effects did not occur if the atria were incubated with unlabelled noradrenaline and then with [3H]‐noradrenaline, suggesting that neuronally released adrenaline activates prejunctional β‐adrenoceptors.
The effect of oxprenolol in decreasing the release of tritium from guinea‐pig atria, incubated with unlabelled adrenaline and then with [3H]‐noradrenaline was greater in the presence of phentolamine. This may reflect the α‐adrenoceptor blocking activity of oxprenolol.
POTENTIATION OF THE EFFECTS OF ADENOSINE ON ISOLATED CARDIAC AND SMOOTH MUSCLE BY DIAZEPAM
Authors: CLANACHAN A.S. , MARSHALL R.J. 
Published: July 2012

Adenosine (10−7 to 3 times 10−4 m) or 2‐chloroadenosine (10−8 to 10−5 m) produced concentration‐dependent inhibition of the responses of the rat isolated vas deferens to electrical field stimulation. In electrically driven (2 Hz) guinea‐pig isolated left atria, adenosine (10−6 to 10−3 m) or 2‐chloroadenosine (10−8 to 10−7 m) produced concentration‐dependent decreases in isometric tension.
Diazepam (10−6 and 10−5 m) had no direct effect per se, but significantly potentiated the inhibitory action of adenosine on both tissues without altering the inhibitory effect of 2‐chloroadenosine.
The adenosine uptake inhibitors, hydroxynitrobenzylthioguanosine (HNBTG, 10−5 m) and dipyridamole (10−5 m) also potentiated the inhibitory actions of adenosine in rat vas deferens, but not those of 2‐chloroadenosine.
Following adenosine uptake inhibition in rat vas deferens by HNBTG (10−5 m), diazepam (10−5 m) failed to produce any significant further potentiation of the inhibitory action of adenosine.
It is concluded that the potentiation of adenosine by diazepam is possibly due to an inhibition of adenosine uptake.