bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of metals on the S‐S polypeptide receptor in depolarized rat uterus
Authors: SCHILD H. O. 
Published: July 2012

. Metals potentiate the contractile effects of S‐S polypeptides in depolarized rat uterus. Their order of potency is Co++ ≥ Co+++ ≥ Mn++ ≥ Ni++ ≥ Mn+++ > Zn++ ≥ Mg++ > Fe++ > Fe+++ ≥ Ca++ > Be++ = Sr++ = Ba++ = Cu++ = O.
. S‐S polypeptides with relatively weak oxytocic activity such as lys‐vasopressin, arg‐vasopressin and orn‐vasopressin are strongly potentiated by metals while highly active polypeptides such as oxytocin are weakly potentiated.
. Potentiation by metals was specific for S‐S polypeptides; other polypeptides (bradykinin, hypertensin) as well as acetylcholine and isoprenaline were unaffected.
. Potentiation by metals occurs rapidly and is fully reversible. In all cases some activity was retained by S‐S polypeptides even in the complete absence of metals.
. A scheme which could account for the observed effects has been formulated. This assumes the formation of a ternary complex between receptor, metal and polypeptide leading to improved alignment between polypeptide and receptor.
. Analogies are discussed between metal enzymes and the S‐S polypeptide receptor for which the term metal receptor is proposed.
Relationship between acetylcholine synthesis and its concentration in rat cerebral cortex
Authors: SHARKAWI MAHMOUD , SCHULMAN M. P. 
Published: July 2012

. The synthesis of carbon‐14 labelled acetylcholine (14C‐ACh) from carbon‐14 uniformly labelled glucose (U.L. 14C‐glucose) under different conditions has been studied.
. Increasing KC1 concentration from 4 mm to 31 mm was associated with a large increase in the amount of 14C‐ACh in the medium and a significant decrease in the amount of 14C‐ACh in the tissue. This effect was observed in slices and minces but not in homogenate.
. Increasing KC1 concentration from 4 mm to 31 mm resulted in the release of pre‐formed 14C‐ACh.
. Elevated pre‐incubation levels of ACh in slices incubated in 4 mm KC1 medium was associated with a decrease in the formation of 14C‐ACh.
. These findings are consistent with the hypothesis that the concentration of ACh in the vicinity of the site of synthesis regulates the rate of ACh formation.
The pharmacology of ambenoxan (2‐(3′,6′‐dioxaheptyl)‐aminomethyl‐1: 4‐benzodioxane), a centrally acting muscle relaxant
Authors: SHAPERO M. , SOUTHGATE P. J. 
Published: July 2012

Summary
. The intravenous, subcutaneous and oral toxicity of ambenoxan in mice is reported.
. Ambenoxan is a centrally acting skeletal muscle relaxant shown to be effective in mice, rats, rabbits, dogs and monkeys without loss of the righting reflex.
. It had no peripheral neuromuscular blocking properties.
. Decerebrate rigidity was depressed or abolished in the rabbit.
. The effects of strychnine, leptazol, or tremorine were not antagonized.
. In common with other depressants of the central nervous system, ambenoxan prolonged the sleeping time of hexobarbitone.
. Ambenoxan had no local anaesthetic properties.
. In the anaesthetized cat the drug lowered the blood pressure and reduced the pressor response to adrenaline but not to noradrenaline.
Study of the effects of progesterone therapy on the stilboestrol‐induced sensitivity of isolated uteri of hypophysectomized rats
Authors: KHAN I. , QURESHI Z. , HAQ M. 
Published: July 2012

Summary
. In intact rats progesterone (50 mg/kg) antagonized the effect of stilboestrol (100 μg/kg) on the vaginal smears and the uterine sensitivity. The uterine sensitivity to acetylcholine, oxytocin and 5‐hydroxytryptamine was decreased by 6·8, 64 and 14·8 times, respectively, as compared with uteri removed after stilboestrol injections.
. Progesterone therapy in hypophysectomized rats also antagonized the effect of stilboestrol on the vaginal mucosa and on the uterine sensitivity to drugs. The sensitivity to acetylcholine, oxytocin and 5‐hydroxytryptamine was decreased by 6·2, 50 and 14·5 times, respectively. Similar results were obtained on uteri removed from sham‐hypophysectomized rats.
. On the basis of these results it is suggested that the hypophysis does not play any part in the desensitization of the myometrium to the oxytocic drugs and in the changes found in the vaginal mucosa after progesterone therapy.
The effect of antiadrenaline compounds on acetylcholine responses of frog rectus abdominis muscle
Authors: EDGE N. D. 
Published: July 2012

Summary
. Nine antiadrenaline compounds and ergometrine have been examined for their effect on acetylcholine (ACh)‐induced contractures of the frog isolated rectus abdominis muscle.
. Tolazoline caused potentiation (pP2 = 4·14 at 7 min). Slightly higher concentrations of tolazoline caused antagonism (pA2 = 3·68 at 37 min).
. No potentiation of ACh responses was seen with any of the remaining compounds, which all antagonized ACh responses. Phenoxybenzamine gave the highest, and ergometrine the lowest, pA2 values.
. In the concentrations needed to determine pA2, yohimbine and ergometrine also had other effects on the muscle.
. These results are discussed in the context of previous findings.
The relationship between kidney and urinary kininogenase
Authors: NUSTAD K. 
Published: July 2012

Summary
. Rat kidneys which were perfused with saline contained both kininogenase (KGA) and kininase activity. These activities were separated by gel filtration on a Sephadex G‐100 column. The kininase activity was excluded from the column whereas the KGA activity was retained. Kidney KGA activity was primarily found in the sedimentable fraction of the homogenate.
. The kidney KGA activity was compared with the urinary KGA activity, and the following properties were found to be the same: molecular dimension, pH optimum, effect of inhibitors, and ability to liberate kinins from kininogens.
. A urinary sample collected over 24 h contained about 8 times the KGA activity found in the corresponding kidneys at the end of the collection period. The urine: kidney ratio for alkaline phosphatase was about 0.01.
. The ability of kidney and urinary samples to hydrolyse N‐α‐benzoyl‐l‐arginme ethyl ester (BAEE) at pH 8.5 paralleled the KGA activity.
Dissociation of potentiation of isoprenaline by cocaine from inhibition of uptake in cat spleen
Authors: DAVIDSON W. J. , INNES I. R. 
Published: July 2012

Summary
. Cocaine hydrochloride, 10 μg/ml, potentiated isoprenaline and noradrenaline in isolated spleen strips from normal cats and from cats treated with reserpine 24 h previously.
. Isoprenaline was taken up almost as well as noradrenaline by spleen strips from cats treated with reserpine.
. Cocaine blocked uptake of noradrenaline but did not reduce uptake of isoprenaline. Drug concentrations used in these studies were the same as in potentiation experiments.
. It is concluded that inhibition of uptake is not the mechanism by which cocaine potentiates the effect of isoprenaline on the spleen and might be only a contributory factor in the case of noradrenaline potentiation.
Restoration of tyramine responses by bretylium, BW392C60, bethanidine and monoamine oxidase inhibitors in reserpine‐treated rats
Authors: CLARKE D. E. 
Published: July 2012

Bretylium, BW392C60, bethanidine, nialamide and pheniprazine, but not guanethidine or ouabain, were all capable of restoring the cardiovascular response to tyramine in reserpine pretreated rats anaesthetized with sodium pentobarbitone.
In parallel with their recorded in vitro activity as monoamine oxidase inhibitors, BW392C60 was found to be more potent at restoring the response to tyramine than bretylium or bethanidine.
The restored responses to tyramine were completely blocked by desmethylimipramine or by a combination of phentolamine and propranolol.
The effect of bretylium on the tyramine response was not influenced by bilateral adrenal demedullation, urethane anaesthesia, the dose or duration of the reserpine pretreatment and was not dependent upon the frequency of the tyramine injections.
Bretylium, BW392C60 or bethanidine did not alter the pressor response to intravenous noradrenaline.
Nialamide‐induced restorations of the responses to tyramine were not further enhanced by the administration of bretylium, BW392C60 or bethanidine.
In pithed reserpine‐treated rats the ability of bretylium and BW392C60 to restore the response to tyramine was reduced.
It is concluded that all the drugs which reversed the reserpine‐induced subsensitivity to tyramine were acting as monoamine oxidase inhibitors, thus allowing the intra‐neuronal accumulation of endogenously formed catecholamines. The presence of nerve impulses in the adrenergic fibres of reserpinized rats appears to be an important factor in mediating this effect.
The effects of beta adrenoceptor blocking agents on the membrane potential and spike generation in the smooth muscle of guinea‐pig taenia coli
Authors: DAVIS W. G. 
Published: July 2012

The measurement of changes in spike generation and membrane resistance in the guinea‐pig taenia coli, using the sucrose gap extracellular recording method, has been shown to be a useful way to demonstrate the intrinsic sympathomimetic activity of the beta adrenoceptor blocking agents.
Pronethalol, INPEA, MJ 1999, MJ 1998 and dichloroisoprenaline abolish the spontaneous spike discharge and produce a hyperpolarization of the cell membrane. These sympathomimetic effects were blocked by a mixture of alpha (phentolamine) and beta (propranolol) adrenoceptor blocking agents.
Propranolol reduced the frequency of the spontaneous spike potentials but did not raise the resting membrane potential of the taenia coli.
When the metabolism of the taenia coli was depressed, all the beta adrenoceptor blocking agents produced a depolarization of the cell membrane and sometimes initiated spike potential activity. The depolarization of the cell membrane was antagonized by superfusing the taenia coli with Krebs solution containing phentolamine. The effects of the beta adrenoceptor blocking agents were not antagonized by the presence of atropine.
Experiments performed on the reserpinized taenia coli preparation show that depletion of the stores of catecholamines did not modify the sympathomimetic actions of the beta adrenoceptor blocking agents on the normal or metabolically depressed taenia coli preparation. The sympathomimetic action of the beta blocking agents does not appear to be mediated through the release of catecholamines within the taenia coli.
Vascular resistance in the perfused isolated rat tail
Authors: WADE D. N. , BEILIN L. J. 
Published: July 2012

A constant flow perfusion system using the isolated rat tail has been developed to facilitate the study of resistance vessel behaviour and the action of vasoactive drugs.
Baseline resistance remains stable for several hours and dose response curves to bolus injections of pressor agents are reproducible when dialysed bovine serum albumen is used in the perfusion medium to maintain osmotic pressure.
Noradrenaline, adrenaline, serotonin, vasopressin, angiotensin II, high potassium concentrations and sympathetic nerve stimulation constricted the vascular bed.
Angiotensin I, bradykinin, histamine, acetylcholine and isoprenaline did not alter vascular resistance under baseline conditions.
Maximal sensitivity to noradrenaline occurred at 32° to 34° C. Below 30° C, resting tone increased and the pressor effect of noradrenaline was prolonged.
Low concentrations of (±)‐propranolol in the perfusate enhanced adrenaline and noradrenaline vasoconstriction, high concentration of (±)‐propranolol had a direct pressor effect and did not affect catecholamine responses.
The preparation is a simple and relatively inexpensive adjunct to established methods of studying resistance vessel behaviour under varying experimental conditions.
Acid metabolites of monoamines in avian brain; effects of probenecid and reserpine
Authors: AHTEE LIISA , SHARMAN D. F. , VOGT MARTHE 
Published: July 2012

The concentration of the dopamine (DA) metabolite 3,4‐dihydroxyphenylacetic acid (DOPAC) in the anterior part of the nucleus basalis of pigeon brain was found to be 0.17 ± 0.01 μg/g, which is about one‐fifth of the concentration of homovanillic acid (HVA) in this region. In the chicken, the concentration of HVA in the (entire) nucleus basalis was 0.06 ± 0.006 μg/g, lower than in any other species examined, and giving a ratio of DA to HVA of about 50. The concentration of DOPAC in the 8 day old chick was 0.053 ± 0.002 μg/g.
Probenecid, 200 mg/kg intramuscularly, doubled the content of DOPAC in the nucleus basalis of the pigeon and increased the concentration of HVA in both the pigeon and the chicken by a factor of 4 to 5. These findings demonstrate the existence, in avian brain, of an active transport mechanism for the removal of acidic substances and explain the low concentrations of the acids found in bird brain.
A method is described for the estimation of 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindolylacetic acid (5‐HIAA) in the same tissue sample. Probenecid caused an increase in the 5‐HIAA content but produced no change in the 5‐HT content of the nucleus basalis of pigeon brain.
Reserpine caused a fall in the content of acidic DA metabolites in the nucleus basalis of the pigeon. The effect was more pronounced after raising the concentration of these acids with probenecid.
Treatment of pigeons with pargyline (100 mg/kg 17 hr before decapitation) did not significantly increase the DA content of the nucleus basalis, but it prevented to some extent the loss in DA caused by reserpine.
Pigeons and chickens were sedated by probenecid. The deepest sedation occurred at about the same time as the greatest increase in the acidic amine metabolites in the brain.
Intracisternal injection of HVA in the pigeon and intravenous injection of large amounts of HVA, DOPAC, 5‐HIAA or 3,4‐dimethoxyphenylacetic acid into newly hatched chicks did not produce any sedation or other effects on behaviour. In contrast, injection of sodium γ‐hydroxybutyrate caused paralysis followed by prostration and eye closure.
Estimation of the concentration of HVA in the brain of the young chick after intravenous injection of the acid (100 mg/kg) showed that the concentration was of the same order of magnitude as it is in animals given probenecid; this suggests that the sedation which follows probenecid is not related to the accumulation of acidic amine metabolites.
Properties of cholinoceptive neurones in the medial geniculate nucleus
Authors: TEBĒECIS A. K. 
Published: July 2012

Acetylcholine (ACh), other cholinomimetics, cholinesterase inhibitors and cholinergic antagonists were administered iontophoretically to medial geniculate (MG) neurones and their effects on chemically or neurally evoked responses recorded extracellularly.
Acetylcholine had excitant actions on 45% of the neurones tested. Most of these were of a slow time course. Desensitization to the excitant effects was frequently observed.
Acetylcholine excited 91% of neurones activated antidromically by stimulation of the auditory cortex, 71% of neurones activated synaptically from the auditory cortex, 74% of neurones activated from the inferior colliculus and 100% of geniculo‐cortical relay neurones.
Acetylcholine had depressant effects, which were generally of a rapid time course, on 29% of MG neurones. No desensitization to the depressant effects was observed.
On 4% of neurones, ACh had both excitant and depressant effects. Such “dual” effects were manifested either as an initial excitation followed by a depression, or as a depression followed by an excitation.
Eserine, neostigmine and edrophonium potentiated both excitant and depressant actions of ACh on many cells. Neostigmine and edrophonium occasionally antagonized the effects of ACh.
Atropine, hyoscine, dihydro‐β‐erythroidine, hexamethonium and (+)‐tubocurarine antagonized both excitant and depressant effects of ACh. The muscarinic blocking agents were usually more effective than the nicotinic agents.
Carbamylcholine, acetyl‐β‐methylcholine, nicotine, butyrylcholine, arecoline and pilocarpine had excitant, depressant or no effects on MG neurones. Generally, carbamylcholine was more potent than acetyl‐β‐methylcholine and ACh, which were more potent than nicotine. Butyrylcholine, arecoline and pilocarpine were even less potent, often having no effect.
The cholinomimetics generally had similar effects to those of ACh on the same neurones, but sometimes were quite different. Carbamylcholine, acetyl‐β‐methylcholine and nicotine antagonized the effects of ACh on some neurones.
The results suggest that cholinoceptive receptors on MG neurones are not homogeneous. Although there are possibly some purely muscarinic and purely nicotinic receptors, the majority appear to be of intermediate muscarinic‐nicotinic type. These mediate either excitation or inhibition.
The assay of gastrin using the perfused rat stomach
Authors: SMITH G. M. , LAWRENCE A. J. , COLIN‐JONES D. G. , SCHILD H. O. 
Published: July 2012

A method is described for the bio‐assay of gastric secretagogues using the perfused rat stomach in which the acid output can be readily and accurately quantified.
This technique increases the sensitivity of the perfused rat stomach so that 10–20 ng of synthetic human gastrin I can be detected.
It is possible to assay secretagogues, relative to a standard with fiducial limits of less than ±30%.
The use of this system is illustrated by assays comparing synthetic human gastrin I with pentagastrin, pure hog gastrin and gastrin added to plasma.
An inhibitory action of histamine on the guinea‐pig ileum
Authors: AMBACHE N. , ZAR M. ABOO 
Published: July 2012

In atropinized, plexus‐containing preparations of the longitudinal muscle from the guinea‐pig ileum, in which histamine contractions were abolished by mepyramine or diphenhydramine, an inhibitory action of histamine was revealed on the “tetanic spasms” produced by field stimulation.
The inhibitory action of histamine on the atropine‐resistant tetanic spasms, which are due to the excitation of non‐cholinergic neurones in Auerbach's plexus (Ambache & Freeman, 1968a, b), was reversible. It is specific for the tetanic spasms, because histamine did not reduce contractions elicited by bradykinin, 5‐hydroxytryptamine, prostaglandin E2, nicotine or dimethylphenylpiperazinium.
l‐Histidinol and 2‐mercaptohistamine exerted a considerably weaker inhibitory effect upon the tetanic spasms than histamine. Four other imidazoles tested, l‐histidine, murexine, dihydromurexine and imidazolecarboxylcholine, were ineffective; so was the pyrazole ring isomer of histamine, betazole.
The inhibitory action of histamine persisted after adrenoceptor blockade by phentolamine and pronethalol and after prior reserpinization of the guinea‐pigs.
The inhibitory action of histamine was also obtained after ganglionic paralysis by hexamethonium or dimethylphenylpiperazinium but was antagonized specifically by nicotine.
On atropinized preparations of the longitudinal muscle from the guinea‐pig descending colon histamine exerted, at most, an insignificant inhibitory effect on the tetanic spasms.
Gastrin derivatives investigated for secretory potency and for changes in gastric mucosal histamine formation
Authors: ROSENGREN ELSA , SVENSSON S. E. 
Published: July 2012

Summary
. Acid secretion and rate of histamine formation in the gastric mucosa were determined in rats after injection of hog gastrin II, gastrin pentapeptide and some substituted analogues of the C‐terminal tetrapeptide of gastrin.
. Accelerated mucosal histamine formation was induced by hog gastrin II, gastrin pentapeptide and those analogues which elicited acid secretion, whereas secretorily inactive derivatives did not alter histamine formation.
In vivo studies on histamine catabolism and its inhibition
Authors: REILLY MARGARET A. , SCHAYER R. W. 
Published: July 2012

Summary
. Histamine catabolism in vivo was studied in mice subjected to various forms of pretreatment; tissues from mice killed 2·5 min after intravenous injection of 14C‐histamine were assayed for 14C‐histamine, 14C‐methylhistamine and total 14C.
. Pretreatment of mice with aminoguanidine, an inhibitor of diamine oxidase, strongly increased levels of 14C‐histamine in intestine; pretreatment with aminoguanidine plus a monoamine oxidase inhibitor strongly increased levels of 14C‐methylhistamine in liver. Effects in other tissues are reported and discussed.
. Pretreatment of mice with non‐isotopic methylhistamine increased levels of 14C‐histamine in liver. Methylhistamine is the first known inhibitor of histamine‐methylation in vivo.
. Pretreatment of mice with inhibitors of protein synthesis, drugs which reduce the basal activity of histidine decarboxylase and which block its activation, failed to affect histamine catabolism.
. Pretreatment of mice with endotoxin or with Freund's adjuvant, irritants known to cause activation of histidine decarboxylase, failed to affect histamine catabolism.
. There was no evidence of parallelism between the histamine‐destroying enzymes and the histamine‐forming enzyme, histidine decarboxylase, either in distribution or ability to undergo changes in activity. No support was obtained for the view that histamine‐catabolizing enzymes play a role in the local control of responses to newly formed histamine.
Studies on the blocking action of 2‐(4‐phenyl piperidino) cyclohexanol (AH5183)
Authors: MARSHALL I. G. 
Published: July 2012

Summary
. AH5183 (2‐(4‐phenyl piperidino) cyclohexanol) produced neuromuscular block of slow onset in rapidly stimulated nerve‐skeletal muscle preparations of the rat, chicken and cat.
. The neuromuscular block was not antagonized by neostigmine, tetraethylammonium (TEA) or choline. The rate of onset of transmission failure was enhanced by factors which increase the release of acetylcholine.
. It was concluded that the neuromuscular blocking activity was primarily pre‐junctional in origin, being due either to a non‐competitive action on the choline transport mechanism, or to an intracellular action on acetylcholine metabolism.
. In high doses AH5183 possessed local anaesthetic activity, but this was considered insufficient to bring about the failure of neuromuscular transmission.
. AH5183 also produced a block of sympathetically innervated preparations that was indistinguishable from that produced by an α‐adrenoceptor blocking drug.
Acute effects of a monoamine oxidase inhibitor, tranylcypromine, on thermoregulation in the conscious rabbit
Authors: CRANSTON W. I. , ROSENDORFF C. 
Published: July 2012

Summary
. The effect of a single injection of the monoamine oxidase inhibitor, tranylcypromine, administered intravenously (20 mg/kg) or into the lateral cerebral ventricle (5–10 mg), on hypothalamic and rectal temperature, has been investigated.
. Intravenous tranylcypromine causes a significant rise in body temperature, which is due, at least in part, to cutaneous vasoconstriction; this vasoconstriction is augmented by sympathectomy. It is concluded that this vasoconstrictor effect is not mediated via the central nervous system.
. Intraventricular tranylcypromine caused a transient but significant fall in core temperature. This is interpreted as being compatible with selective augmentation of hypothalamic levels of 5‐hydroxytryptamine.