bluuebunny/crossref_metadata_2025 huggingface dataset:
Decarboxylases of histidine and ornithine in chick embryo
Authors: DZODZŒ YAO C. G. , ROSENGREN ELSA
Published: July 2012

The activities of histidine and ornithine decarboxylases as well as the histamine content of the developing chick embryo were studied.

Histidine decarboxylase (l‐histidine carboxy‐lyase; E.C. 4.1.1.22) activity was fairly low with a tendency to increase at later stages of development. This enzyme was preferentially present in the supernatant fraction of the tissue homogenate. α‐Methyl‐histidine, but not α‐methyl‐DOPA, inhibited its activity.

The histamine content per gramme of embryo was low with a tendency to increase with the age of the embryo.

Ornithine decarboxylase (l‐ornithine carboxy‐lyase; E.C. 4.1.1.17) activity was high at the beginning of the stages of development investigated, but later there was a steep fall in activity. A noticeable feature was that while the activity in the residual fraction of the homogenate remained almost constant during development, the activity in the supernatant fraction was high in the early stages, then fell rapidly to nearly zero at later stages.
Cardiorespiratory effects of intravenous isoprenaline and salbutamol in dogs
Authors: LOH L. , SEED R. F. , SYKES M. K.
Published: July 2012

The cardiorespiratory effects of intravenous infusions of isoprenaline and salbutamol (1 and 5 μg/min) have been compared in twelve dogs.

Both drugs produced a rise in pulse rate, a fall in systemic arterial pressure and a rise in pulmonary arterial pressure. Salbutamol produced a greater increase in cardiac output than isoprenaline.

Both drugs produced an increase in venous admixture, but a significant fall in arterial oxygen tension occurred only with isoprenaline at the higher dose.
Central autonomic effects of prostaglandin F2α on the cardiovascular system of the dog
Authors: LAVERY HELEN A. , LOWE R. D. , SCROOP G. C.
Published: July 2012

Prostaglandin F2α infused into the vertebral artery of the anaesthetized greyhound in doses which had no effect when given intravenously ((8–64 ng/kg)/min) caused an increase in blood pressure and heart rate.

This response was not significantly altered by β‐adrenoceptor blockade with propranolol (10 mg i.v.) or by cervical cord section at C4–6.

The tachycardia was abolished and the pressor response greatly reduced by vagotomy or atropine (250 μg/kg i.v.).

The pressor response which remained after vagotomy was abolished by subsequent sympathetic blockade with bethanidine (2–3 mg/kg i.v.) or bretylium (10 mg/kg i.v.).

In contrast to the effects of propranolol or cervical cord section bethanidine (4–5 mg/kg i.v.) or bretylium (10 mg/kg i.v.) significantly reduced blood pressure and heart rate responses to intravertebral prostaglandin F2α. This result suggests that bethanidine and bretylium have some central actions.

It is concluded that the cardiovascular effects of intravertebral infusions of prostaglandin F2α are mediated by the autonomic nervous system and that the preferential pathway is withdrawal of vagal tone to the heart.
Quantitative analysis on isolated organs of the autonomic blocking properties of indoramin hydrochloride (Wy 21901)
Authors: ALPS B. J. , HILL MADELINE , JOHNSON E. S. , WILSON A. B.
Published: July 2012

Indoramin is a competitive α‐adrenoceptor blocking agent on the guinea‐pig isolated vas deferens and aortic strip; the pA2 value on the aorta is 7·4.

Indoramin is devoid of β‐adrenoceptor blocking activity on the guinea‐pig isolated trachea (10–4m) and the Langendorff preparation of the rabbit heart (10−6m). It also has no adrenergic neurone blocking action on the Finkleman preparation of the rabbit small intestine (10−5m).

On the Langendorff preparation of the rabbit isolated heart, indoramin (above 10−6m) has cardio‐inhibitory properties similar to those of propranolol.

On the guinea‐pig isolated ileum (10−5m) and trachea (10−6m), indoramin is devoid of anticholinergic activity, but has a potent antihistamine action which satisfies the criteria for competitive antagonism; the pA2 value for this antagonism on the ileum is 8·2.

Indoramin antagonizes 5‐hydroxytryptamine on the rat isolated fundus and ileum; the pA2 value for the antagonism on the ileum is 60.
Effect of β‐adrenoceptor blocking agents on poststimulatory atrial flutter in the dog, with observations on the participation of adrenergic mechanisms in this experimental arrhythmia
Authors: MADAN B. R. , SONI R. K.
Published: July 2012

Four β‐adrenoceptor antagonists,viz.(±) propranolol (0·5 mg/kg), (—) alprenolol (0·25 mg/kg), practolol (5 mg/kg) and USVC 6524 (20 μg/kg), were tested for their effects on atrial flutter produced by electrical stimulation of the right atrium around the crushed inter‐venae‐caval bridge in anaesthetized dogs.

All the drugs reduced atrial and ventricular rates; this was followed by the abrupt termination of flutter and restoration to normal sinus rhythm.

Since all the drugs (including practolol, which is devoid of local anaesthetic activity) were given in doses just sufficient to block β‐adrenoceptors, it indicated that β‐adrenoceptor blockade was responsible for their antiarrhythmic property in this test procedure.

Further evidences in support of participation of the sympathetic nervous system in poststimulatory flutter were: (i) flutter could not be produced in nine out of ten dogs whose catecholamine stores were depleted by pretreatment with reserpine; (ii) infusion of adrenaline in these animals resulted in the production of flutter; (iii) duration of flutter after termination of exposure to adrenaline was a few minutes, which is similar to the brief time previously reported to be taken for the disappearance of catecholamines from the hearts of reserpinized animals.

The clinical significance of the above findings is discussed.
Some pharmacological properties of piperazine
Authors: MASON P. A. , STURMAN GILLIAN
Published: July 2012

The action of piperazine on mammalian smooth, cardiac and skeletal muscles has been studied.

Piperazine increased tone and produced a dose dependent contraction of isolated smooth muscle, which was antagonized by atropine.

With cardiac muscle, piperazine depressed both the rate and force of contraction and was antagonized by atropine. At higher concentrations, a non‐specific depression of cardiac muscle was found. The intravenous injection of piperazine produced a transient decrease in both heart rate and blood pressure and this was followed by an increase.

In about half of the mammalian skeletal muscle preparations, piperazine potentiated the twitch of the muscle evoked by electrical stimulation.

On the frog neuromuscular preparation, piperazine produced potentiation of the twitch but this was followed first by blockade of the effects, of nerve stimulation and then by depression of the effects of direct muscle stimulation.
Developmental characteristics of brain catecholamines and tyrosine hydroxylase in the rat: effects of 6‐hydroxydopamine
Authors: BREESE G. R. , TRAYLOR T. D.
Published: July 2012

Brain noradrenaline, dopamine and tyrosine hydroxylase were found in rat brain a few days before birth and increased progressively until reaching adult values. The most rapid period of growth for these substances seemed to occur between 7 and 18 days.

The intracisternal administration of 6‐hydroxydopamine to rats 7 days of age reduced concentrations of noradrenaline, dopamine, and tyrosine hydroxylase by 72 hours.

The concentrations of noradrenaline, dopamine or tyrosine hydroxylase in rats that received 6‐hydroxydopamine at 7 or 14 days of age remained markedly reduced when determined at adulthood, indicating that fibres did not continue to develop after the administration of this compound. The rats treated at 7 days also showed diminished concentrations of noradrenaline in heart.

Rats injected with 6‐hydroxydopamine at 7 days had reduced body weight as well as a reduction of some organ weights. This growth deficit was not observed in animals that received this drug at 14 days of age.

The administration of ovine growth hormone to rats that received 6‐hydroxydopamine at 7 days did not reverse the growth deficiency in these animals.
Long‐lasting peripheral and central effects of 6‐hydroxydopamine in rats
Authors: CLARK D. W. J. , LAVERTY R. , PHELAN E. L.
Published: July 2012

In newborn rats treated with 6‐hydroxydopamine hydrobromide (6‐OHDA) (50–150 mg/kg on 5–7 days) a widespread and long‐lasting dose related sympathectomy was demonstrated.

When rats given 6‐hydroxydopamine (100 mg/kg, seven treatments) in the neonatal period were killed at 10 weeks the concentration of noradrenaline (NA) in the heart, mesentery and vas deferens was significantly reduced. There was no alteration in the catecholamine content of the adrenal glands.

The amplitude of the responses of perfused mesenteric arteries from 6‐hydroxydopamine treated rats to intra‐arterial noradrenaline was not increased, compared with controls, but the duration of responses was increased.

6‐Hydroxydopamine given to newborn rats caused a long‐lasting depletion of noradrenaline in three of the five regions of the central nervous system (cortex, cerebellum and spinal cord) studied. The concentration of noradrenaline in the pons‐medulla was increased, but in the thalamic region was unchanged. The treated rats showed significantly lower exploratory activity.

Treatment of newborn rats with 6‐hydroxydopamine thus has striking and long‐lasting effects on peripheral and central adrenergic systems.
Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism
Authors: PATON W. D. M. , PERTWEE R. G.
Published: July 2012

Cannabis extract prolonged sleeping time in mice in a thermally neutral environment (30–32° C) in which hypothermia does not occur. The prolongation was dose related, just detectable at 50 mg/kg, and 4‐fold at 500 mg/kg.

Under these conditions, ether sleeping time was not prolonged.

Cannabis extract inhibited the aerobic metabolism of phenazone by a microsome‐rich 9,000 g supernatant of mouse liver homogenate capable of nicotinamide adenine dinucleotide phosphate (NADPH) generation.

Δ1‐Tetrahydrocannabinol (Δ1‐THC) prolonged pentobarbitone sleep and inhibited phenazone metabolism, but its action was limited, and could not account for the effect of the extract. The carotenes and water‐soluble fractions of the extract were inactive on pentobarbitone sleep.

Cannabidiol was strongly active by both tests; in vivo 39·8 μm/kg (12·5 mg/kg) prolonged sleep by 190%, and in vitro 12·7 μm inhibited phenazone metabolism 20%. These actions were dose related, and could account for the effect of the extract.

The prolongation of pentobarbitone sleep by cannabis extract in a dose of 200 mg/kg, intraperitoneally, was maximal when given 30 min before the pentobarbitone, still present at 3 h, but undetectable at 24 hours. No phase of enhanced metabolism at 24 or 48 h after single cannabis injection was detected.

It is concluded that cannabis extract inhibits microsomal activity of mouse liver, chiefly by virtue of its cannabidiol content. It is probable that cannabis consumption by man could lead to altered disposal of many other drugs, used in medicine or otherwise.
Effects of muscarine given into the brain of fowls
Authors: MARLEY E. , SELLER T. J.
Published: July 2012

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

. 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

. 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

(—)‐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

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

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

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

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

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

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

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

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

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

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

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

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.
The use of the hamster stomach in vitro as an assay preparation for prostaglandins
Authors: UBATUBA F. B.
Published: July 2012

Hamster stomach strips in vitro are useful test preparations for the assay of prostaglandins E and F in the nanogram concentration range. Three‐minute cycles can be used for long periods without spontaneous contractions or significant base‐line instability.

The mean percentage error and the precision index of six 4‐point assays of prostaglandin E2 were 7·8 and 0·057, respectively.

The relative sensitivity to different prostaglandins was E2/E1∼1, E2/F1α∼65 and E2/A1∼400.

These preparations were relatively insensitive to 5‐hydroxytryptamine (prostaglandin E2/5‐HT∼20,000) and histamine (prostaglandin E2/histamine∼200).

These results suggest that the hamster stomach preparation can be used to differentiate between 5‐hydroxytryptamine and prostaglandins.
THE EFFECT OF INDOMETHACIN ON THE CARDIOVASCULAR AND METABOLIC RESPONSES TO E. coli ENDOTOXIN IN THE CAT
Authors: PARRATT J.R. , STURGESS R.M.
Published: July 2012

The response of pentobarbitone‐anaesthetized cats to the intravenous administration of E. coli endotoxin (2 mg/kg) consisted of acute pulmonary vasoconstriction (3–5 min after the injection) and a secondary shock phase characterized by delayed systemic hypotension, decreased central venous pressure and cardiac output, and metabolic acidosis with arterial lactate levels three to four times normal. Only one of 25 animals survived 6 hours.

Indomethacin (10 mg/kg), administered intravenously 30 min before the endotoxin, reduced both systemic arterial pressure and myocardial blood flow. It abolished the pulmonary vasoconstriction induced by endotoxin.

Indomethacin modified some of the characteristic features of the delayed, endotoxin shock phase. Systemic hypotension was not observed and the blood pressure in the indomethacin‐treated cats 1, 2 and 4 h after endotoxin was 30 mmHg higher than in those cats administered endotoxin alone. The decrease in arterial pH was also significantly delayed. Six out of 15 animals survived 6 hours.

It is suggested that indomethacin may abolish the initial pulmonary hypertension and oedema by antagonizing the release, or vasoconstrictor effect, of histamine and that part of its action during the shock phase is due to inhibition of prostaglandin release.
PROSTAGLANDINS, KININ AND INFLAMMATION IN THE RAT
Authors: THOMAS G. , WEST G.B.
Published: July 2012

Prostaglandin E1 and bradykinin exert synergistic effects on vascular permeability in rat skin and in rat paws. Prostaglandin E2 is inactive in this respect.

Prostaglandin F2α reduces the bradykinin response in rat skin but not in rat paws. It also markedly reduces the response of the skin to dextran, 5‐hydroxytryptamine and histamine.

Prostaglandin E1 and dextran exert synergistic effects in rat skin when threshold doses of each agent are used.

Rats genetically resistant to dextran fail to respond to intradermal dextran in the presence of prostaglandin E1.
MECHANISM OF THE PRO‐INFLAMMATORY ACTIVITY OF SYMPATHOMIMETIC AMINES IN THERMIC OEDEMA OF THE RAT PAW
Authors: GREEN K.L.
Published: July 2012

Thermic oedema induced by heating rat paws at 46.5°C was potentiated by local injection of adrenaline, noradrenaline or high doses of isoprenaline. The pro‐inflammatory effect of sympathomimetic amines was antagonized by phenoxybenzamine or phentolamine but not by propranolol.

The subcutaneous space of heated rat paws was perfused with Tyrode solution and the perfusate collected and assayed for bradykinin, bradykininogen, kinin‐forming activity and kininase activity. When adrenaline (0.5 μg/ml) was included in the perfusion fluid, kininase activity of the perfusate was increased by 76% and free bradykinin reduced by 46%.

Increased vascular permeability induced by injection of bradykinin or kallikrein was reduced by adrenaline or noradrenaline, but isoprenaline had no significant effect.

Pretreatment with soya bean trypsin inhibitor (SBTI) or heparin did not antagonize the pro‐inflammatory effect of adrenaline or thermic oedema per se.

Potentiation of thermic oedema similar to that induced by sympathomimetic amines was obtained by injecting paws with vasopressin prior to heating, or by applying a ligature to stop blood flow to the paw for the first 15 min of heating.

Thermistor probes inserted beneath the paw skin showed that sympathomimetic amines increased the internal temperature of heated paws. This was significant, as small changes in temperature had a marked effect on the development of thermic oedema.

It is suggested that sympathomimetic amines potentiate thermic oedema of rat paws heated at 46.5°C by reducing blood flow to the paw, thereby causing a greater rise in paw temperature and consequently greater injury.
THE EFFECT OF LITHIUM AND RELATED METAL IONS ON THE URINARY EXCRETION OF 2‐OXOGLUTARATE AND CITRATE IN THE RAT
Authors: BOND P.A. , JENNER F.A.
Published: July 2012

Administration of lithium ions to rats, either acutely by intraperitoneal injection or chronically in food, causes increased excretion of 2‐oxoglutarate and citrate.

Chronic administration in food of rubidium and caesium causes decreased excretion of 2‐oxoglutarate and citrate.

The effects described are not due to changes in urine volume, nor pH, nor are they simply related to the excretion of the injected ion.

Acute administration of lithium caused an increased level of 2‐oxoglutarate in kidney and reduced the ratio of glutamate to 2‐oxoglutarate.

Renal gluconeogenesis in slices was only slightly affected by either acute administration of lithium to the animals or by its presence in the incubation medium of renal slices.
STUDIES ON THE CORONARY DILATOR ACTIONS OF SOME ADENOSINE ANALOGUES
Authors: COBBIN L.B. , EINSTEIN ROSEMARIE , MAGUIRE M. HELEN
Published: July 2012

The cardiovascular actions of 23 adenosine analogues have been examined in anaesthetized open thorax dogs; the analogues were substituted in the 2‐position of the purine ring, or in the exocyclic amino group, or were modified in the imidazole or sugar rings.

The effects of these compounds on coronary blood flow, peripheral blood pressure, and heart rate were compared with those of adenosine.

9‐β‐d‐Arabinofuranosyladenine had no cardiovascular action; the other analogues on intra‐atrial administration caused an immediate increase in coronary blood flow, the magnitude and duration of which varied with the structures of the analogues.

2‐Fluoro‐, 2‐bromo‐, 2‐isobutylthio‐, 2‐ethylamino‐, and 5′‐deoxy‐5′‐chloro‐ adenosines had coronary dilator potencies equal to or greater than that of adenosine. No relationship was found between the dilator potency of the adenosine analogues and their duration of coronary dilator action.

The coronary dilator action of adenosine was potentiated by inosine, 9‐β‐d‐arabinofuranosyladenine, tubercidin, N6‐methyladenosine and 2‐trifluoromethyl‐N6‐methyladenosine.

There was no correlation between the substrate specificities of the shorter‐acting analogues for adenosine deaminase or adenosine kinase and their duration of coronary dilator action.

It is proposed that in the anaesthetized dog, uptake into tissues is a more important mode of removal of adenosine and adenosine analogues from the vascular system than in activation by adenosine deaminase, that the duration of coronary dilator action of the analogues is related primarily to their specificity for the carrier which mediates adenosine uptake, and that the adenosine carrier is not associated with kinase action.
THE RESPONSE OF THE CAT ANOCOCCYGEUS MUSCLE TO NERVE OR DRUG STIMULATION AND A COMPARISON WITH THE RAT ANOCOCCYGEUS
Authors: GILLESPIE J.S. , McGRATH J.C.
Published: July 2012

The cat anococcygeus muscle is shown to possess a dual innervation similar to the rat anococcygeus, with a motor adrenergic innervation and an inhibitory innervation whose transmitter is unknown. The pharmacological properties of the cat muscle were investigated and compared with those of the rat muscle.

The cat muscle contracts to noradrenaline, 5‐hydroxytryptamine, tyramine, amphetamine, guanethidine, cocaine and lysergic acid diethylamide (LSD). The effects of noradrenaline and 5‐hydroxytryptamine are blocked by phentolamine and methysergide respectively.

The cat anococcygeus is relaxed by acetylcholine, carbachol, isoprenaline, ATP, prostaglandins E1, E2 and F2α and vasopressin, all of which contract the rat muscle. The effects of acetylcholine and carbachol are blocked by atropine and those of isoprenaline by propranolol.

Field stimulation produces contraction of the cat anococcygeus, which is blocked by phentolamine and guanethidine but unaffected by hexamethonium, atropine or neostigmine.

In the presence of guanethidine (10−5m), the tone of the muscle is raised and field stimulation produces relaxation of the muscle. These inhibitory responses are unaffected by phentolamine, hexamethonium, atropine or neostigmine.

Neostigmine potentiates the effects of acetylcholine, but not of carbachol in relaxing the cat anococcygeus and in contracting the rat anococcygeus, but has no effect on either motor or inhibitory responses to field stimulation.

Cold storage for up to eight days had little effect on either the motor response to noradrenaline or the motor or inhibitory response to field stimulation of the cat anococcygeus. Beyond eight days, the response to field stimulation diminishes more rapidly than the response to noradrenaline.
INTERACTION BETWEEN PIPERAZINE AND CHLORPROMAZINE
Authors: STURMAN GILLIAN
Published: July 2012

The interaction between piperazine and chlorpromazine has been studied in rats and mice. Piperazine administered a few hours previously potentiated the action of chlorpromazine on the central nervous system. No such interaction was found between piperazine and prochlorperazine.
THE ACTIONS OF PROSTAGLANDINS E2 AND F2α ON HUMAN FOETAL INTESTINE
Authors: HART S.L.
Published: July 2012

Human foetal small and large intestine responded to prostaglandins E2 and F2α, the gestational age of the tissue being between 14 and 26 weeks. The predominant response to both prostaglandins was a contraction of each region of the intestine studied. The response to both prostaglandins was antagonized selectively by polyphloretin phosphate.
THE EFFECT OF Δ1‐TETRAHYDROCANNABINOL ON THE RELEASE OF [3H]‐(‐)‐NORADRENALINE FROM THE ISOLATED VAS DEFERENS OF THE RAT
Authors: GRAHAM J.D.P. , LEWIS M.J. , LI D.M.F.
Published: July 2012

The amount of tritium released upon transmural stimulation of the isolated vas of the rat incubated with [3H]‐Δ1‐tetrahydrocannabinol (THC) (2.8 μM) was significantly greater than the non‐stimulated overflow.

There was no difference between non‐stimulated overflow and the effect of transmural stimulation of vasa equilibrated with [14C]‐sorbitol (6.5 mg/ml).

The difference between non‐stimulated and stimulated efflux from vasa equilibrated with [3H]‐Δ1‐THC was abolished in rats pretreated for 24 h with 6‐hydroxydopamine (250 mg/kg).

The amount of tritium released upon transmural stimulation of the vas incubated with [3H]‐noradrenaline (6 μm) was significantly greater than the non‐stimulated overflow.

Δ1‐THC (560 Nm and 14 μm) caused a significant dose‐dependent reduction of both non‐stimulated and stimulated tritium efflux, especially the latter.
COMPARISON OF THE EFFECTS OF PROPRANOLOL AND ICI 66082 IN BLOCKING THE RENIN RELEASING EFFECT OF RENAL NERVE STIMULATION IN THE CAT
Authors: JOHNS E.J. , SINGER BERTHA
Published: July 2012

The comparative effectiveness of propranolol and ICI 66082, in inhibiting the release of renin from the kidney resulting from renal nerve stimulation, has been studied in the cat. Over the dose range 0.17–0.68 × 10−5 mol/kg propranolol there was a dose‐response relationship with the increase of plasma renin activity (PRA) achieved after 10 min stimulation. Over the dose range 0.75–1.69 × 10−5 mol/kg ICI 66082 also inhibited the release of renin caused by nerve stimulation, but was about five times less effective than propranolol. It would appear from these data that the β‐adrenoceptors within the kidney mediating renin release are distinctly different from those of the heart.