bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep produced by clonidine (2‐(2,6‐dichlorophenylamino)‐2‐imidazoline hydrochloride)
Authors: HOLMAN R. B. , SHILLITO ELIZABETH E. , VOGT MARTHE 
Published: July 2012

Summary
The dose of clonidine (given intravenously) required to elicit sleep in the young chick is 1/25th to 1/50th of an equiactive dose of noradrenaline. The approximate ed50 is 001 μmol/kg. Phentolamine (10–15 mg/kg, but not 5 mg/kg) antagonizes the action of both clonidine and noradrenaline.
Intensive treatment with p‐chlorophenylalanine (700 mg/kg for 3–4 days) does not prevent the hypnotic effect of clonidine in the chick, although brain 5‐HT is reduced to 15% of normal. Neither is natural sleep modified.
Sleep after clonidine is not affected by methysergide (0·1–1 μmol/kg, i.m.), but prevented by LSD (0·1–0·3 μmol/kg). The effect of LSD is interpreted as a physiological antagonism.
Clonidine (50 mg/kg) injected intravenously into adult rats causes sleep which is not abolished by phentolamine (5 mg/kg) or by p‐chlorophenylalanine in doses which interfere with natural sleep.
When, per kg body weight, the same dose of clonidine is injected into the lateral cerebral ventricle of rats, sleep ensues in more than half the animals, and persistent eating in about a third; only one of seventeen rats showed no change in behaviour. Eating and sleeping remained unaltered after p‐chlorophenylalanine. The actual dose of clonidine injected into the lateral ventricle was 0·037 μmol, amounting to about 0·15 μmol/kg or 15 times the dose required intravenously in the chick. Noradrenaline 0·15 μmol per (intraventricular) injection caused eating but no sleep, whereas higher doses produced ataxia and paresis.
The work suggests that clonidine does not elicit sleep by an action requiring the integrity of the 5‐HT‐containing neurones arising in the raphé nuclei, and that its action is not on tryptamine receptors. In the chick, sleep appears to be produced by a central sympathomimetic effect; it is possible, but not certain, that this also holds for the rat.
The intravenous hypnotic dose of clonidine for the cat is about the same as that for the rat, but injection is not accompanied by signs of peripheral sympathetic stimulation.
Comparison of the antinociceptive activities of physostigmine, oxotremorine and morphine in the mouse
Authors: PLEUVRY BARBARA J. , TOBIAS M. A. 
Published: July 2012

Summary
Morphine, oxotremorine and physostigmine showed antinociceptive activity in mice using the hot plate reaction time test.
The action of morphine, but not that of oxotremorine, was antagonized by naloxone and by nalorphine, whereas the effect of physostigmine was unaffected by naloxone and increased by nalorphine.
The antinociceptive effects of morphine and of physostigmine were increased by procedures reported to increase the ratio of 5‐hydroxytryptamine to dopamine in the brain. It was decreased by procedures reported to cause a fall in brain 5‐hydroxytryptamine or a rise in dopamine relative to 5‐hydroxytryptamine.
The antinociceptive effect of oxotremorine was potentiated by procedures reported to decrease brain noradrenaline and was unaffected by procedures altering brain 5‐hydroxytryptamine.
The results suggest differences in the mode of action of morphine and physostigmine on the one hand and of oxotremorine on the other.
Interaction in the cerebral metabolism of the biogenic amines: Effect of intravenous infusion of l‐tryptophan on the metabolism of dopamine and 5‐hydroxyindoles in brain and cerebrospinal fluid
Authors: MOIR A. T. B. 
Published: July 2012

Summary
In dogs, an intravenous injection of l‐tryptophan followed by intravenous infusion of l‐tryptophan, although unable to maintain stable concentrations of tryptophan in the plasma or cerebrospinal fluid, produced stable, raised concentrations of 5‐hydroxyindol‐3‐ylacetic acid (5‐HIAA) in the cerebrospinal fluid (c.s.f.). This indicated that it was possible to raise the concentrations of the 5‐hydroxyindoles in brain and to maintain the cerebral metabolism in a new steady state.
The regional distribution of the total molal concentration of the 5‐hydroxyindoles in brain after the administration of tryptophan was similar to the distribution found in control animals, thus suggesting the normal rate limiting step of metabolism, the activity of the enzyme tryptophan 5‐hydroxylase, was still the controlling factor.
Tryptophan administration caused a greater proportionate increase in the concentration of 5‐HIAA than in that of 5‐hydroxytryptamine (5‐HT) in all regions of brain, perhaps indicating that the ‘storage’ capacity for 5‐HT becomes filled under these conditions.
Administration of tryptophan caused a large rise in the concentration of homovanillic acid in c.s.f. demonstrating that there was an interaction between the cerebral metabolism of tryptophan and dopamine.
Interaction in the cerebral metabolism of the biogenic amines: Effect of intravenous infusion of l‐tryptophan on tryptophan and tyrosine in brain and body fluids
Authors: MOIR A. T. B. 
Published: July 2012

Summary
The distribution of the amino‐acids tryptophan and tyrosine has been determined in plasma ultrafiltrate, whole plasma, erythrocytes, cerebrospinal fluid (c.s.f.) and various regions of the brain in dogs.
The effect of tryptophan administration on the distribution of both these amino‐acids showed that the alterations produced in tryptophan concentration did not appear to change the concentrations of tyrosine from their normal pattern.
The implications of these results with regard to amino‐acid transport systems in man and dog are discussed.
Effect of p‐nitromethylamphetamine on biogenic amines and their amino‐acid precursors in rat brain
Authors: LEONARD B. E. , SHALLICE SUSAN A. 
Published: July 2012

Summary
Low doses of p‐nitromethylamphetamine caused small increases in the concentrations of brain noradrenaline and dopamine in the rat; a dose of 60 mg/kg however, caused a decrease in the concentrations of both amines. p‐Nitromethylamphetamine caused behavioural hyperexcitability only at doses which approximated to half the ld50 (68 mg/kg).
p‐Nitromethylamphetamine potentiated the action of 4,α‐dimethyl‐m‐tyramine in depleting brain noradrenaline. This suggests that it may affect brain noradrenaline concentrations by utilizing a reserpine resistant uptake mechanism.
p‐Nitromethylamphetamine decreased the concentration of brain 5‐hydroxytryptamine.
Changes in the blood and brain concentrations of tyrosine and γ‐amino‐n‐butyric acid concentration in the brain could not be correlated with the changes in brain amines. However, a rise in the concentration of brain tryptophan appeared to be correlated with the fall in brain 5‐hydroxytryptamine.
Interaction between prostaglandins and gonadotrophins in the rabbit ovary
Authors: BEDWANI J. R. , HORTON E. W. 
Published: July 2012

Summary
It has been suggested that prostaglandins function as feedback modulators of hormonal actions which are mediated by adenosine 3′,5′‐monophosphate (cyclic AMP). This hypothesis has been tested on the rabbit ovary, whose steroidogenic response to luteinizing hormone (LH) is mediated by the cyclic nucleotide.
Prostaglandin E1 (1–100 μg/ml) reduced the production of progesterone by rabbit ovaries incubated in the presence of a submaximal concentration of LH, but had no effect on the formation of this steroid when exogenous cyclic AMP was used as the stimulating agent. The prostaglandin was without effect on the formation of 20α‐hydroxypregn‐4‐en‐3‐one in the presence of either LH or cyclic AMP.
Prostaglandin E2 (1 μg/ml) was without effect on ovarian steroidogenesis in the presence of LH.
There was no evidence that exogenous prostaglandin E1 was inactivated during incubation with rabbit ovaries in the presence of LH.
Prostaglandin E‐like compounds were detected in homogenates of incubated rabbit ovaries. However, concentrations of LH sufficient to stimulate steroidogenesis did not stimulate the synthesis of these compounds by the ovary in vitro, nor their release from the ovary in vivo.
It is concluded that the prostaglandin‐like compounds detected in the ovary are unlikely to play a role in the regulation of steroidogenesis. The results of this investigation do not support the hypothesis that prostaglandins function as general modulators of hormonal actions which are mediated by cyclic AMP.
Monoamine oxidase in sympathetic nerves: a transmitter specific enzyme type
Authors: GORIDIS C. , NEFF N. H. 
Published: July 2012

Summary
When rat brain or superior cervical ganglion monoamine oxidase was incubated with increasing concentrations of clorgyline, using tyramine as substrate, the inhibition of the enzyme could be represented by a pair of sigmoidal curves joined by a horizontal region where inhibition was constant. Tyramine appeared to be metabolized by two enzymes, one of which was highly sensitive to clorgyline, designated A, whereas the other enzyme, designated B, was less sensitive to clorgyline.
The ratio of A/B activity for brain was 6/4 while in the ganglion it was 9/1.
When the experiments were repeated using noradrenaline as the substrate, the inhibition of the enzyme followed a simple sigmoidal curve where deamination was inhibited by low concentrations of clorgyline as observed with enzyme A.
We conclude that tyramine is deaminated by both A and B enzymes whereas noradrenaline is deaminated only by enzyme A, the enzyme which is most active in the ganglion. Our observations are consistent with the hypothesis that a specific intraneuronal monoamine oxidase plays an important role in the catabolism of noradrenaline in sympathetic nerves.
Preparation and assay of urogastrone, an inhibitor of gastric acid secretion
Authors: LAWRENCE A. J. , SCHILD H. O. , SMITH G. M. 
Published: July 2012

Summary
Urogastrone, an acid gastric secretion inhibitor extracted from human urine, was assayed in the anaesthetized rat by circulating through its stomach a succinic‐propionic buffer and recording electrometrically the secretion of acid in response to carbachol, and inhibition of carbachol secretion by urogastrone.
Quantitative assay procedures are described requiring the administration of only one or two doses of urogastrone to each rat.
An extraction procedure for urogastrone is described based on the use of zeocarb, a cationic polystyrene resin.
The most purified samples contained 40–80 times the amount/milligram which was just detectable by the assay method.
β‐Adrenoceptor antagonist activity of 3‐methoxyisoprenaline
Authors: BASSETT J. R. 
Published: July 2012

Summary
The β‐adrenoceptor antagonist activity of 3‐methoxyisoprenaline, the O‐methylated metabolite of isoprenaline, was studied on isolated driven atrial strip and tracheal chain preparations of the guinea‐pig and on the hind limb blood flow of the dog.
On both the atrial strip and tracheal chain preparations the blockade of responses to isoprenaline fulfilled the criteria for simple competitive inhibition.
3‐Methoxyisoprenaline decreased the vasodilator response to isoprenaline in the dog hind limb, but did not affect the response to noradrenaline.
3‐Methoxyisoprenaline had about 1/3,700 of the potency of propranolol as a β‐adrenoceptor antagonist on the tracheal chain preparation, 1/1,000 on the atrial strip preparation and less than 1/400 on the hind limb blood flow.
The antagonist activity of 3‐methoxyisoprenaline showed a slight specificity for cardiac β‐adrenoceptors, being 4.3 times more active on guinea‐pig atria than on trachea.
Although 3‐methoxyisoprenaline antagonized the actions of isoprenaline in the three preparations, its activity was extremely weak. It is unlikely that the formation of 3‐methoxyisoprenaline from isoprenaline, administered therapeutically, could lead to β‐adrenoceptor blockade.
Cardiovascular effects of toxins isolated from the cnidarian Chironex fleckeri Southcott
Authors: FREEMAN SHIRLEY E. , TURNER R. J. 
Published: July 2012

Summary
Two unstable high molecular weight toxins have been isolated from tentacles of Chironex fleckeri by exclusion chromatography. Both are cardiotoxic; the lower molecular weight fraction is also a potent haemolysin.
Both toxins reduce the rate, amplitude of contraction and coronary flow in the isolated, perfused guinea‐pig heart. Relative to the mouse lethal dose the haemolytic fraction is less potent in this preparation than the purely cardiotoxic fraction.
Both toxins cause a rise in arterial pressure in anaesthetized rats and rabbits by a direct action on the vascular musculature. This is followed by hypotension, bradycardia and cardiac irregularity. An increase in respiratory rate is followed by apnoea of variable duration, which is associated with a rise in arterial pressure. Animals frequently show arterial pressure oscillations with periods of apnoea interspersed with hyperpnoea.
The carotid occlusion reflex is depressed during hypotensive periods after both toxins, although (–)‐noradrenaline can still elicit a marked pressor response. Bilateral cervical vagotomy has but little effect on the response to either toxin. save to prevent hyperpnoea, but radical denervation of sinoaortic afferents reduces the arterial pressure fall after the initial hypertensive response, suggesting that this fall is due to a combination of baroreceptor stimulation and a fall in cardiac output. Blood pressure oscillations are still seen, possibly due to central stimulation by hypercapnia.
Interference with the efferent arm of the vasomotor reflex arc with hexamethonium, bretylium or phenoxybenzamine either abolishes or markedly reduces the blood pressure oscillations without affecting the initial hypertensive response.
The cardiovascular effects of the two toxins are thought to be due to direct vasoconstriction, cardiotoxicity, baroreceptor stimulation and possibly depression of the vasomotor centre. The resultant disordering of the feed‐back system regulating vasomotor tone leads to the characteristic arterial pressure oscillations.
The inhibition by dexamethasone and disodium cromoglycate of anaphylactic bronchoconstriction in the rat
Authors: CHURCH M. K. , COLLIER H. O. J. , JAMES G. W. L. 
Published: July 2012

Summary
. A method for the measurement of anaphylactic bronchoconstriction in the rat is described.
. Dexamethasone inhibited this response in a dose‐related manner.
. Disodium cromoglycate antagonized the response. A bell‐shaped dose‐response curve was obtained with peak activity at 1 mg/kg i.v.
. Meclofenamate was not active when given alone or in combination with dexamethasone.
. Methysergide significantly inhibited the response. Mepyramine, atropine, propranolol and adrenalectomy did not significantly modify the response.
. The relationships of anaphylactic bronchoconstriction in the rat to anaphylactic bronchoconstriction in the guinea‐pig and to human asthma are discussed.
The rat isolated colon as a specific assay organ for angiotensin
Authors: GAGNON D. J. , SIROIS P. 
Published: July 2012

Summary
. The antagonism of the contractile effects of prostaglandins F2α and E2 by polyphloretin phosphate (PPP) was studied on the rat isolated colon.
. PPP (20 μg/ml) was found to reduce the myotropic action of angiotensin I (10 ng/ml) and II (0·3 ng/ml) whereas larger doses of both agents were not influenced.
. It is concluded that when a mixture of antagonists is used, including PPP, the rat isolated colon can be used to assay angiotensin with accuracy and specificity. The addition of 8‐L‐ala‐ATII affords a further test of specificity.
Release of monoamines from the striatum and hypothalamus: Effect of γ‐hydroxybutyrate
Authors: BUSTOS G. , ROTH R. H. 
Published: July 2012

Summary
. A simple in vitro system was developed to study the effect of γ‐hydroxybutyrate on nerve cell depolarization‐induced release of labelled dopamine, noradrenaline and 5‐hydroxytryptamine from brain slices.
. The release of 3H‐dopamine formed in rat striatal slices incubated with 3H‐tyrosine was followed either by transferring the slices through successive media or by using a superfusion system. A one to three minute exposure to K+ (53 mm) caused up to a thirty fold increase in the release of newly synthesized 3H‐dopamine. This K+‐induced release was antagonized when γ‐hydroxybutyrate (1 × 10−3m) was present in the medium.
. Potassium (53 mm) increased (eighteen to thirty fold) the release of 3H‐dopamine from striatal slices initially loaded by preincubation with 3H‐dopamine. However, the K+‐induced release of this pool of dopamine was not antagonized by γ‐hydroxybutyrate.
. Potassium (53 mm) also increased the release from striatal slices of 3H‐5‐hydroxytryptamine newly synthesized from 3H‐tryptophan. This K+‐induced release of 5‐hydroxytryptamine was also not inhibited by γ‐hydroxybutyrate.
. The release of newly synthesized 3H‐noradrenaline from hypothalamic slices was also increased by K+. This K+‐induced release, however, unlike that of 5‐hydroxytryptamine, was antagonized when γ‐hydroxybutyrate was present in the superfusion medium.
. Removal of Ca++ had no effect on K+‐induced release of 3H‐dopamine when followed by transferring the slices through successive media. This K+‐induced release was abolished, however, when Mg++ (12 mm) was present in the medium.
. The removal of Ca++ from the superfusion medium abolished almost completely the K+‐induced release from striatal slices of either newly synthesized 3H‐dopamine or preloaded 3H‐dopamine. This is presumably due to a more effective washout of tissue Ca++ by the superfusion technique.
. The ability of γ‐hydroxybutyrate to antagonize the K+‐induced release of monoamines from brain slices does not appear to be unique to the release of newly synthesized dopamine from the striatum.
Monoamine mediation of the morphine‐induced activation of mice
Authors: CARROLL BERNARD J. , SHARP PETER T. 
Published: July 2012

Summary
. The dose‐response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established.
. The activation response can be modified by drugs which affect either catecholamines or indoleamines.
. The monoamine precursors l‐DOPA and 5‐hydroxytryptophan potentiate the response.
. The monoamine synthesis inhibitors α‐methyl‐p‐tyrosine and p‐chlorophenylalanine reduce the response.
. Inhibition of monoamine oxidase activity by pargyline caused a great increase in the response. The simultaneous administration of reserpine resulted in a further potentiation.
. Reserpine blocked the response whenever it was given alone, either before, with or after the injection of morphine.
. Blockade of α‐adrenoceptors with phentolamine or phenoxybenzamine reduced the response.
. Blockade of tryptaminergic receptors with methysergide or cinanserin also antagonized the response.
. The major tranquillizers haloperidol and chlorpromazine reduced the response. Haloperidol was especially effective in this regard.
. The tricyclic antidepressant drug imipramine potentiated the response.
. The morphine antagonist nalorphine completely prevented the response.
. The anticholinergic agent atropine and the antihistaminic drug mepyramine did not affect the response.
. We conclude that dopamine, noradrenaline and 5‐hydroxytryptamine are all involved in the normal activation response of grouped mice to morphine, with dopaminergic mechanisms being of primary importance.
Antagonism of noradrenaline and histamine by desipramine in the isolated artery of the rabbit ear
Authors: McCULLOCH M. W. , STORY D. F. 
Published: July 2012

Summary
. The effects of desipramine (DMI) were examined on the vasoconstrictor responses of the isolated perfused artery of the rabbit ear to noradrenaline (NA) and to histamine. Innervated and sympathetically denervated arteries were used.
. In innervated arteries, DMI in concentrations of 1 × 10−8 to 1 × 10−7m enhanced the responses to NA; higher concentrations reduced the responses. In sympathetically denervated arteries, DMI caused only reduction of the responses to NA.
. Responses to histamine were reduced by DMI in both innervated and denervated arteries. DMI was considerably more potent as an antagonist of histamine than of noradrenaline.
. The reduction by DMI of the responses to NA and histamine in both innervated and denervated arteries was associated with a parallel shift to the right of the concentration‐response curves of the agonist and a depression of the maximal response. These effects of DMI were reversible.
. Analysis of the data by the method of Arunlakshana & Schild (1959) showed the following: the antagonism of the action of NA by DMI on denervated arteries fulfilled the requirements for competitive antagonism; antagonism of the action of NA on innervated arteries was not competitive; antagonism of the actions of histamine on innervated and denervated arteries was not competitive.
. It is suggested that DMI antagonizes the action of NA and histamine on the perfused artery of the rabbit ear in two ways: (i) reversible specific antagonism which is competitive for NA and not competitive for histamine; (ii) reversible non‐specific antagonism which is non‐competitive for both agonists.
Activation of arginine and tyrosine esterase in serum from patients with hereditary angio‐oedema
Authors: EISEN V. , LOVEDAY C. 
Published: July 2012

Summary
. The role of clotting factor XII in the activation of the complement subunit C1s to C1 esterase was examined.
. In sera from patients with hereditary angio‐oedema who lack the α2‐glycoglobulin C1 inhibitor, silicates and other potent activators of clotting factor XII induced far less C1 esterase activity than did the weaker factor XII activators, carrageenin and cellulose sulphate. In contrast, the intensity of the induced plasma kallikrein activity corresponded more closely to the clot‐promoting effect of the factor XII activators.
. Spontaneous generation of C1 esterase activity was only slightly delayed in hereditary angio‐oedema sera previously depleted of factor XII. In normal sera, C1 esterase did not develop spontaneously and could not be induced.
. Experiments with inhibitors suggested that the spontaneous activation of Cls may consist of two phases: factor XII and other plasma proteases first activate small amounts of C1s; the resulting C1 esterase then activates the bulk of C1s. The observed spontaneous activation suggests that when fully activated, the C1s present in 1 ml of human serum will hydrolyse 1–2 μmol of ATEe/minute.
Time‐dose relationships for locomotor activity effects of morphine after acute or repeated treatment
Authors: BABBINI M. , DAVIS W. M. 
Published: July 2012

Summary
. Effects of morphine sulphate (1·25, 2·5, 5, 10, 20 and 40 mg/kg i.p.) on locomotor activity of male rats were observed for 8 h after single doses in non‐tolerant rats. The lower three doses had only an excitatory effect, whereas the higher three doses caused initial depression followed by a delayed excitatory effect.
. The same doses of morphine were administered daily for 30 days. No tolerance developed within this time to the excitatory effect. The locomotor excitatory effect of the higher three doses of morphine became progressively more pronounced over treatment periods of 30 days (and 48 days for 20 mg/kg), while the latency to peak activity decreased.
. An explanation of these results is suggested on the basis of two different central drug‐receptor interactions affecting motility.
The effects of isoprenaline and noradrenaline on pentagastrin‐stimulated gastric acid secretion and mucosal blood flow in the dog
Authors: CURWAIN B. P. , HOLTON PAMELA 
Published: July 2012

Summary
. Isoprenaline (0·02 to 2·0 μg kg−1 min−1) inhibited gastric secretion in response to pentagastrin in both conscious and anaesthetized dogs and in response to feeding in conscious dogs.
. The inhibition was unaffected during cardiac β‐adrenoceptor blockade by propranolol.
. The inhibition was not due to decreased mucosal blood flow.
. This effect of isoprenaline is different from its effect on histamine‐induced gastric secretion.
. Noradrenaline (0·05–2·0 μg kg−1 min−1) also decreased gastric secretion but it was less effective than isoprenaline.
. The mechanism of action of noradrenaline is probably a decrease in mucosal blood flow.