bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of muscarine given into the brain of fowls
Authors: MARLEY E. , SELLER T. J. 
Published: July 2012

Summary
The effects of muscarine, given intraventricularly, in adult conscious fowls (Gallus domesticus) or microinfused into various brain regions of conscious young chicks, were tested on behaviour, electrocortical activity and respiratory rate. Its effects given intraventricularly or intravenously to anaesthetized fowls were also examined.
After intraventricular injection, muscarine elicited immediate behavioural and electrocortical arousal; body temperature was unaffected. After a delay of 30–40 min, tachypnoea developed together with postural changes which included partial abduction of the wings away from the trunk, the back and tail becoming horizontal. These effects were prevented by intravenous or intraperitoneal atropine or hyoscine, but not by pempidine or methylatropine, and were potentiated by physostigmine. Hyoscine given intraventricularly or intravenously did not affect electrocortical activity.
Intraventricular muscarine given to anaesthetized adult fowls produced brief apnoea. On return of respiration, amplitude of respiratory excursion was diminished for about 5 min; tachypnoea did not develop. Blood pressure also rose briefly. With larger doses of intraventricular muscarine, large amplitude electromyographic potentials developed in the dorsal neck muscles followed later by side‐to‐side neck movements.
Muscarine given intravenously to anaesthetized adult fowls, raised blood pressure and perfusion pressure in a perfused hind limb, an effect most likely due to secretion of adrenal medullary catecholamines; these pressor effects were prevented by pempidine and phenoxybenzamine. Given directly to the perfused hind limb, muscarine lowered perfusion pressure.
In young chicks, muscarine microinfused into the diencephalon or myelencephalon elicited intense bilateral electrocortical alerting associated with periods of alternating violent motor activity and quiescence. Microinfusion of muscarine into the telencephalon induced ipsilateral electrocortical desynchronization without affecting behaviour. These effects of muscarine were prevented by intravenous, intraperitoneal or intracerebral hyoscine, but once its effects were established could be antagonized only with difficulty; pempidine did not prevent these effects. Microinfusions of muscarine into the brain did not affect posture, respiration or temperature.
Mechanisms by which human blood platelets accumulate glycine, gaba and amino acid precursors of putative neurotransmitters
Authors: BOULLIN D. J. , GREEN A. R. 
Published: July 2012

Summary
. We have examined the accumulation by human blood platelets of amino acids that are believed to be involved in neurohumoral transmission in the central nervous system.
. Platelets were incubated in Ca++‐free Krebs solution at 37° C with radioactive amino acids for various times and then the platelets were analysed for the radioactive substance and its metabolites.
. l‐Phenylalanine, l‐DOPA, l‐tryptophan and l‐tyrosine were rapidly accumulated, the equilibrium tissue/medium concentration ratio (Ci/Co) being greater than 10: 1 when the concentration of amino acid in the medium was 10−7m or lower. Glycine and γ‐aminobutyric acid (GABA) accumulation was less, Ci/Co being lower than 3: 1 when Co was 10−7m.
. Uptake of l‐phenylalanine, l‐DOPA and l‐tryptophan were all decreased or abolished by incubation at 4° C, or with metabolic inhibitors or by disruption of the platelet membrane prior to incubation, while l‐tyrosine accumulation was not affected.
. It is considered that l‐phenylalanine, l‐DOPA and l‐tryptophan are accumulated by saturable, energy‐dependent processes; that glycine and GABA diffuse into the platelet, and l‐tyrosine accumulates as a result of diffusion and intracellular binding.
. None of the amino acids examined showed any significant metabolism during a 20 min incubation. However, some evidence for tyrosine binding to soluble protein was obtained.
. Results are compared to reports of accumulation of these amino acids by the central nervous system.
The 5‐hydroxytryptamine‐like actions of 5,6‐dihydroxytryptamine
Authors: BARZAGHI F. , BAUMGARTNER H. R. , CARRUBA M. , MANTEGAZZA P. , PLETSCHER A. 
Published: July 2012

Summary
. With isolated preparations of rat stomach fundus as well as of duodenum and ileum of rats and guinea‐pigs, 5,6‐dihydroxytryptamine and 5,6‐diacetoxytryptamine caused a contraction which was antagonized by methysergide and lysergic acid diethylamide (LSD), but not by atropine. Pretreatment of the animals with reserpine did not decrease the effect of the two indoleamines on the isolated ileum and duodenum.
. In anaesthetized guinea‐pigs, 5,6‐dihydroxytryptamine and its diacetyl derivative caused bronchoconstriction which was antagonized by methysergide, but not modified by pretreating the animals with reserpine.
. In anaesthetized cats, 5,6‐dihydroxytryptamine had, in general, a hypotensive effect which was reversed by hexamethonium.
. 5,6‐Dihydroxytryptamine also caused aggregation of isolated rabbit and human platelets and inhibited the platelet aggregation induced by 5‐hydroxytryptamine (5‐HT) plus adrenaline.
. The pattern of action of 5,6‐dihydroxytryptamine and 5,6‐diacetoxytryptamine was qualitatively the same as that of 5‐HT, but the potency of the compounds decreased in the order 5‐HT, 5,6‐dihydroxytryptamine, 5,6‐diacetoxytryptamine both in vitro and in vivo.
. It is concluded that 5,6‐dihydroxytryptamine and its diacetyl derivative stimulate postsynaptic 5‐HT receptors, but that their effect is weaker than that of 5‐HT.
Tolerance to the hypothermic effects of Δ9‐tetrahydrocannabinol as a function of age in the chicken
Authors: ABEL E. L. , McMILLAN D. E. , HARRIS L. S. 
Published: July 2012

Summary
(—)‐Δ9‐Tetrahydrocannabinol was administered to chicks (Gallus domesticus) of various ages and body temperature and tolerance to the hypothermic effects of the drug were examined as a function of age.
The hypothermic effects were found to be greater in neonatal than older animals and likewise tolerance took longer to develop in younger chicks.
The rate of tolerance development, however, could be increased in the neonate by preadministration of a high dose of the drug.
The effects of anti‐Parkinson drugs on cortical neurones
Authors: CLARKE G. , DAVIES J. 
Published: July 2012

Summary
The effects of a potential anti‐Parkinson drug, benapryzine, have been compared with those of benzhexol, atropine and procaine on the excitatory responses induced by acetylcholine and l‐glutamate on feline cortical neurones using the microiontophoretic technique.
All the drugs tested reduced the excitatory responses evoked by acetylcholine and l‐glutamate. However, benapryzine, benzhexol and procaine more effectively reduced the excitatory responses to l‐glutamate than those to acetylcholine whereas atropine was more effective against acetylcholine‐induced excitation.
In the presence of procaine the amplitude of the extracellular spikes was decreased. This effect was also observed during applications of benapryzine and benzhexol.
Tests on the isolated frog sciatic nerve indicated that benapryzine and benzhexol had local anaesthetic actions respectively greater than and equivalent to those of procaine.
It was concluded that the effects of benapryzine and benzhexol on cortical neurones were probably related to their local anaesthetic properties. The possibility that a local anaesthetic action may account for the effects of these drugs and of many other commonly used anti‐Parkinson drugs in Parkinson's disease is discussed.
Antinociceptive action of bradykinin and related kinins of larger molecular weights by the intraventricular route
Authors: RIBEIRO S. A. , SILVA M. ROCHA E 
Published: July 2012

Summary
It was shown previously that bradykinin (Bk) when given intraventricularly increases the threshold of electrical stimulation of dental pulp in the rabbit.
Bradykinin derivatives with increasing molecular weights (lysyl‐Bk (L‐Bk), methionyl‐lysyl‐Bk (ML‐Bk) and glycyl‐arginyl‐methionyl‐lysyl‐Bk (GAML‐Bk)) were found to produce effects of decreasing intensity on the threshold of electrical stimulation according to the following scale: Bk (1·00)>L‐Bk (0·28)>ML‐Bk (0·060)>GAML‐Bk (0·047).
The four peptides had similar relative activities on the guinea‐pig ileum but an inverse relationship in their effects on vascular permeability and rat blood pressure.
The discrimination index, increase in vascular permeability/antinociceptive effect rose to values of the order of 170 to 550, taking Bk as the reference peptide (potency = 1·00).
We conclude that the increase in threshold of electrical stimulation could not be due to an increase in vascular permeability or decrease of blood pressure.
Effects of Naja nivea venom on nerve, cardiac and skeletal muscle activity of the frog
Authors: LOOTS J. M. , MEIJ H. S. , MEYER B. J. 
Published: July 2012

Summary
The effects of 1 mg/ml whole Naja nivea (Cape cobra) venom, and of three different toxins isolated from it, on spinal reflex excitability and cardiac and skeletal muscle activity of the frog (Xenopus laevis), were studied. Isolated spinal cords, sciatic nerve‐gastrocnemius muscle units and isolated heart preparations were used.
Synaptic efficiency and/or motoneurone excitability ceased totally and irreversibly after the application of whole venom within 18·5 minutes. The application of α toxin caused polysynaptic reactivation of the motoneurones after the monosynaptic response elicited by electrical stimulation, i.e. it had an excitatory effect, which was retained after washing off the toxin. The effect of β toxin resembled that of α toxin, except that the effect was lost after the toxin was washed off. The δ toxin abolished all nervous reactivity irreversibly and was found to be 2·64 times more effective in this respect than whole venom.
Responses of the gastrocnemius muscle to electrical stimulation of its motor nerve ceased 10 to 20 min after application of the venom. The muscle usually still responded slightly to direct stimulation for a few minutes. The effect was irreversible. The venom did not only block neuromuscular transmission, but also affected the muscle fibre itself. Nerve conductivity was relatively resistant to the venom; α and β toxins produced similar results but were less effective.
The application of whole venom (1 mg/ml) to the isolated heart resulted in complete spasm of the ventricle within 3 to 8 minutes. The atria continued contracting long after the ventricle ceased. When the venom was washed off, contractions of the atria were restored, while the ventricle remained irreversibly in a state of spasm. The α, β and 8 toxins weakened the contractions of the ventricle, but did not produce spasm. The effect on the ventricle was reversible. Contractions of the atria remained apparently unaltered.
Adrenergic control of tendon jerk reflexes in man
Authors: PHILLIPS SUSAN J. , RICHENS A. , SHAND D. G. 
Published: July 2012

Summary
Tendon jerk responses and H reflexes were recorded from conscious human volunteers before and after intravenous injection of methylamphetamine, thymoxamine and propranolol, and during intravenous infusion of noradrenaline.
Methylamphetamine produced a significant increase in the amplitude of the tendon jerk, whereas noradrenaline had no effect in doses which caused a greater pressor response than methylamphetamine.
Thymoxamine produced a dose‐related reduction in the tendon jerk.
Propranolol had no significant effect on the jerk.
None of these drugs significantly affected the H reflex.
It is suggested that central adrenoceptors, possibly α in type, exist in man, and that stimulation of these receptors facilitates tendon jerk reflexes by an action on the fusimotor system.
Morphine analgesia, tolerance and physical dependence in the adrenalectomized rat
Authors: WEI E. 
Published: July 2012

Summary
Adrenalectomy reduced the median antinociceptive dose (AD50) of morphine in male Sprague‐Dawley rats. The antinociceptive effect was assessed by the tail‐flick method of D'Amour & Smith (1941).
Tolerance to the antinociceptive effect of morphine developed in adrenalectomized and sham‐operated rats after chronic exposure to morphine. Development of tolerance did not significantly alter the increased sensitivity of adrenalectomized rats to the antinociceptive effect of morphine.
Adrenal weights were not increased in rats rendered physically dependent on morphine by subcutaneous implantation of a morphine pellet. Withdrawal, induced by intraperitoneal injection of naloxone hydrochloride, 4 mg/kg, or by removal of the implanted pellet, resulted in a rapid increase in adrenal weight.
In morphine‐dependent animals, the incidence of abstinence signs and body weight loss during precipitated withdrawal did not appear to be significantly influenced by adrenalectomy or by corticosterone‐pretreatment.
Mechanism of histamine‐induced antidiuretic response
Authors: BHARGAVA K. P. , KULSHRESTHA V. K. , SANTHAKUMARI G. , SRIVASTAVA Y. P. 
Published: July 2012

Summary
In dogs anaesthetized with α‐chloralose, intracerebroventricular (i.c.v.) injection of histamine induced antidiuresis and increase in jugular vein blood antidiuretic hormone (ADH) level but no change in urinary electrolytes. The mechanism of the histamine‐induced antidiuretic response was analysed by the use of pharmacological agents.
Histamine (i.c.v.) in 1–20 μg doses produced a variable effect on urine outflow as well as on the blood ADH concentration; however, higher doses (25–500 μg) of histamine elicited a dose‐dependent antidiuretic response with concomitant rise in blood ADH titre.
Repeated administration of high doses of i.c.v. histamine (400 μg) elicited a diminishing antidiuretic response which was not observable after the fourth dose, thus exhibiting tachyphylaxis. The antidiuretic response to histamine could be restored by central administration of noradrenaline (500 μg).
Central pretreatment with mepyramine (5 mg) prevented the histamine‐induced antidiuresis. Atropine (2 mg i.c.v.) was ineffective in blocking the antidiuretic effect of histamine. A diuretic response to histamine (400 μg i.c.v.) was obtained in phenoxybenzamine (i.c.v.) pretreated animals; this response could be blocked by i.c.v. injection of propranolol. Tetrabenazine pretreatment prevented the antidiuretic response to histamine.
The results of the study lead us to conclude that histamine releases central catecholamines which activate the central adrenergic mechanism for the release of antidiuretic hormone.
Release of noradrenaline from the cat spleen by sodium deprivation
Authors: GARCIA A. G. , KIRPEKAR S. M. 
Published: July 2012

Summary
The endogenous noradrenaline content of cat spleen slices was markedly reduced when the slices were incubated at 37° C in a medium in which sodium was replaced by sucrose, lithium, choline or potassium. Depletion of tissue noradrenaline was accounted for by its release into the incubating medium. At an external sodium concentration of 20 mm, about 50% depletion was obtained in 2 hours.
The enhanced release induced by sodium deprivation occurred in the absence of calcium, with or without ethyleneglycol‐bis (β‐aminoethyl ether) N,N' tetraacetic acid. Manganese potentiated release, while magnesium was without effect.
Ouabain caused a dose‐dependent release of noradrenaline which was partially calcium‐dependent. Removal of potassium from the incubation medium caused some release, which was potentiated in 25 mm sodium Krebs solution or by ouabain.
At 4° C, the release did not occur in sodium‐free medium.
Dinitrophenol did not affect the loss of noradrenaline caused by sodium withdrawal. Iodoacetic acid and N‐ethylmaleimide caused a time‐dependent depletion of noradrenaline. Tetracaine caused release and partly opposed the release caused by sodium deprivation. Tetrodotoxin had no effect. Guanethidine, but not phenoxybenzamine, released noradrenaline and potentiated the release induced by sodium withdrawal.
The rate of release of 3H‐noradrenaline from reserpine‐treated spleen slices was not altered by sodium withdrawal.
Uptake‐retention of 3H‐noradrenaline in slices depleted of their endogenous noradrenaline content by sodium deprivation was about 60% of the control slices. This was effectively blocked by cocaine. Release of 3H‐noradrenaline evoked by high potassium from both control and treated slices was calcium‐dependent.
It is suggested that sodium‐potassium‐activated ATPase maintains the integrity of the axonal membrane, and any procedure which depresses the activity of the enzyme or the sodium‐potassium pump would cause transmitter release by causing temporary disturbance in the membrane. Evidence is presented to suggest that vesicles depleted of their endogenous noradrenaline content by sodium deprivation are re‐used for the storage and release of transmitter.
Effects of oxyfedrine on isolated portal vein and other smooth muscles
Authors: MACKENZIE J. E. , PARRATT J. R. 
Published: July 2012

Summary
Oxyfedrine (001–1·0 μg/ml), inhibited spontaneous myogenic activity in rat isolated portal vein and carbachol‐induced contractions of rat isolated uterus, and relaxed the rabbit duodenum and the guinea‐pig tracheal chain preparation. These actions were prevented by the β‐adrenoceptor blocking drug alprenolol. Oxyfedrine was a relatively weak β‐adrenoceptor stimulant (10–100 times less active than isoprenaline) but its actions were more prolonged.
In the same concentrations, oxyfedrine reduced or prevented the inhibition of myogenic activity of the rat portal vein induced by isoprenaline and by repeated doses of oxyfedrine itself, acting as a partial agonist at β‐adrenoceptor sites.
Oxyfedrine, 1–12 μg/ml increased myogenic activity in the rat portal vein. This effect was not due to direct or indirect stimulation of α‐adrenoceptors (because it was unaffected by phentolamine) or to potentiation of acetylcholine or 5‐hydroxytryptamine.
Oxyfedrine (>20 μg/ml) inhibited spontaneous myogenic activity in the portal vein and relaxed the saphenous vein contracted with noradrenaline. This spasmolytic effect of the drug was not due to β‐adrenoceptor stimulation or to inhibition of phosphodiesterase since it was unaffected by alprenolol and by concentrations of imidazole which antagonized the effects of the active phosphodiesterase inhibitor, papaverine. In the portal vein this effect of oxyfedrine was similar to that of the calcium inhibitor iproveratril; some of the effects of oxyfedrine on venous smooth muscle may be mediated through effects on calcium transport.
A method for comparing the potencies of γ‐aminobutyric acid antagonists on single cortical neurones using micro‐iontophoretic techniques
Authors: HILL R. G. , SIMMONDS M. A. 
Published: July 2012

Summary
By the use of micro‐iontophoretic techniques, quantitative estimates of the depressant effect of γ‐aminobutyric acid (GABA) have been obtained from single neurones in the middle suprasylvian gyrus of cat cerebral cortex.
The progressive reduction in firing rate of the neurone during each micro‐iontophoretic application of GABA was followed until inhibition was complete. The resultant time‐response curves represented cumulative concentration‐response relationships which could be characterized by measuring the time taken to achieve 50% inhibition (T50) of neuronal firing.
The time‐response curves for GABA could be displaced along the time axis by micro‐iontophoretic application of picrotoxin, bicuculline or strychnine. A displaced curve was more nearly parallel to the control curve when responses were plotted against linear rather than log time.
Picrotoxin usually increased T50 values for GABA, bicuculline could both increase and decrease them and strychnine usually decreased them.
When displacements of GABA response curves were expressed as difference between T50 (test—control)/T50 (control), the values obtained were minimally influenced by the size of the current applying GABA and were unaffected by changes in the retaining current passed through the GABA barrel between applications.
The use of this method to compare the micro‐iontophoretic potencies of different GABA antagonists is discussed.
Renin release from the ischaemic kidney
Authors: LONG JOAN S. , SEVERS W. B. 
Published: July 2012

Summary
We have confirmed that spinal section, and also pithing, inhibits the pressor response associated with the release of renin that follows re‐establishment of circulation to the ischaemic rat kidney. Brain transections at bulbar and midthalamic levels did not modify the blood pressure elevation.
Several pharmacological antagonists of the sympathetic nervous system did not modify the blood pressure response. These observations are not consistent with the view that a neural element is necessary for renin release.
Constant flow perfusion of the ischaemic kidney in the intact and spinal sectioned rat was performed to evaluate haemodynamic factors involved in renin release. The pressor response was present in spinal sectioned animals under these conditions.
These results suggest that the nervous system is necessary to maintain adequate blood flow for renin ‘washout’ into the systemic circulation rather than to release renin from juxtaglomerular cells.
Oestrogen‐induced sensitization of the uterine artery of the guinea‐pig to acetylcholine
Authors: BELL C. 
Published: July 2012

Summary
It has been shown previously that a dilatation of the uterine artery of the guinea‐pig in response to acetylcholine or to stimulation of cholinergic vasodilator nerves occurs only during pregnancy. Experiments have now been performed to determine the hormonal basis of this change in responsiveness.
Chronic treatment of virgin guinea‐pigs with oestradiol, either by intramuscular injection or by subcutaneous implantation, caused the development of a responsiveness of the uterine artery to acetylcholine which was similar in degree to that occurring during pregnancy.
Simultaneous administration of progesterone did not significantly inhibit this oestrogen effect. In contrast the characteristic actions of oestrogen on uterine growth and fat catabolism were completely antagonized by progesterone.
The time course of the development of responsiveness to acetylcholine of the uterine arteries during pregnancy was parallel to the rises in oestrogen production and placental blood flow as determined by other workers. This supports the concept that cholinergic dilator nerves participate in uterine hyperaemia during pregnancy and that their functioning is regulated by the maternal blood oestrogen level.
The effects of hepatic and renal damage on paracetamol metabolism and excretion following overdosage.: A pharmacokinetic study
Authors: PRESCOTT L. F. , WRIGHT N. 
Published: July 2012

Summary
The kinetics of paracetamol metabolism and excretion were studied in 41 patients following overdosage. Acute hepatic necrosis developed in 23 patients and in 3 of these acute renal failure also occurred. Two patients died in hepatic failure.
Paracetamol metabolism was impaired in the patients with liver damage. The plasma half‐life of the unchanged drug was significantly prolonged, and the ratio of the plasma concentrations of unchanged to conjugated paracetamol was significantly higher than in the patients without liver damage.
Paracetamol and its conjugates were rapidly excreted in the urine. However, excretion was slower in patients with liver damage and a higher proportion was excreted unchanged.
The renal clearance of unchanged (but not conjugated) paracetamol was related to the urine flow rate. However, forced diuresis is of no practical value and is contraindicated on clinical grounds. There was no correlation between urine pH and clearance of unchanged or conjugated drug.
In patients with hepatic necrosis there was a marked decrease in the overall elimination rate constant which could be accounted for by decreased metabolite formation. Except in patients with acute renal failure, the urinary excretion rate constants were similar to those observed in patients without liver damage.