bluuebunny/crossref_metadata_2025 huggingface dataset:
The time course of action of (—)‐hyoscine after intramuscular injection
Authors: BRAND J. J.
Published: July 2012

Although (–)‐hyoscine has been in clinical use for many years, there is little detailed information concerning the speed of absorption or duration of action of the drug after single intramuscular doses.

The time course of action of the drug was therefore examined using biological methods, and measurements were made of saliva flow, pulse rate, pupil diameter and mental alertness for up to 8 hr after doses of 0.4, 0.2, 0.1 and 0.05 mg of the hydrobromide.

These techniques gave comparable results and peak activity was achieved at 1–2 hr after dose and followed by a gradual decline over the 8 hr period.

The results are compared with those of earlier experiments of a similar kind, and discussed in relation to their bearing on both therapeutics and experimental design.
Displacement from protein binding of sulphormethoxine by phenylbutazone using in vivo dialysis in rats
Authors: McQUEEN E. G.
Published: July 2012

Displacement of the ultra‐long‐acting sulphonamide sulphormethoxine from binding to serum proteins by phenylbutazone has been demonstrated by in vivo dialysis in rats. The technique used involved the introduction of dialysis sacs into the peritoneal cavity. The regression line relating free to total sulphormethoxine was significantly displaced after addition of phenylbutazone to the regime although the mean level of free drug was not significantly raised. No significant effect was observed on the proportion of phenylbutazone in the free form. The range of concentrations employed corresponded to that encountered clinically.

In vitro experiments with comparable concentrations of both drugs confirmed displacement of sulphormethoxine by phenylbutazone. Insignificant displacement of phenylbutazone from binding occurred. These experiments indicated the relationships between the relative affinities of sulphormethoxine and phenylbutazone for serum proteins and the extent to which mutual displacement from binding occurred.
Hypothermia following intraventricular injection of hemicholinium‐3 in rats
Authors: SLATER P.
Published: July 2012

In unanaesthetized rats, a dose of 50 μg of hemicholinium‐3 injected into the cerebral ventricles produced a prolonged hypothermia which was unaffected by the simultaneous administration of choline. This suggests that it was not due to inhibition of acetylcholine synthesis.

An intraperitoneal injection of 50 μg of hemicholinium‐3 also produced hypothermia which, however, was blocked by choline which suggests that it is due to inhibition of acetylcholine synthesis.

Hyoscine and hexamethonium did not block the hypothermia produced by intraventricular hemicholinium‐3, but some antagonism was obtained with phentolamine, imipramine and amphetamine.

When hemicholinium‐3 was administered intraventricularly to rats pretreated with desmethylimipramine, a lethal hyperthermia developed.

It is concluded that no central cholinergic mechanism is involved in the hypothermia of the rat resulting from an intraventricular injection of hemicholinium‐3.
The actions of some cholinomimetic drugs on the isolated taenia of the guinea‐pig caecum
Authors: HOBBIGER F. , MITCHELSON F. , RAND M. J.
Published: July 2012

The actions on the taenia of 4‐(m‐chlorophenylcarbamoyloxy)‐2‐butynyltrimethylammonium chloride (McN‐A‐343), N‐benzyl‐3‐pyrrolidyl acetate methobromide (AHR‐602), tetramethylammonium (TMA) and choline phenyl ether have been examined and compared with the actions of acetylcholine, nicotine and 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP).

Responses of the taenia to these agonists are quantitatively and often qualitatively dependent on the tone of the preparation. A method is described which makes allowance for the effect of tone on heights of contractions.

Acetylcholine, McN‐A‐343 and AHR‐602 produced only contractions; TMA produced contractions or biphasic responses; and choline phenyl ether, nicotine and DMPP produced contractions, relaxations or biphasic responses.

The mode of action of these compounds has been analysed by means of hyoscine, ganglion‐blocking drugs, tetrodotoxin and local anaesthetics.

It is concluded that acetylcholine, McN‐A‐343, AHR‐602, TMA and choline phenyl ether act on muscarinic receptors in the smooth muscle. Choline phenyl ether has an additional action on nicotinic receptors of cholinergic neurones. Nicotine and DMPP act on nicotinic receptors of cholinergic neurones and of inhibitory neurones. An action on the latter is sometimes also seen with TMA and choline phenyl ether.

With nicotine or DMPP, and TMA or choline phenyl ether in the presence of hyoscine, part of the contraction phase of biphasic responses (in which a contraction follows relaxation) is best explained as being triggered by the initial relaxation—that is, as a “rebound contraction”.

None of the compounds tested appeared to exert an atropine‐sensitive action on neurones.

In the presence of hyoscine high concentrations of agonists can act on sites not involved with lower concentrations.

The degree of antagonism obtained with procaine against compounds acting on muscarinic receptors on the smooth muscle varies with the compound tested.
Renal actions of dihydroergocristine and of phentolamine in anaesthetized cats
Authors: LOCKETT MARY F. , WADLEY ROSALIE
Published: July 2012

. Comparison has been made of the effects of dihydroergocristine (DCS) and phentolamine mesylate (phentolamine) on cardiac and respiratory rates, systemic arterial pressure, renal clearances of creatinine (CCr) and of p‐aminohippuric acid (CPAH) and on the secretion of Na and K, in cats under chloralose anaesthesia.

. Phentolamine antagonized vasomotor tone and the pressor effect of circulating noradrenaline to comparable extent. The extent of reduction in urine flow, CCr, CPAH and Na excretion correlated with the fall in mean arterial pressure. Innervated and denervated kidneys responded similarly. Cardiac and respiratory rates rose slightly as arterial pressure fell.

. DCS, 10 to 20 μg/kg per min, did not reduce vasomotor tone, markedly reduced the pressor effect of exogenous noradrenaline, caused bradycardia and respiratory slowing but had little or no effect on renal function.

. DCS, 30 to 40 μg/kg per min, lowered mean arterial pressure by 15–25 mm Hg, decreased CPAH but not CCr, so raising the filtration fraction and caused a small reduction in urine flow and in Na excretion. Innervated and acutely denervated kidneys responded similarly.

. DCS, 30 to 40 μg/kg per min, raised mean arterial pressure, decreased CPAH, urine flow and Na excretion but did not alter CCr in animals pretreated with full α‐adrenergic blocking doses of phentolamine.

. DCS, 30 to 40 μg/kg per min, increased the rate of secretion of sympathetic amines from the adrenal medulla and increased the concentration of renin in renal venous blood.

. Isolated kidneys perfused at constant pressure from pump‐oxygenator circuits and in saline diuresis responded to DCS (15–17 μg/120 ml. blood) by diuresis and natriuresis and by a rise in the rate of secretion of renin. Higher concentrations of DCS (125–250 μg/120 ml.) were without effect on renal function and did not influence renin secretion.

. The renal effects of full α‐adrenergic blocking doses of DCS and of phentolamine were comparable, in the whole animal.

. The evidence indicates that the release of noradrenaline by DCS 30–40 μg/kg per min from nerve terminals supplying the juxtaglomerular apparatus may have caused the enhancement of renin secretion.
Effects of immobilization on rat liver tryptophan pyrrolase and brain 5‐hydroxytryptamine metabolism
Authors: CURZON G. , GREEN A. R.
Published: July 2012

. Rat liver tryptophan pyrrolase increased on immobilization. The concentration of 5‐hydroxyindoleacetic acid in the brain also rose and that of 5‐hydroxytryptamine fell.

. When adrenalectomized rats were immobilized pyrrolase activity did not rise and brain 5‐hydroxytryptamine concentration fell to a lesser extent but the 5‐hydroxyindoleacetic acid concentration rose as in intact animals.

. When intact rats were injected with the pyrrolase inhibitor Allopurinol both the increase of pyrrolase and the fall of 5‐hydroxytryptamine on immobilization were less prominent but the concentration of 5‐hydroxyindoleacetic acid rose as before. Allopurinol did not affect the changes in immobilized adrenalectomized rats.

. Immobilization thus appears to cause (a) decreased brain 5‐hydroxytryptamine synthesis resulting from pyrrolase induction and (b) increased 5‐hydroxytryptamine breakdown by a more direct effect on the brain. Results of experiments on rats injected with lysergic acid diethylamide, and with α‐methyltryptophan or probenecid are consistent with the above interpretation.

. The 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid changes were maximal after 5–6 hours' immobilization and became less on more prolonged immobilization, which suggests regulatory changes.
The release of prostaglandin E1 from the rat phrenic nerve‐diaphragm preparation
Authors: LAITY J. L. H.
Published: July 2012

. The release of prostaglandin E1 from the rat phrenic nerve‐diaphragm preparation during tetanic contraction of the muscle in response to nerve stimulation is reported. Tentative identification of the prostaglandin depended on solvent extraction column and thin‐layer chromatography and parallel biological assay.

. Polar lipid substances were released from the preparation in the absence of nerve stimulation by (+)‐tubocurarine and noradrenaline.

. The output on nerve stimulation was not abolished by (+)‐tubocurarine, hemicholinium, bretylium or phenoxybenzamine added to the bath.

. The possible origin of these prostaglandins is discussed.
Behavioural and somatic effects of bradykinin injected into the cerebral ventricles of unanaesthetized rabbits
Authors: GRAEFF F. G. , PELÁ IRENE R. , E SILVA M. ROCHA
Published: July 2012

. The effects of bradykinin (1–5 μg) injected into the cannulated lateral cerebral ventricles were studied in unanaesthetized rabbits before and after intravenous atropine, diphemanil and morphine.

. The intraventricular injections of bradykinin produced a short‐lasting phase of behavioural excitation with vocalization followed by sedation. The behavioural excitation was associated with desynchronization in the electrocorticogram (e.co.g.), bradycardia and hypotension followed by tachycardia and hypertension. Tachypnoea was also observed. The subsequent phase of sedation was more prolonged and associated with synchronization of the e.co.g. and signs of catalepsy. Intense miosis was present during both phases.

. With repeated intraventricular injections of bradykinin, excitation, miosis, cardiovascular responses and tachypnoea diminished and eventually disappeared but the sedation did not exhibit tachyphylaxis.

. Atropine abolished the e.co.g. desynchronization, vocalization and bradycardia, reduced the duration of the excitatory and sedatory phase, diminished the tachycardia and hypotension, enhanced the hypertension, but did not affect the miosis and tachypnoea.

. Diphemanil affected only the cardiovascular effects produced by intraventricular bradykinin. They were affected in the same way as by atropine.

. Morphine did not affect the excitatory phase, but enhanced the cardiovascular effects produced by intraventricular bradykinin.

. The intraventricular injection of bradykinin (50 μg) caused a reduction in the amount of noradrenaline but not of 5‐hydroxytryptamine (5‐HT) in the brain stem; the amount of dopamine in the caudate nuclei was not affected.

. It is suggested that central cholinergic and adrenergic systems are activated by intraventricular bradykinin.
Effects of opiates and opiate antagonists on the Straub tail reaction in mice
Authors: ACETO M. D. , McKEAN DONNA B. , PEARL J.
Published: July 2012

. Subcutaneous injections of opiates produced the Straub tail reaction in mice. The potencies of the opiates in mice were consistent with previous estimates of the analgesic potencies in animals and in man.

. The potencies of sixteen antagonists in counteracting the reaction were consistent with those previously obtained with the rat tail‐flick test.

. The (–) isomers of four benzomorphan derivatives were much more potent in counteracting the reaction than their (+) isomers and about twice as potent as their racemates. The activity of the isomers seemed to follow Pfeiffer's rule: the lower the effective dose of a drug, the greater the difference in the pharmacological effects of the optical isomers. One of the trans isomers acted like an opiate, while its cis isomer acted like an antagonist.

. Naloxone and nalorphine fulfilled conventional criteria for competitive antagonism, whereas atropine and the (–) and the (+) isomers of pentazocine and of cyclazocine did not do so.

. The Straub tail test seems to be useful for studying structure‐activity relations among opiates and opiate antagonists.
The mode of action of carbon tetrachloride on Fasciola hepatica
Authors: KHALIDI A. , ZAKI SANIHA AMIN
Published: July 2012

. A biliary fistula was prepared in twelve sheep.

. Each animal was given 2 ml. of 14C‐carbon tetrachloride (specific activity 15 mc/m‐mole) and bile collected at 2, 4, 24 and 48 hr.

. Specific activity was measured by liquid scintillation counting before and after each specimen had been heated to 75°C for 10 min to drive off volatile content (carbon tetrachloride).

. Only traces of activity were present in the bile and heating did not alter this.

. There was no difference in the survival times of adult Fasciola hepatica incubated in Hedon Flieg medium with and without 25% bile from non‐medicated sheep, or with carbon tetrachloride in a concentration of 0.03%, but 25% of bile from sheep given 2 ml. of carbon tetrachloride 24 hr before greatly increased lethality in vitro.

. The anthelmintic action of carbon tetrachloride on F. hepatica does not result from a direct action due to excretion in bile of unchanged carbon tetrachloride but of an unidentified toxic element not necessarily derived from the drug but which arises as a result of its administration.
The action of general anaesthetic agents on root responses of the frog isolated spinal cord
Authors: RICHENS A.
Published: July 2012

. The action of volatile and barbiturate general anaesthetic agents on synaptic transmission in the frog isolated spinal cord has been studied by recording ventral root synaptic potentials and spike discharges evoked by volleys in a dorsal root and in the lateral column fibres.

. Some observations on the distribution of the lateral column fibres and the characteristics of the dorsal root potentials have been presented.

. Volatile agents depressed and eventually abolished all components of the ventral root responses. Failure of motoneurone discharge was the result of two factors, a decrease in the slope of the synaptic potential and an elevation of the critical depolarization required to trigger propagated impulses.

. Barbiturate compounds, in contrast, readily abolished polysynaptic components of the ventral root responses, but the short latency discharge produced by lateral column stimulation was potentiated, and was accompanied by a lowering of the firing threshold of motoneurones. The mechanism of this potentiation by barbiturate compounds is discussed.

. It is concluded that volatile agents act predominantly on the initial segment and subsynaptic elements of the motoneurone, whereas barbiturate compounds depress the presynaptic or postsynaptic components of interneuronal synapses.
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

. 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

. 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

. 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

. 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

. 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

. 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

. 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

. 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

. 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.
The effect of catecholamine infusions on myocardial blood flow, metabolic heat production and on general haemodynamics, before and after alprenolol (H56/28), in anaesthetized cats
Authors: PARRATT J. R. , WADSWORTH R. M.
Published: July 2012

. In cats anaesthetized with pentobarbitone sodium, infusions of adrenaline, noradrenaline (0·5 μg/kg per min) and isoprenaline (0·25 μg/kg per min) increased myocardial blood flow, myocardial heat production, left ventricular systolic and end‐diastolic pressures, left ventricular +ve and –ve dp/dt max, and calculated cardiac output, effort and oxygen consumption. These effects (apart from the effect of noradrenaline on left ventricular systolic pressure) were markedly reduced by previous administration of alprenolol (0·5 or 1·0 mg/kg).

. Infusions of adrenaline and noradrenaline increased arterial diastolic blood pressure and isoprenaline reduced it. After alprenolol the effects of adrenaline and noradrenaline were potentiated and that of isoprenaline abolished; in some experiments isoprenaline increased arterial diastolic pressure after alprenolol. Alprenolol did not influence the increases in arterial systolic pressure which followed the administration of adrenaline and noradrenaline.

. Isoprenaline‐induced tachycardia was markedly reduced and adrenaline tachycardia was converted to bradycardia after alprenolol. The bradycardia which occurred during noradrenaline infusions was unaffected.

. After blockade by alprenolol, recovery of the effects of isoprenaline on left ventricular dp/dt and on heart rate occurred more quickly than recovery of the effects on arterial diastolic pressure. This suggests that alprenolol has a greater affinity for β2‐ than for β1‐adrenoceptors.

. Intravenous administration of acetylcholine decreased arterial blood pressure, left ventricular pressure and +ve and –ve dp/dt max. During recovery from these effects there was a marked increase in +ve dp/dt max. which was absent after the administration of alprenolol (0·5 mg/kg). Because this dose of alprenolol is thus able to block the effects of reflex sympathetic cardiac nerve stimulation but does not completely antagonize the effects of exogenous adrenaline on dp/dt, it is suggested that alprenolol may have some adrenergic neurone blocking activity.

. Increases in liver and myocardial blood flow and heat production produced by noradrenaline, adrenaline and isoprenaline were reduced after alprenolol.

. Isoprenaline reduced air‐way resistance and this effect was abolished by alprenolol; increases in air‐way resistance produced by adrenaline and noradrenaline were augmented. All three amines inhibited intestinal smooth muscle contractions in vivo. Only the effect of isoprenaline was reduced by alprenolol.
The vascular responses of the spleen to intravenous infusions of catecholamines, angiotensin and vasopressin in the anaesthetized cat
Authors: GREENWAY C. V. , STARK R. D.
Published: July 2012

. Splenic arterial flow and splenic weight were recorded in cats anaesthetized with sodium pentobarbitone. The responses of the spleen to catecholamines, angiotensin and vasopressin were investigated.

. Catecholamines caused responses mediated by α‐ and β‐adrenoceptors in the arteriolar smooth muscle, but only insignificant β‐adrenoceptor responses could be elicited from the capsular smooth muscle. The difficulties in elucidating the mechanism of action of catecholamines on arteriolar smooth muscle are discussed.

. Angiotensin caused marked vasoconstriction, but contraction of the capsular smooth muscle was less marked. Vasopressin caused vasoconstriction but had no effect on capsular smooth muscle. Thus these peptides constrict the resistance vessels but produce much weaker contraction of the capsule.

. These responses are discussed in relation to the splenic responses to acute haemorrhage.
Coronary vasodilatation following diazepam (Valium)
Authors: ABEL R. M. , REIS R. L. , STAROSCIK R. N.
Published: July 2012

. The effects of diazepam (Valium) on coronary and systemic vascular resistance were studied in anaesthetized dogs on cardiopulmonary bypass under conditions of constant heart rate and aortic pressure.

. Pharmacological doses of diazepam uniformly produced coronary vasodilation lasting 30 min; systemic vascular resistance also decreased, but to a lesser degree.

. When coronary blood flow was maintained constant at physiological levels, diazepam produced no changes in left ventricular contractility, as assessed by peak LV isovolumetric pressure, dp/dt max, force‐velocity, and length‐tension relations, whereas previous experiments had demonstrated a positive inotropic effect in a similar preparation in which coronary blood flow was responsive to alterations in coronary vascular resistance.

. In five dogs, complete separation of the coronary and systemic circulations was accomplished by a double pump‐oxygenator system; direct intracoronary administration of diazepam produced coronary vasodilatation, but coronary pressure and flow were not altered by administration of diazepam to the systemic circulation.

. It is concluded that diazepam augments myocardial contractility by increasing coronary blood flow. This relationship is independent of extracardiac humoral mechanisms, and appears to require the delivery of diazepam to the coronary circulation.
The effect of Arvin on reticulo‐endothelial activity in rabbits
Authors: ASHFORD A. , BUNN D. R. G.
Published: July 2012

. Arvin stimulated the reticulo‐endothelial uptake of colloidal carbon in rabbits. The onset of effect after intravenous administration was immediate and the minimum stimulant dose by this route was very low—0·05 unit/kg (0·1 μg protein/kg).

. Carbon opsonized in vitro with serum taken 4 h after an intravenous injection of Arvin was cleared more rapidly than carbon treated with control serum. Serum collected 10 min after Arvin did not promote carbon uptake.

. Reticulo‐endothelial block with Thorotrast or excess carbon did not prevent the stimulant effect of Arvin but prevented the stimulant effect of opsonization with 4 h serum.

. The reticulo‐endothelial stimulant effect of Arvin appears to be unrelated to its coagulant action on fibrinogen. The mechanism may involve a direct action on phagocytic cells and an effect on colloidal particles via serum opsonins.
The effects of caerulein on insulin secretion in anaesthetized dogs
Authors: BERTACCINI G. , DE CARO G. , MELCHIORRI P.
Published: July 2012

. Insulin concentration changes in pancreatico‐duodenal venous plasma were studied in anaesthetized dogs injected with caerulein.

. Rises in insulin concentration were elicited by rapid intravenous injection of caerulein, as well as by intravenous infusion. Threshold doses were 10 ng/kg and 0·5–1 (ng/kg)/min respectively.

. At the highest dose used (500 ng/kg by rapid intravenous injection and (25 ng/kg)/min by intravenous infusion) the increase in immuno‐reactive insulin release was approximately 7 to 9 times the base levels.

. Adrenalectomy potentiated the effects of intravenous infusion of caerulein.

. On a molar basis, caerulein was 2–3 times as active as pancreozymin.

. It is concluded that caerulein is a potent stimulant of pancreatic islets in the dog and that it may be considered as a model peptide, capable of being substituted for pancreozymin in any experiment.

. The mechanism of the insulin stimulating effect of caerulein is discussed. The possibility of a direct “β‐cytotropic” effect of the peptide is suggested.
Effects of morphine and pentobarbitone on acetylcholine synthesis by rat cerebral cortex
Authors: SHARKAWI M.
Published: July 2012

. The synthesis of carbon‐14‐labelled acetylcholine (14C‐ACh) from carbon‐14 uniformly labelled glucose (U‐14C‐D‐glucose) under different conditions was studied.

. The ability of cerebral cortex slices and minces from morphine‐treated and pentobarbitone‐treated rats incubated in 4 mm K+ medium to form 14C‐ACh was markedly reduced as compared with those from control animals.

. The ability of slices from drug‐treated and control animals incubated in 31 mm K+ medium to form 14C‐ACh was similar.

. Cerebral cortex homogenates from both groups of animals in either 4 or 31 mm K+ medium formed similar amounts of 14C‐ACh.

. These findings add further support to the hypothesis that the concentration of ACh at the site of synthesis governs the rate of formation of the neurotransmitter.