bluuebunny/crossref_metadata_2025_split huggingface dataset:
INTERACTIONS OF (+)‐AMPHETAMINE AND CHLORPROMAZINE ON NEURONES IN THE LOWER BRAIN STEM OF THE RAT
Authors: BOAKES R.J. , BRADLEY P.B. , CANDY J.M. 
Published: July 2012

The ability of chlorpromazine to antagonize the effects of iontophoretic application of (+)‐amphetamine to single neurones in the medulla and lower pons of anaesthetized rats has been studied.
Chlorpromazine, administered systemically or iontophoretically, consistently and specifically antagonized the excitatory actions of (+)‐amphetamine, but not those of noradrenaline on the same neurone.
It is concluded that chlorpromazine reduces the effect of (+)‐amphetamine by a presynaptic mechanism.
(+)‐Amphetamine did not mimic the prolonged inhibitory response of some neurones to noradrenaline but often excited these neurones and chlorpromazine blocked these excitatory responses to (+)‐amphetamine.
THE EFFECTS OF HIGH PRESSURE HELIUM AND NITROGEN ON THE RELEASE OF ACETYLCHOLINE FROM THE GUINEA‐PIG ILEUM
Authors: LITTLE HILARY J. , PATON W.D.M. 
Published: July 2012

The effects of high pressures of helium and of nitrogen on acetylcholine release were tested using the guinea‐pig ileum as a model preparation. A superfusion system was designed in which this tissue could be maintained under physiological conditions in a high pressure chamber.
Helium, at a pressure of 136 atm slightly increased the spontaneous output of acetylcholine but produced no significant changes at 68 atm (136 atm is close to the lethal pressure for small mammals).
The acetylcholine release evoked by electrical stimulation or by 55 mm potassium was not altered by 136 atm of helium. Effects on tetrodotoxin‐treated tissues were not consistent.
Nitrogen, which in contrast to helium possesses general anaesthetic properties, caused considerable increases in spontaneous and in electrically evoked acetylcholine output at pressures which produce anaesthesia. These increases were not changed when helium was used to increase the total pressure to 136 atm, although this reverses the general anaesthetic actions of nitrogen in vivo.
The increases in rate of acetylcholine release produced by nitrogen were observed in tetrodotoxin‐treated tissues and in tissues from reserpine‐treated animals. In a calcium‐free medium the increases were considerably smaller.
The conclusions from these results are that while high pressures of helium caused little or no change in acetylcholine release rates, nitrogen produced large changes, which were not due to effects on axonal conduction. The effect of nitrogen is not apparently related to its general anaesthetic actions. Differences such as these in transmitter release would be likely to contribute to the differing physiological effects of these two gases.
URETHANE AND CONTRACTION OF VASCULAR SMOOTH MUSCLE
Authors: ALTURA BURTON M. , WEINBERG JULIO 
Published: July 2012

In vitro studies were undertaken on rat aortic strips and portal vein segments in order to determine whether or not the anaesthetic, urethane, can exert direct actions on vascular smooth muscle.
Urethane was found to inhibit development of spontaneous mechanical activity. This action took place with a urethane concentration as little as one tenth of that found in anaesthetic plasma concentrations, i.e., 10−3 m.
Urethane (10−3 to 10−1 m) dose‐dependently attenuated contractions induced by adrenaline, angiotensin and KCl. These inhibitory actions were observed with urethane added either before or after the induced contractions.
Ca2+‐induced contractions of K+‐depolarized aortae and portal veins were also attenuated, dose‐dependently, by urethane.
All of these inhibitory effects were completely, and almost immediately, reversed upon washing out the anaesthetic from the organ baths.
A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects induced by urethane.
These data suggest that plasma concentrations of urethane commonly associated with induction of surgical anaesthesia can induce, directly, relaxation of vascular muscle.
ATTENUATION BY BRADYKININ OF ADRENERGICALLY‐INDUCED VASOCONSTRICTION IN THE ISOLATED PERFUSED KIDNEY OF THE RABBIT: RELATIONSHIP TO PROSTAGLANDIN SYNTHESIS
Authors: MALIK K.U. , NASJLETTI A. 
Published: July 2012

In the isolated kidney of the rabbit perfused with oxygenated Tyrode solution, we studied the effect of bradykinin on the vasoconstriction evoked by sympathetic nerve stimulation (3 Hz, 1 ms) and by injections of noradrenaline (50 to 75 ng) in the presence and in the absence of indomethacin (1 μg/ml), an inhibitor of prostaglandin biosynthesis. Prostaglandin E(PGE)‐like material in the renal effluent was measured by bioassay after extraction with organic solvents and separation by thin layer chromatography.
Bradykinin in concentrations of 10 to 100 ng/ml reduced the vasoconstrictor response to sympathetic nerve stimulation and to injected noradrenaline. Also, the peptide (1 to 10 ng/ml) increased the basal release of PGE‐like material and the release induced by sympathetic nerve stimulation.
Indomethacin, 1 μg/ml, diminished the inhibitory effect of bradykinin on the vasoconstrictor response to nerve stimulation, minimized the reduction of the noradrenaline‐induced vasoconstriction caused by bradykinin (100 ng/ml), and abolished the release of PGE‐like material.
This study indicates that bradykinin reduces the renal vascular reactivity to adrenergic stimuli and suggests that part of the action of the kinin at the vascular adrenergic neuroeffector junction in the rabbit kidney depends upon the biosynthesis of renal prostaglandins.
PRESYNAPTIC α‐ADRENOCEPTOR BLOCKING PROPERTIES AMONG TRI‐ AND TETRA‐CYCLIC ANTIDEPRESSANT DRUGS
Authors: HARPER BARBARA , HUGHES I.E. 
Published: July 2012

The effect of various antidepressants (5 × 10−8 to 2 × 10−5 m) on the resting overflow of tritium, on the evoked overflow and the contractile response to electrical stimulation (2.5 Hz, 2.0 ms) has been determined in mouse vas deferens previously incubated with [3H]‐(–)‐noradrenaline.
Mianserin and ORG GC 94 produced a concentration‐dependent increase of more than two fold in the electrically evoked overflow and the contractile response and, at the highest concentration, slightly increased resting release. These effects were largely unchanged in the presence of a concentration of cocaine effective in blocking noradrenaline uptake (1.1 × 10−5 m).
The ability of phentolamine (1 × 10−5 m) to increase both the evoked overflow of tritium and the contractile response was greatly reduced when these parameters were already elevated by the presence of mianserin or ORG GC 94.
The inhibitory effect of exogenous (–)‐noradrenaline on evoked overflow was greatly reduced in the presence of mianserin or ORG GC 94 (4 × 10−6 m).
The inhibitory effect of clonidine on the twitch response of the mouse vas deferens was antagonized by mianserin and ORG GC 94 in a competitive manner (pA2 values 7.3 and 7.1 respectively).
Maprotiline, desipramine and nortriptyline (> 3 × 10−6 m) produced a parallel fall in both evoked tritium overflow and in the contractile response and increased the resting overflow at higher concentrations. These effects were largely unchanged in the presence of cocaine (1.1 × 10−5 m).
Doxepin, imipramine and iprindole all increased resting overflow at high concentrations (2 × 10−5 m) but produced only small changes in evoked overflow and in the contractile response at lower concentrations.
It is concluded that mianserin and ORG GC 94 produce a blockade of presynaptic α‐adrenoceptors which could contribute to an antidepressant effect but that this type of action is not common to all antidepressants.
A PHARMACOLOGICAL ANALYSIS OF THE CONTRACTILE ACTION OF HISTAMINE UPON THE ILEAL REGION OF THE ISOLATED, BLOOD‐PERFUSED SMALL INTESTINE OF THE RAT
Authors: SAKAI K. 
Published: July 2012

The mode of action of histamine was investigated on the rat isolated small intestine perfused at a fixed flow rate through the superior mesenteric artery with blood from the carotid artery of a heparinized donor rat. Compounds were closely injected into the superior mesenteric artery.
Increasing doses (1 to 100 μg) of histamine caused a monophasic fast contraction of the ileum.
The fast contraction was abolished by tetrodotoxin, hexamethonium, morphine or mepyramine, but was not prevented by atropine.
The present study indicates that histamine produces the fast contraction of the ileum by primarily acting on the myenteric nerve plexus involving cholinergic interneurones.
MORPHINE DEPRESSION AND TOLERANCE OF NERVE‐INDUCED PAROTID SECRETION
Authors: BOWEN S.R. , CARPENTER F.G. 
Published: July 2012

The nerve‐induced secretion produced by the rat parotid gland is proportional to the frequency of stimulation. Morphine decreased the flow rate during stimulation at 2.5 and 5 Hz, but not at 20 Hz. This frequency‐dependent action of morphine was partially reversed by naloxone.
The secretion produced by the rat parotid gland during an intravenous infusion of acetylcholine was not diminished by morphine. Therefore, the action of morphine on nerve‐induced secretion is most probably on the motor nerve terminals, which release acetylcholine.
Animals that had been implanted with morphine base pellets tolerated 4 times as much morphine as controls; after 6 days the minute ventilation was less depressed by graded doses of morphine than non‐implanted controls.
Nerve‐induced secretion in morphine‐implanted animals was less depressed by morphine than control animals 6 and 24 h after the pellets were removed. The flow rates in the 6 h group treated with morphine were greater after naloxone than control (precipitated withdrawal) but at 24 h when withdrawal symptoms were no longer evident, naloxone produced only a slight reversal.
EFFECTS OF NORADRENALINE AND CARBACHOL ON TEMPERATURE REGULATION OF RATS
Authors: POOLE S. , STEPHENSON J.D. 
Published: July 2012

Noradrenaline (0.2 to 20 ug) and carbachol (0.1 to 1 ug) injected into the preoptic/anterior hypothalamic area, evoked dose‐dependent falls in core temperature at all sites tested, followed in most experiments by delayed increases that were not dose‐related. Muscarine (0.1 to 10 ug) produced effects similar to those evoked by carbachol.
These falls in core temperature were associated with increases in tail temperature, locomotor activity and C02 elimination (a measure of metabolic rate).
The temperature responses to noradrenaline (10 ug) and to carbachol (1 ug) were antagonized by intrahypothalamic injections of phentolamine (10 ug) and atropine (1 ug), respectively.
Analysis of the temperature responses and their respective latencies indicates that carbachol‐induced hypothermia was mediated by cholinoceptors in the anterior hypothalamus, whereas hypothermia after noradrenaline was mediated by adrenoceptors throughout the preoptic/anterior hypothalamic area.
Vasodilatation of the tail blood vessels contributed significantly to the hypothermia evoked by carbachol, and to that evoked by injections of noradrenaline into the anterior hypothalamus.
Hypothermia induced by noradrenaline injection into the preoptic area, was mediated by effector mechanisms additional to non‐evaporative heat loss.
EFFECTS OF 2,4‐DINITROPHENOL AMYLOBARBITONE AND CERTAIN OTHER DRUGS ON THE RATE OF OXYGEN CONSUMPTION AND FORCE OF CONTRACTION OF ISOLATED CURARIZED DIAPHRAGM MUSCLE OF THE RAT
Authors: BERESFORD ROSEMARY , BILLS G.N.B. , FASTIER F.N. , MILNE R.J. 
Published: July 2012

A technique has been developed for studying over periods of 10 min or longer the effects of drugs on both the force of electrically‐induced contractions and the oxygen consumption of an isolated, curarized, mammalian, skeletal muscle preparation.
The resting oxygen consumption of the muscle was increased substantially by 2,4‐dinitrophenol in concentrations (0.02 mm and higher) that eventually produced contracture. Two other uncoupling agents, 4,6‐dinitro‐o‐cresol and carbonylcyanide‐p‐trifluoromethoxyphenylhydrazone, behaved similarly.
The oxygen consumption over 10 min of the stimulated muscle was also increased by 2,4‐dinitrophenol (0.05 mm), although the strength of the ‘maximal’ contractions was lessened.
Amylobarbitone increased the strength of contraction at a concentration (0.2 mm) that did not affect oxygen consumption significantly. Amylobarbitone and pentobarbitone also increased it at a concentration (1 mm) that depressed oxygen consumption. They decreased both strength of contraction and oxygen consumption at a concentration of 5 mm. Phenobarbitone had a weaker action.
S‐w‐decyl‐thiouronium increased oxygen consumption when given at a concentration (1 mm) that diminished strength of contraction and eventually produced contracture of the muscle.
Both S‐methyl‐thiouronium (1 mm) and 4‐aminopyridine (0.1 mm and 0.5 mm) increased strength of contraction without increasing oxygen consumption. Neither strength of contraction nor oxygen uptake was affected by ouabain (up to 0.01 mm) or by phenformin (0.1 mm).
It is concluded that the response to 2,4‐dinitrophenol is due mainly, if not wholly, to its known ability to uncouple oxidative phosphorylation; that the response to the barbiturates is due to a combination of a known metabolic action (viz., blocking of the respiratory chain) and a stimulant action on muscle; and the response to S‐w‐decyl‐thiouronium to a disruptive action on cell membranes. The disproportionate actions of 4‐aminopyridine and S‐methyl‐thiouronium on strength of contraction relative to oxygen consumption are also attributed to a non‐metabolic action.
UTILIZATION OF ADENOSINE TRIPHOSPHATE IN RAT MAST CELLS DURING HISTAMINE RELEASE INDUCED BY THE IONOPHORE A23187
Authors: JOHANSEN TORBEN 
Published: July 2012

The rôle of endogenous adenosine triphosphate (ATP) in histamine release from rat mast cells induced by the ionophore A23187 in vitro has been studied.
The amount of histamine released by calcium from rat mast cells primed with the ionophore A23187 was dependent on the ATP content of the mast cells.
In aerobic experiments a drastic reduction in mast cell ATP content was found during the time when histamine release induced by A23187 takes place.
Anaerobic experiments were performed with metabolic inhibitors (antimycin A, oligomycin, and carbonyl cyanide p‐trifluorometroxyphenylhydrazone), which are known to block the energy‐dependent calcium uptake by isolated mitochondria. The mast cell ATP content was reduced during A23187‐induced histamine release under anaerobic conditions in the presence of glucose. This indicates an increased utilization of ATP during the release process.
The observations are consistent with the view that energy requiring processes are involved in ionophore‐induced histamine release from rat mast cells although part of the ATP reduction in the aerobic experiments may be due to an uncoupling effect of calcium on the oxidative phosphorylation.
THE EFFECTS OF OPIATE RECEPTOR AGONISTS AND ANTAGONISTS ON THE STRESS‐INDUCED SECRETION OF CORTICOSTERONE IN MICE
Authors: GIBSON A. , GINSBURG M. , HALL M. , HART S.L. 
Published: July 2012

Intraperitoneal administration of normorphine, morphine or naloxone or exposure to ethervapour for 1 miri, elevated plasma corticosteroid concentrations in mice.
Injection of saline or exposure to ether vapour rendered mice less sensitive to a subsequent exposure to ether vapour 15 min later.
Treatment with normorphine (50 mg/kg) potentiated the corticosteroid response to ether stress whilst pentazocine (20 mg/kg), naltrexone (10 mg/kg), morphine (24 mg/kg), levorphanol (20 mg/kg) and naloxone (50 mg/kg) prevented the stress‐induced elevation of plasma corticosteroids.
Both naloxone and morphine inhibited the potentiation by normorphine of the response to ether, the dose of naloxone required being higher than that for inhibition of normorphine analgesia.
It is concluded that endogenous opioid peptides may be involved in the control of the response to ether stress in mice.
THE METABOLISM OF 5‐HYDROXYTRYPTAMINE AND β‐PHENYL‐ETHYLAMINE IN PERFUSED RAT LUNG AND IN VITRO
Authors: BAKHLE Y.S. , YOUDIM M.B.H. 
Published: July 2012

Metabolism of 5‐hydroxytryptamine (5‐HT) and βt‐phenylethylamine (PHE) by monoamine oxidase (MAO) was investigated in rat isolated lungs and in mitochondrial preparations from rat lung.
In perfused lungs 5‐HT metabolism had an apparent Km of 2 μm and PHE metabolism a Km of 54 μm, whereas in vitro the Km values were 330 μm and 28 μm respectively.
In vitro, MAO activity had substrate and inhibitor specificities compatible with the presence of A and B types of MAO.
In perfused lung, metabolism of 5‐HT but not that of PHE was inhibited by desmethylimipramine.
These results show that PHE metabolism in perfused lung, unlike that of other metabolized amines, is not limited by transport and the transport process for PHE is unlike that of 5‐HT or noradrenaline.
These results also show that the kinetic parameters obtained for MAO activity in vitro do not generally apply to the isolated lung where transport of substrate can be the deciding factor. This discrepancy emphasizes that the enzymic properties of the whole organ cannot reliably be deduced from its enzymic content.
THE INTERACTION BETWEEN INDOMETHACIN AND CONTRACTILE AGENTS ON HUMAN ISOLATED AIRWAY MUSCLE
Authors: BRINK CHARLES , GRIMAUD CHARLES , GUILLOT CHANTAL , OREHEK JEAN 
Published: July 2012

Concentration‐effect curves to acetylcholine and histamine were produced in fresh human bronchial muscle (2 to 4 h after removal from the patients) and in preparations previously stored at 4°C for 12 h.
Sensitivities of fresh human airway muscle preparations to acetylcholine (pD2 value, 5.89 ± 0.03); n = 4) and histamine (pD2 value, 5.41 ± 0.03; n = 13) were similar. There was no significant difference in the sensitivities of stored preparations (acetylcholine: pD2 value, 5.70 ± 0.06; n = 23 and histamine: pD2 value, 5.44 ± 0.07; n = 16) when compared to the fresh preparations.
Indomethacin did not significantly change the basal tone in preparations of either fresh or stored human airway muscle.
A low concentration of indomethacin (0.17 μm) significantly reduced responsiveness and sensitivity to histamine in stored bronchi but not in fresh bronchi. The acetylcholine concentration‐effect curves were unaltered by exposure to this concentration of indomethacin in either fresh or stored tissues. High concentrations (1.7 μm and 17 μm) depressed the maximal responsiveness of the bronchi to both agonists.
These results suggest indirectly that the regulatory role of prostaglandins in human airway muscle may be different from that in other species.
EFFECTS OF ACETYLCHOLINE AND SODIUM CYANIDE ON CAT CAROTID BARORECEPTORS
Authors: McQUEEN D.S. 
Published: July 2012

The effects of intracarotid (i.a.) injections of acetylcholine (ACh) and sodium cyanide (NaCN) on baroreceptor activity recorded from the sinus nerve have been investigated in cats anaesthetized with pentobarbitone.
Two types of baroreceptor unit were recorded. The predominant type discharged at least 3 to 4 spikes per pulse wave at normal BP; they are referred to as ‘polyspike’ units and may have been associated with A fibres. The other type discharged a maximum of 1 to 3 spikes per pulse wave, even at high BP; they are referred to as ‘few‐spike’ units and may have been from C fibres.
NaCN had no direct effect on either type of baroreceptor unit, even when injected in high doses (2.04 to 5.1 μmol i.a.) which cause maximal chemoreceptor stimulation, and it is concluded that as far as the cat's carotid baroreceptors and chemoreceptors are concerned, NaCN is a specific chemoreceptor stimulant.
ACh had no direct effect on polyspike baroreceptor units unless very high doses (1.83 μmol i.a.) were injected, when there was occasionally a transient slight increase in discharge. This effect appeared to be secondary to muscle contraction caused by ACh since it was not seen when an adequate neuromuscular‐blocking dose of gallamine had been administered.
ACh stimulated the few‐spike type of baroreceptor unit, an effect which was dose‐related and lasted for up to 3 s; the threshold dose for baroreceptor stimulation was higher than that needed to excite chemoreceptor units. The increased discharge also occurred during experiments in which gallamine had been administered. Only five of these units were recorded during the investigation, despite an intensive search for them.
There was a delayed increase in baroreceptor sensitivity following the administration of ACh in doses (37 to 366 nmol i.a.) which had no immediate direct effect on polyspike baroreceptor discharge. The effect was evidently not secondary to changes in sympathetic nerve activity to the sinus region since it was observed during an experiment in which the ganglioglomerular nerves had been cut. Whether the increased sensitivity resulted from direct or indirect actions of ACh remains to be determined.
It is concluded that low doses of ACh or other drugs with nicotinic properties are unlikely to evoke baroreceptor reflexes on intracarotid injection, although they may cause delayed changes in baroreceptor sensitivity. Higher doses of ACh do not directly affect baroreceptor polyspike (A fibre) units, but transient baroreflex changes might result from stimulation of baroreceptor few‐spike (C fibre) units. It is most unlikely that NaCN has any direct effect on baroreceptor reflex activity when injected into the carotid artery in doses used to elicit chemoreceptor reflexes.
MORPHINE AND SUPRASPINAL INHIBITION OF SPINAL NEURONES: EVIDENCE THAT MORPHÌNE DECREASES TONIC DESCENDING INHIBITION IN THE ANAESTHETIZED CAT
Authors: DUGGAN A.W. , GRIERSMITH B.T. , NORTH R.A. 
Published: July 2012

A study was made in cats anaesthetized with barbiturate or α‐chloralose, of the excitation of dorsal horn neurones by impulses in unmyelinated (C) primary afferent fibres of the tibial nerve.
Block of conduction in the first lumbar segment by cooling produced large increases in the number of action potentials evoked by C fibre afferents in neurones of more caudal segments.
Morphine (0.3 to 1.0 mg/kg) reduced the excitation of neurones by C fibre afferents and also reduced the increase produced by blocking conduction in the spinal cord. Naloxone (0.1 to 0.3 mg/kg) reversed these effects of morphine.
This decrease in descending inhibition supports findings in the decerebrate cat but gives no support to the hypothesis that an important component of morphine analgesia is an activation of descending inhibitory pathways.