bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of prostaglandins E1 and E2 on human, guinea‐pig and rat isolated small intestine
Authors: BENNETT A. , ELEY K. G. , SCHOLES G. B.
Published: July 2012

. Prostaglandins E1 and E2 contracted the longitudinal muscle of human, guinea‐pig and rat isolated ileum.

. The site of action varied with the species. In the rat and in some strips of human tissue prostaglandin appeared to have only a direct action on or in the muscle cells. In the other strips of human tissue and in guinea‐pig ileum the prostaglandins seemed to stimulate both the intrinsic cholinergic nerves and the muscle cells.

. In contrast to the longitudinal muscle, the circular muscle of human, guinea‐pig and rat isolated ileum was usually inhibited by prostaglandin, apparently by an action directly on the muscle cells.

. Prostaglandins may play a part in the control of intestinal motility.
Behavioural and biochemical effects of 2‐(2,6‐dichlorophenylamino)‐2‐imidazoline hydrochloride (St 155) on the central nervous system
Authors: LAVERTY R. , TAYLOR K. M.
Published: July 2012

St 155 (2‐(2,6‐dichlorophenylamino)‐2‐imidazoline hydrochloride) (0.1–2.5 mg/kg subcutaneously) in rats prolonged chloral hydrate sleeping time, inhibited exploratory activity, reduced rotarod performance and pain‐induced aggression; in rats and guinea‐pigs conditioned avoidance behaviour was inhibited.

In most experiments St 155 was 5–7 times more potent than chlorpromazine on a weight basis. In white rats St 155 and chlorpromazine were equi‐effective in inhibiting conditioned avoidance behaviour. St 155 was relatively less active than chlorpromazine in lowering body temperature.

Chronic treatment with St 155 resulted in a reduction of its hypotensive and sedative effects and caused irritability and spontaneous episodes of severe fighting in white rats.

St 155, at doses causing similar conditioned avoidance response inhibition, produced a significant increase in noradrenaline concentration in all brain regions except the striate. Radioisotope studies indicate an increase in noradrenaline storage without significant changes in metabolism.
The pharmacology of sheep tracheobronchial muscle: a relaxant effect of histamine on the isolated bronchi
Authors: EYRE P.
Published: July 2012

Histamine contracted the tracheal and major bronchial muscles of sheep and relaxed the muscles of the lesser bronchi and bronchioles.

The stimulant action of histamine on the trachea was antagonized by mepyramine, whereas the relaxant effect on the bronchial tree was not.

5‐Hydroxytryptamine contracted the musculature from all parts of the respiratory tract—an effect which was specifically antagonized by both methy‐sergide and atropine.

Acetylcholine contracted all sheep tracheobronchial muscle and isoprenaline relaxed it.

Bradykinin had a very weak stimulant action.

It is concluded that histamine relaxes sheep bronchi by a direct excitation of histamine‐sensitive receptors which are not blocked by mepyramine. No indirect components through autonomic nervous elements or by way of catecholamine release were evident. 5‐Hydroxytryptamine seemed to have a dual mode of action in contracting sheep tracheobronchial muscle (a) directly on its own receptors and (b) indirectly through parasympathetic components.
Blockade or reversal of the contraction induced by calcium and adrenaline in depolarized arterial smooth muscle
Authors: GODFRAIND T. , KABA A.
Published: July 2012

Mesenteric arteries immersed in a depolarizing solution contract in the presence of calcium. These contractions are proportional to the calcium concentration and are reversible.

Mesenteric arteries immersed in a calcium‐free depolarizing solution contract in the presence of adrenaline. Under the experimental conditions reported here, this response develops only about one‐third of the contractile tension developed in polarizing solution (modified Krebs bicarbonate).

Cinnarizine and ohlorpromazine inhibit the contractile response to calcium and induce relaxation of depolarized muscle previously contracted by calcium; cinnarizine was 4 times more potent than chlorpromazine in such activity.

Chlorpromazine inhibits the response to adrenaline in both polarizing and calcium‐free depolarizing solutions, whereas cinnarizine inhibits the response in polarizing solution but not that in calcium‐free depolarizing solution.

The significance of these results is discussed.
Mechanism of cocaine potentiation of responses to amines
Authors: KALSNER S. , NICKERSON M.
Published: July 2012

Effects of cocaine on the magnitude of responses to several biologically active amines and on their rates of inactivation were studied in strips of rabbit thoracic aorta in vitro.

Although cocaine both potentiated responses to noradrenaline, adrenaline and phenylephrine and slowed their inactivation, the correlation between these two parameters under various experimental conditions was poor, and in all cases the delay in intrinsic inactivation was inadequate to account for the observed potentiation.

Potentiation of responses to noradrenaline by cocaine was little decreased in strips stored at 6° C for up to 10 days, although the response to low doses of tyramine was abolished much earlier. Similarly, cocaine clearly potentiated responses to noradrenaline for at least 28 hr at 37° C, at which time responses to noradrenaline alone were markedly decreased.

Cocaine potentiated responses to phenylephrine as well after 60 as after 10 min exposure to the amine in strips in which all intra‐neuronal disposition of this amine had been eliminated by treatment with reserpine and iproniazid.

Cocaine effectively potentiated responses to histamine, but had only a slight and variable effect on those to 5‐hydroxytryptamine (5‐HT). It did not alter the tissue inactivation of histamine, but did significantly slow the inactivation of 5‐HT.

Procaine slowed amine inactivation in the same way and to the same extent as did cocaine, but did not potentiate responses or affect the potentiation produced by cocaine added in its presence.

Cocaine potentiated responses to methoxamine to approximately the same degree as it did those to noradrenaline, although studies by the oil immersion technique clearly demonstrated that the aortic strips were entirely incapable of inactivating methoxamine.

The observations reported and discussed are incompatible with the hypothesis that cocaine potentiates responses to sympathomimetic amines because it prevents their inactivation by nerve uptake and storage and thus diverts larger amounts of agonist to tissue receptors. It is concluded that potentiation and inhibition of amine inactivation reflect two largely independent actions of cocaine in this vascular smooth muscle preparation, and probably in other organs, and that potentiation is a generally unreliable criterion of the blockade of processes inactivating sympathomimetic amines or of the importance of these processes in terminating the action of the amines.
The effects of hyoscine and anticholinesterases on cholinergic transmission to the smooth muscle cells of the avian gizzard
Authors: BENNETT T.
Published: July 2012

. Intracellular recordings were made from smooth muscle cells of the pigeon and chick gizzards. Hyoscine (10−6 g/ml.) blocked, within 2 min, the excitatory junction potentials (E.J.P.s) evoked by transmural stimulation. As the amplitudes of E.J.P.s decreased, their durations also decreased. Hyoscine had no effect on the inhibitory junction potentials (I.J.P.s) evoked by transmural stimulation.

. Initially, physostigmine or neostigmine (10−7 − 5 × 10−6 g/ml.) caused a marked increase in the amplitudes of E.J.P.s, without affecting their time courses. Sometimes, anticholinesterases caused a single stimulus to evoke multiple E.J.P.s.

. After several minutes in the presence of high concentrations (10−6 − 5 × 10−6 g/ml.) of anticholinesterases the muscle cells were depolarized by about 15–20 mV, and thus the amplitudes of I.J.P.s evoked by transmural stimulation were larger than under control conditions. E.J.P.s summed at much lower stimulation frequencies than normal, an observation which indicated that high concentrations of anticholinesterases increased the durations of the E.J.P.S. Repetitive stimulation evoked a membrane depolarization which persisted for as long as 10 sec after stimulation was stopped.

. These results are discussed in terms of the action of the drugs at the nerve‐smooth muscle junction and on ganglion cells in the myenteric plexus.
Histamine formation in rat gastric mucosa and lung after injecting reserpine or adrenaline
Authors: ROSENGREN ELSA , SVENSSON S. E.
Published: July 2012

. In rats the effect of reserpine, adrenaline and gastrin on the histamine forming capacity (HFC) of gastric mucosa and lung was examined.

. Intraperitoneal reserpine as well as subcutaneous adrenaline produced a great increase in HFC of gastric mucosa but a great decrease in HFC of lung. After reserpine the HFC of lung was almost abolished.

. As the HFC changes produced by reserpine occurred also after demedullation of the suprarenale—the changes in the mucosa were in fact accentuated—release of the medullary hormones by the reserpine does not account for these changes.

. Subcutaneous gastrin caused a great increase in HFC of the gastric mucosa but did not affect the HFC in lung.

. The possible role of release of gastrin and corticosteroids for the reserpine‐induced HFC changes is discussed because it is known that reserpine releases gastrin and corticosteroids and that cortisone produces HFC changes in gastric mucosa and lung.
The action of caerulein on pancreatic secretion of the dog and biliary secretion of the dog and the rat
Authors: BERTACCINI G. , DE CARO G. , ENDEAN R. , ERSPAMER V. , IMPICCIATORE M.
Published: July 2012

. Caerulein displayed a potent stimulant action on pancreatic secretion in the dog. Threshold doses were 1–5 ng/kg by rapid intravenous injection, 0.25–1 ng/kg per min by intravenous infusion and 50–100 ng/kg by subcutaneous injection. There was a conspicuous increase not only in the volume flow of pancreatic juice but also in the output of solid constituents of the juice and of amylase. However, continuous stimulation of pancreatic secretion by intravenous infusion of caerulein resulted in a progressive reduction of the amylase concentration and still more of the dry residue content of pancreatic juice. The bicarbonate concentration in pancreatic juice produced by caerulein was similar to that observed in juice secreted following pancreozymin administration or following other stimuli causing the same rate of flow of pancreatic juice.

. On a molar basis, caerulein was 25–30 times as active as human gastrin I and 3–6 times as active as cholecystokinin‐pancreozymin. The presence in the molecule of caerulein of a sulphated tyrosyl residue at position 4 of the decapeptide (position 7 starting from the C‐terminus) was a necessary prerequisite for the manifestation of the cholecystokinin‐pancreozymin‐like actions of caerulein. The C‐terminal heptapeptide of caerulein retained much of the activity of the intact caerulein molecule.

. At high dose levels (50–200 ng/kg in the dog, 1 μg/kg in the rat, by rapid intravenous injection) caerulein stimulated the flow of hepatic bile in the dog and the rat. The dry residue of the bile and the cholesterol concentration were appreciably greater in rats treated with caerulein than in control rats.

. The activity spectrum of caerulein was identical with that of cholecystokinin‐pancreozymin. This is readily explained on the basis of the almost identical structure of the C‐terminal octapeptide of the two peptides.

. Caerulein and some caerulein‐like peptides may be considered as model peptides, capable of being substituted for cholecystokinin‐pancreozymin in all the possible experimental and clinical uses of the duodenal hormone, with the important advantage that they are more easily available.

. The question is raised whether cholecystokinin‐pancreozymin obtained from the duodenum by acid extraction is the authentic hormone or rather a carrier polypeptide from which a smaller active peptide may be set free, when needed, into the circulation.
Effects of nicotine and tobacco smoke on the electrical activity of the cerebral cortex and olfactory bulb
Authors: HALL G. H.
Published: July 2012

. Effects of nicotine, cigarette smoke and carbon monoxide have been compared in the cat encéphale isolé preparation, exhibiting a synchronized electrocorticogram (ECoG) and behavioural sleep.

. 2 ml samples of smoke, containing approximately 7 μg nicotine (approximately 2 μg nicotine/kg for a 3 kg cat), introduced into the lungs at 30 s intervals from a smoking simulator, caused desynchronization of the ECoG and behavioural arousal.

. Effects of smoke were matched in the same experiments by intravenous injections of nicotine, 2 μg/kg every 30 s.

. The use of specific nicotine antagonists, for example mecamylamine, and filters for removing nicotine, indicated the presence in smoke of other agents capable of exerting a pharmacological response.

. Cigarette smoke contains approximately 5·0% carbon monoxide. Introduced into the lungs of cats pretreated with mecamylamine (2 mg/kg), 2 ml samples of 5% carbon monoxide caused changes in the ECoG similar to those caused by smoke.

. Effects of nicotine or smoke were not modified by pretreatment with chlorpromazine (2·0–4·0 mg/kg). Atropine (0·3 mg/kg), however, prevented the cortical activation, but not the behavioural arousal.

. 2 ml samples of smoke applied to the nostrils caused the occurrence in the olfactory bulb of a discharge or burst of “induced” waves. This discharge was sometimes accompanied by a transient period of cortical activation.

. These studies demonstrate that in cats, nicotine is the principal pharmacological constituent of tobacco smoke as far as effects on the central nervous system are concerned, although other constituents of smoke may play a contributory role.
Effect of drugs used in psychoses on cerebral dopamine metabolism
Authors: O'KEEFFE RUTH , SHARMAN D. F. , VOGT MARTHE
Published: July 2012

. Chlorpromazine 15 mg/kg, given daily to cats for 2 weeks, produced a rise in homovanillic acid (HVA) content of the caudate nucleus, whereas the same dose of thioridazine lacked this effect. Of these two drugs, only chlorpromazine causes a high incidence of drug‐induced Parkinsonism in man.

. In the mouse, chlorpromazine, thioridazine and haloperidol increased striatal concentrations of HVA and accelerated the disappearance of dopamine (DA) after inhibition of catecholamine synthesis with α‐methyltyrosine. Low doses of the three compounds increased, whereas high doses reduced, the concentration of DA in the striatum. In their effects on the DA metabolism of the mouse, chlorpromazine and thioridazine had the same potency, but haloperidol was between 10 and 100 times more active than the other two drugs. In producing hypothermia and sedation, the three compounds were equiactive.

. Oxypertine, another drug apt to produce Parkinsonism in man, caused a severe reduction in striatal DA and hypothalamic noradrenaline (NA). Though the clinical signs produced in the mouse were indistinguishable from those seen after the same dose of chlorpromazine, the biochemical changes in the brain were thus quite different.

. Though all the drugs used caused temporary motor disabilities in animals, these bore no resemblance to human Parkinsonism, even when treatment was continued for 7 weeks or more as it was in cats and monkeys. The latter were treated with chlorpromazine 7·5 mg/kg daily, a dose chosen to avoid loss of weight and which may have been too small to produce toxic side‐effects. It caused no changes in striatal DA turnover.

. Even at the high dose of 50 mg/kg, phenoxybenzamine did not increase DA turnover in mouse brain, but it sedated the mice as did the tranquillizers.

. Atropine sulphate, 25 mg/kg, reduced the HVA content of mouse striatum and partially antagonized the rise in HVA produced by phenothiazines. The effect was surmountable. Possible modes of action of atropine are discussed.

. At present we know of two types of biochemical changes which may occur in the brain of animals after treatment with drugs apt to cause Parkinsonism in man: a loss of cerebral catecholamines, as seen after reserpine or oxypertine, or an increase in turnover of DA as after phenothiazines and butyrophenones.
The effect of parachlorophenylalanine on social interaction of male rats
Authors: SHILLITO ELIZABETH E.
Published: July 2012

. Juvenile male rats treated with parachlorophenylalanine showed hair loss round the head and neck extending down the chest and abdomen.

. Treated isolated rats did not have this loss of hair, while untreated animals living in the same cage as treated rats lost their hair. The loss therefore seems to be caused by increased social behaviour. This consists of a greater frequency of chasing each other, rolling over and social grooming.

. Adult male rats show an increase in mounting after treatment with parachlorophenylalanine, and this change in behaviour was counteracted by treatment with 5‐hydroxytryptophan.

. It is concluded that 5‐hydroxytryptamine inhibits sexual behaviour in male rats. The increase in social interaction seen in juvenile rats may be the behavioural precursor of adult sexual behaviour.

. Atropine 2·5 mg/kg blocked all forms of social interaction in adult male rats, although other activity was not altered.
The effects of carbon disulphide exposure on brain catecholamines in rats
Authors: MAGOS L. , JARVIS J. A. E.
Published: July 2012

. Rats exposed to 2.0 mg/l. carbon disulphide (CS2) in the inspired air for 2 days, 4 h a day, showed a 13% decrease in their brain noradrenaline concentration and a 16% increase in their brain dopamine concentration.

. After exposure for 5 or 10 days there was a further decrease in the concentration of noradrenaline in the brain, but brain dopamine returned to the control level.

. In animals treated intraperitoneally with 2.0 mg/kg reserpine and exposed 2 and 3 days later to 2.0 mg/1. CS2 for 4 h per day, the brain dopamine concentration showed a 77% increase compared with the unexposed reserpinized animals, but the noradrenaline concentration remained unchanged.

. The dopamine concentrations in the adrenals after 10 days' exposure to 2.0 mg/1. CS2 were 67% to 100% higher than in the control animals. In reserpinized rats, 2 days' exposure to CS2 nearly trebled the dopamine content of adrenals.

. Exposure to CS2 had no effect on the tyrosine concentration in the brain, and there was no change in the brain monoamine oxidase (MAO) activity. Tyrosine in the brain showed a 30 to 96% increase in concentration and MAO activity, using kynuramine as substrate, showed an approximately 5 % increase 0.5 to 2 h after the subcutaneous administration of 500 mg/kg sodium diethyldithiocarbamate.

. CS2 at 10−2m or lower concentrations had no inhibitory effect on the brain MAO activity in vitro. Diethyldithiocarbamate inhibited MAO at 10−2m, but not at 10−3m or lower concentrations.
The effect of reserpine treatment and decentralization on the ion distribution in the vas deferens of the guinea‐pig
Authors: WESTFALL D. P. , Burn J. H.
Published: July 2012

. The ion distribution in the vas deferens of the guinea‐pig was determined following reserpine treatment and decentralization, procedures known to increase the sensitivity of this muscle to drug stimulation.

. There were no significant changes in the estimated intracellular ion concentrations following the two procedures. The half‐times of 42K and 36C1 effluxes were also unaltered.

. As far as ion content is concerned there is no basis for suggesting an altered resting membrane potential in supersensitive smooth muscle.
1‐Isopropylamino‐3‐(4‐indanoxy)‐2‐propanol HCl: a potent β‐adrenoceptor antagonist
Authors: LEVY B. , WASSERMAN M.
Published: July 2012

. The β‐adrenoceptor blocking activity of 1‐Isopropylamino‐3‐(4‐indanoxy)‐2‐propanol HC1 (USVC 6524) was determined in the anaesthetized dog, the isolated rat uterus and the isolated guinea‐pig tracheal strip.

. USVC 6524 inhibited the positive inotropic, positive chronotropic and vasodilator responses to isoprenaline in the dog in a dose of 10 μg/kg and higher. On the basis of comparative pA2 values, USVC 6524 is approximately 10 times more potent as a β‐adrenoceptor antagonist than propranolol.

. Cardiac depressant effects produced by USVC 6524 were relatively mild and occurred only after the onset of a strong β‐adrenoceptor blockade.

. USVC 6524 also blocked β‐adrenoceptors in the isolated rat uterus and guinea‐pig tracheal spiral strip.
Evidence for separate receptors for melanophore stimulating hormone and catecholamine regulation of cyclic AMP in the control of melanophore responses
Authors: GOLDMAN J. M. , HADLEY M. E.
Published: July 2012

. Skins of the lizard Anolis carolinensis darken in vitro in response to melanophore stimulating hormone (MSH), a peptide hormone, as well as to catecholamines. These hormones darken Anolis skins by dispersing the subcellular organelle, the melanosome, out into the dendritic processes of the dermal melanophores.

. Dibutyryl cyclic AMP and methylxanthines also darken skins. In addition, methylxanthines are synergistic with both catecholamines and MSH in causing skin darkening. These data suggest that the dispersion of melanosomes within melanophores in response to both MSH and catecholamines is mediated by cyclic AMP.

. α‐Adrenoceptor blocking agents inhibit MSH‐induced darkening but potentiate catecholamine‐induced darkening. β‐Adrenoceptor blocking agents, in contrast, inhibit catecholamine‐induced darkening but have no effect on MSH‐induced darkening. This selective blockade of one receptor while the functional integrity of the other receptor is maintained suggests that MSH and catecholamines increase cyclic AMP levels through different receptors.

. Catecholamines exert their action through β‐adrenoceptors; MSH darkens skins through what appears to be a component of the β‐adrenoceptor. β‐Adrenoceptor stimulation may stimulate adenyl cyclase to increase cyclic AMP levels whereas MSH may inhibit cyclic AMP phosphodiesterase thereby preventing cyclic AMP breakdown.
Effects of chronic administration of nicotine on storage and synthesis of noradrenaline in rat brain
Authors: BHAGAT B.
Published: July 2012

Chronic administration of nicotine (0.5 mg/kg, subcutaneously four times a day, 5 days a week, for 6 weeks) did not affect the growth rate and water intake in rats. In these animals food intake was normal for the first 5 weeks, but was significantly increased during the sixth week of treatment.

Nicotine administration increased the blood pressure of rats from 120 mm Hg to 151 mm Hg.

The concentrations of endogenous noradrenaline, dopamine, 5‐hydroxytryptamine and acetylcholine in the brain remained unaltered. However, chronic treatment with nicotine increased the turnover rate of noradrenaline. Initial accumulation of 3H‐noradrenaline was also significantly increased.

It is concluded from these studies that changes in the turnover of cerebral noradrenaline caused by chronic administration rather than changes in the concentration of noradrenaline may be an important factor in nicotine‐induced behavioural changes.
Mephenesin, methocarbamol, chlordiazepoxide and diazepam: actions on spinal reflexes and ventral root potentials
Authors: CRANKSHAW D. P. , RAPER C.
Published: July 2012

Dose levels of mephenesin, methocarbamol, chlordiazepoxide and diazepam which abolished polysynaptic reflex contractions had no effect on monosynaptic knee‐jerk reflexes in chloralose anaesthetized cats.

Ventral root potentials were recorded following stimulation of the corresponding dorsal root (L7 or S1), and the areas of the mono‐ and polysynaptic components were measured by planimetry.

Dose levels of the drugs which abolished polysynaptic reflex contractions reduced the areas of the polysynaptic component of the ventral root potentials by about 50%. Mephenesin and methocarbamol reduced the area of the monosynaptic component to a similar extent. Chlordiazepoxide was less potent in this respect while diazepam was without effect at this dose level.

Linear regression lines were calculated for the reduction in the mono‐ and polysynaptic components of ventral root potentials with increasing doses of each of the four drugs. With methocarbamol and mephenesin the lines were parallel and coincident. With chlordiazepoxide and diazepam they were parallel but not coincident. Large doses of diazepam were required to reduce the area of the monosynaptic component, this drug being the only one of the four tested to have a differential action on the two components which was statistically significant.

The results are discussed in terms of depressant actions of the drugs on α‐motorneurones, effects of the drugs at higher centres concerned with motor function, and the lack of evidence that spinal interneurones represent a specific site of action for centrally acting skeletal muscle relaxants.
Presence of caerulein in extracts of the skin of Leptodactylus pentadactylus labyrinthicus and of Xenopus laevis
Authors: ANASTASI A. , BERTACCINI G. , CEI J. M. , DE CARO G. , ERSPAMER V. , IMPICCIATORE M. , ROSEGHINI M.
Published: July 2012

The South American amphibian Leptodactylus pentadactylus labyrinthicus and the South African amphibian Xenopus laevis contain in their skin a polypeptide indistinguishable from caerulein prepared from the Australian amphibian Hyla caerulea.

The caerulein content of different batches of Leptodactylus pentadactylus labyrinthicus skins varies from 10 to 500–600 μg/g tissue. Drying of the skin causes either a moderate decrease or a slight increase in the caerulein content. Methanol extraction gives considerably higher yields of caerulein than acetone extraction.

Caerulein or caerulein‐like polypeptides also occur in the skin of several other species of Leptodactylus together with 5‐hydroxyindole alkylamines and imidazole alkylamines. Yet other species of Leptodactylus lack caerulein‐like polypeptides and 5‐hydroxyindole alkylamines.

It is suggested that caerulein and caerulein‐like polypeptides may have some function either in the regulation of secretory processes of the skin or in the exchange of water and electrolytes through the skin, or in both.
The effect of isoprenaline on adrenoceptors in human saphenous vein
Authors: COUPAR I. M.
Published: July 2012

The order of potency of sympathomimetic amines in causing contraction of strips of human saphenous vein was (−)‐adrenaline>(−)‐noradrenaline>(−)‐phenylephrine>(±)‐isoprenaline.

The competitive α‐adrenoceptor blocking drugs tolazoline, phentolamine, and thymoxamine and the irreversible blocking drug phenoxybenzamine all blocked noradrenaline and isoprenaline contractions.

Contractions produced by 5‐hydroxytryptamine were also blocked by phentolamine and thymoxamine. Fenfluramine‐induced contractions were not blocked by thymoxamine or phenoxybenzamine.

ED50 contracting doses of isoprenaline did not cause consistent relaxation of noradrenaline‐contracted strips.

It is concluded that human saphenous vein contains a dominant population of α‐adrenoceptors which can be stimulated by high doses of isoprenaline, but the occurrence of β‐adrenoceptors mediating relaxation is rare.
The Schultz‐Dale response of the longitudinal muscle strip preparation of guinea‐pig ileum
Authors: DALE M. MAUREEN , ZILLETTI LUCILLA
Published: July 2012

The mast‐cell distribution in the various layers of the ileum has been described.

Histamine‐content, anaphylactic histamine‐release and the anaphylactic dose‐response curve of the full‐thickness ileum and of the longitudinal muscle strip have been measured and compared.

Tetrodotoxin 10−7 g/ml had no obvious effect on the anaphylactic dose‐response curve of either preparation. This suggests that the plexus is not of any great importance in the Schultz‐Dale reaction.

Exposure of the longitudinal muscle strip to octylamine 10−3 g/ml for 1 min reduced the mast cell content by 95–100%. After this treatment the dose‐response curve to antigen was eliminated, although the muscle still responded to small doses of histamine and to anaphylactic mediators. Pre‐treatment of antibody with octylamine did not impair passive sensitization and subsequent response to antigenic challenge. This suggests that the classical Schultz‐Dale reaction in the strip is mediated mainly by mast cells, and possibly other cells, and is probably not due to a direct effect of the antigen‐antibody reaction on the smooth muscle.

The typical three‐phase anaphylactic response (quick contraction, quick relaxation, slow contraction) of full‐thickness ileum is discussed and compared with the predominantly two‐phase response of the longitudinal muscle strip. No evidence was found for the release of a relaxation‐factor. It is suggested that the initial fast phase may be due to mediators released from mast cells among the longitudinal muscle fibres, and the sustained contraction to a second wave of mediators reaching the longitudinal muscle from deeper layers of the ileum.
Comparison of the effects of propranolol and MJ 1999 on cardiac β‐adrenoceptors in man
Authors: EKUE J. M. KOFI , LOWE D. C. , SHANKS R. G.
Published: July 2012

. Propranolol, a β‐adrenoceptor blocking drug with local anaesthetic and a direct myocardial depressant action, and MJ 1999, a β‐adrenoceptor blocking drug which has no local anaesthetic or intrinsic sympathomimetic action, were compared for β‐adrenoceptor blocking activity in man.

. Propranolol was 2·67 times more active than MJ 1999 in reducing by 50% the tachycardia produced by the intravenous infusion of isoprenaline in healthy volunteers.

. Propranolol and MJ 1999 intravenously both reduced resting heart rate in the standing position and an exercise tachycardia, but there was no qualitative or quantitative difference between them.

. On oral administration, both propranolol and MJ 1999 reduced resting heart rate and an exercise induced tachycardia; propranolol was only slightly more active than MJ 1999.

. In patients with thyrotoxicosis propranolol was about twice as active as MJ 1999 in reducing the heart rate.
Comparison of the inotropic response to glucagon, ouabain and noradrenaline
Authors: SPILKER B.
Published: July 2012

. The inotropic activity of glucagon was compared with catecholamines and cardiac glycosides by in vitro procedures which were able to differentiate between the activities of the latter two groups.

. The frequency‐force curve for glucagon resembled that of noradrenaline at low stimulation frequencies (1 and 2/min) and that of ouabain at more rapid frequencies of stimulation.

. Noradrenaline and adrenaline increased the amplitude of contraction of cat papillary muscles and markedly shortened the time to reach peak tension. Ouabain and glucagon increased tension without any change in the time to peak tension.

. Noradrenaline caused a rapid onset and rate of rise of contraction of cat aortic strips, whereas the response to ouabain was slow in onset and rate of development. Glucagon had no effect on this preparation, even at high concentrations.

. Manganese ions caused a shift of the dose‐response curve to ouabain and glucagon, but not to noradrenaline or calcium. In 0·5 mm Ca media, the response to ouabain was abolished and the curve to noradrenaline shifted.

. When glucagon was added to an atrial preparation, the time to the initial increase in tension and the time to maximal tension was intermediate between that necessary for noradrenaline and that necessary for cardiac glycosides.

. Propranolol blocked the inotropic response to noradrenaline, but not to either ouabain or glucagon.

. A relative measure of contraction‐dependency was described. Cardiac glycosides exhibited a greater degree of contraction‐dependency than either noradrenaline or glucagon.

. Adrenaline elevated the depressed plateau of the action potential from calf and sheep Purkinje fibres, but ouabain and glucagon were without effect.

. Electrophysiological measurements demonstrated that moderate concentrations of glucagon exerted only a small effect in prolonging atrial and ventricular action potentials.

. Several pharmacological blocking drugs and other inotropic agents did not potentiate or block the inotropic response to glucagon. Reserpine pretreatment increased the response to glucagon.

. It was concluded that glucagon has its own spectrum of inotropic activity and does not completely mimic the effects of either ouabain or noradrenaline.
Influence of pH on the inhibitory action of local anaesthetics on smooth muscle contraction
Authors: ANTONIO A. , ROCHA E SILVA M. , YASHUDA Y.
Published: July 2012

. The guinea‐pig isolated ileum kept in a calcium‐free depolarizing solution contracts when calcium is added; the responses are proportional to the concentration of calcium and are reversed by washing.

. The contractions elicited by calcium are inhibited by three different classes of compounds: local anaesthetics, pentobarbitone and ethanol. The inhibitory action of the local anaesthetics increases with an increase in pH, the inhibitory action of pentobarbitone increases with a decrease in pH and the inhibitory action of ethanol is not affected by variations in Tyrode pH.

. It is suggested that the antagonists are active when unionized and that the inhibition is obtained when unionized compounds have dissolved in the lipid material of the cell membrane. The possible site of action of the antagonists is discussed.
Acceleration of noradrenaline biosynthesis in the guinea‐pig vas deferens by potassium
Authors: BOADLE‐BIBER MARGARET C. , HUGHES J. , ROTH R. H.
Published: July 2012

. Increasing the concentration of KC1 in Krebs‐Henseleit bicarbonate solution enhanced the formation of 14C‐noradrenaline (14C‐NA) from 14C‐tyrosine in the guinea‐pig vas deferens. In 52 mm KC1 Krebs‐Henseleit solution the specific activity of the newly formed 14C‐NA was double that of controls.

. The rate of synthesis of 14C‐NA from 14C‐tyrosine was constant for up to 2 h in 52 mm KC1 Krebs‐Henseleit solution and for 4 h in unmodified Krebs‐Henseleit solution.

. There was no increase in NA formation in the presence of KC1 rich Krebs‐Henseleit solution if 14C‐DOPA was used as the starting substrate instead of 14C‐tyrosine.

. The specific activity of 14C‐tyrosine in the high KC1 treated vas deferens was 80% of that of control tissues. Thus the enhanced synthesis of 14C‐NA in high KC1 Krebs‐Henseleit solution did not arise from an increase in the specific activity of precursor.

. The effect of K+ on NA synthesis was not mimicked by ganglionic stimulants nor blocked by tetrodotoxin.

. Removal of Ca2+ ions or increasing the concentration of Mg2+ ions abolished the increase in synthesis of NA seen in high KC1 Krebs‐Henseleit solution but left the basal rate of NA synthesis in unmodified Krebs‐Henseleit solution unaltered.

. The spontaneous release of newly synthesized catecholamines (14C‐labelled) or tritiated noradrenaline (3H‐NA) from vasa deferentia was increased in 52 mm KC1 Krebs‐Henseleit solution. Removal of Ca2+ ions reduced the increased efflux of newly synthesized amine in high KC1 media to that seen in unmodified Krebs‐Henseleit solution. The efflux of 3H‐NA was reduced to one‐third of its former rate in the absence of Ca2+.

. High KC1 Krebs‐Henseleit solution caused a substantial contraction of the vas deferens which was not abolished by tetrodotoxin. Release of 3H‐NA paralleled the contractile response, and was likewise unaffected by tetrodotoxin.

. No evidence was obtained for any alterations in the activity of tyrosine hydroxylase, the rate limiting enzyme in the formation of NA from tyrosine, in homogenates of vas deferens which had been treated with 52 mm KC1 Krebs‐Henseleit solution.

. These results support the hypothesis that acceleration of NA synthesis occurs when tyrosine hydroxylase is freed from end‐product inhibition by the release of noradrenaline, brought about in this case, by high concentrations of KC1.
Effects of intraventricular 2,4,5‐trihydroxyphenylethylamine (6‐hydroxydopamine) on rat behaviour and brain catecholamine metabolism
Authors: LAVERTY R. , TAYLOR K. M.
Published: July 2012

. 6‐Hydroxydopamine (200 μg injected intraventricularly) caused depletion of noradrenaline from all regions of rat brain within 2 h after injection but depletion of dopamine in the brain was observed only from 2 days after injection. Both catecholamines remained depleted for more than 32 days.

. Rats treated with intraventricular 6‐hydroxydopamine were sedated and lethargic, with reduced spontaneous and exploratory activity, for periods of up to 8 days after injection. Conditioned avoidance responding was abolished or reduced for a similar period.

. Intraventricular 6‐hydroxydopamine caused a prolonged reduction in the amount of labelled catecholamines in store 4 h following an intraventricular injection of 3H‐dopamine. During the first 6 h after 6‐hydroxydopamine injection, there was a marked increase in neutral and acid metabolites from the labelled catecholamines.

. A comparison of the behavioural and biochemical effects of intraventricular 6‐hydroxydopamine and reserpine suggests that both drugs affect catecholamine storage mechanisms but by different mechanisms. It was not possible from these experiments to correlate behavioural changes with either catecholamine storage or metabolism.
Stimulating action of atropine on the release of acetylcholine by rat cerebral cortex in vitro
Authors: POLAK R. L.
Published: July 2012

In cortical slices from rat brain incubated in a medium containing the irreversible cholinesterase inhibitor, soman (0·005 mm) and a high concentration of KCl (25 mm), atropine exerts a stimulating action on the release of acetylcholine (ACh).

Two possible explanations for this action were examined. Atropine might expel ACh from the nerve endings by occupying its storage sites or it might prevent an inhibitory action of the released ACh on its further release by occupying muscarinic receptors at the presynaptic endings; its action would then be a kind of ‘disinhibition.’

The stimulating action of atropine on ACh release persisted during prolonged incubation (up to 3·5 h) provided choline was added to the medium. This finding would be difficult to explain if atropine acted by expelling ACh from its storage sites.

The stimulating action of atropine on ACh release was inhibited by oxotremorine and by methacholine, added to the medium in high concentrations. This finding is readily explained if atropine acts by ‘disinhibition.’
Antinociceptive activity of morphine after injection of biogenic amines in the cerebral ventricles of the conscious rat
Authors: SPARKES C. G. , SPENCER P. S. J.
Published: July 2012

A simple cannula and a cannula guide for making injections into the cerebral ventricles of conscious rats are described.

Intraventricular injections of 5‐hydroxytryptamine (5‐HT) or of noradrenaline (NA) were without effect on the nociceptive threshold of rats.

Intraventricular injection of 5‐HT potentiated the antinociceptive effect of morphine. Reserpine pretreatment antagonized the antinociceptive effect of morphine; this effect was reversed by intraventricular injection of 5‐HT.

Intraventricular injection of NA attenuated the antinociceptive action of morphine but was without effect on the inhibition by reserpine of the antinociceptive effect of morphine.

Subcutaneous injection or slow intravenous infusion of either 5‐HT or NA (up to 300 μg/rat) were without significant effect on the antinociceptive effects of morphine.

Intraperitoneal administration of dopa increased the nociceptive threshold above normal, but reduced the antinociceptive effect of morphine. Intraventricular injection of either dopa or dopamine had no antinociceptive effect but inhibited that of morphine.

It is suggested that the antinociceptive effect of morphine may depend on the balance between the concentrations of 5‐HT and NA in the brain.
Effect of diuretics on mouse blood sugar following single dose administration
Authors: FOY J. M. , FURMAN B. L.
Published: July 2012

Frusemide, in doses which were maximal or supramaximal in respect of its natriuretic, diuretic and kaliuretic properties, produced a dose dependent, transient hyperglycaemic response in the mouse.

Bilateral nephrectomy resulted in a complete abolition of the hyperglycaemic response.

The hyperglycaemic response was accompanied by a decrease in liver glycogen and was significantly attenuated by adrenalectomy, adrenal demedullation and pretreatment with dihydroergotamine (DHE).

In the nephrectomized mouse frusemide treatment produced a marked reduction in intravenous glucose tolerance and a reduction in the plasma concentration of immunoreactive insulin following glucose administration. The drug had no detectable effect upon insulin sensitivity.

Hydrochlorothiazide exerted no detectable effect on mouse blood sugar.

Ethacrynic acid hyperglycaemia was obtainable after intraperitoneal or intramuscular injection, but not after intravenous injection. Intravenously administered ethacrynic acid exerted no effect upon intravenous glucose tolerance or insulin sensitivity in the nephrectomized mouse.
Adrenoceptor functions in the cat choledochoduodenal junctionin vitro
Authors: PERSSON C. G. A.
Published: July 2012

The effects of α‐ and β‐adrenoceptor stimulating agents were investigated on three different kinds of preparation of the isolated sphincter of Oddi and on the duodenum of the cat.

Adrenaline (1·5 × 10−7m–6·3 × 10−7m), noradrenaline (1·6 × 10−7m–6·3 × 10−7m), and tyramine (2·9 × 10−6m–5·8 × 10−6m) increased the activity and tonus of the sphincter musculature and decreased duodenal activity and tone. The effect on the sphincter resulted in increased resistance to flow through the sphincter. The excitatory effects on the sphincter were blocked by phenoxybenzamine (1·7 × 10−8m–1·7 × 10−7m).

No effect was produced by tyramine in concentrations up to 4·6 × 10−5mon sphincters taken from reserpinized cats. It is suggested that the cat sphincter of Oddi contains adrenergic nerves of functional importance.

Isoprenaline (1·9 × 10−8m–4·7 × 10−7m) and terbutaline (3·5 × 10−7m–8·8 × 10−6m) decreased spontaneous activity and tonus of the sphincter, and diminished resistance to flow through the sphincter. Both agents decreased spontaneous activity and tonus of the duodenum. On a molar basis, isoprenaline was 2–18 times more active than terbutaline on the sphincter and 35–90 times more active on the duodenum. The effects of isoprenaline and terbutaline were blocked by propranolol (3·9 × 10−7m).

It is concluded that the cat sphincter of Oddi contains α‐adrenoceptors active in contraction of the sphincter, and β‐adrenoceptors active in its relaxation. The β‐adrenoceptors of the sphincter differ from those in the duodenum; it is suggested that they belong to the β2‐group (according to Lands' classification).

The automaticity of the isolated sphincter of Oddi resembled the sphincter activity recordedin vivoand is probably myogenic in nature, as it resisted treatment with phenoxybenzamine (1·7 × 10−8m–1·7 × 10−7m), atropine (1·4 × 10−6m–5·8 × 10−6m), hexamethonium (1·4 × 10−5m–1·1 × 10−4m) and tetrodotoxin (1 μg/ml). The activity of the sphincter has no propulsive function but prevents passage of fluid through the sphincter.
Importance of the sympathetic nervous system in the development of renal hypertension in the rat
Authors: GREWAL R. S. , KAUL C. L.
Published: July 2012

Chemical sympathectomy with 6‐hydroxydopamine (6‐OHDA) prevented the development of renal hypertension in 80% of weanling male rats of the C.F. strain.

Adult male rats treated with 6‐OHDA developed hypertension on bilateral clamping of the renal arteries.

Demedullation of the adrenal glands followed by 6‐OHDA treatment in adult rats prevented the development of hypertension in 75% of them.

Weanling rats treated with 6‐OHDA did not have any measurable catecholamines in their hearts up to 72–78 days after treatment.

Unlike the weanling rats, the hearts of adult rats (demedullated or with intact medulla) showed significant refilling (40–50%) of catecholamine stores 60 days after 6‐OHDA treatment.

It is concluded that the functional sympathetic nervous system is important in the development of renal hypertension in the rat.
Effect of thermal injury on the kinin system in rabbit hind limb lymph
Authors: LEWIS G. P. , WAWRETSCHEK W. A.
Published: July 2012

The kinin‐forming activity of hind limb lymph and of plasma has been examined in rabbits before and after thermal injury.

Neither plasma nor lymph contained much active kallikrein activity but the enzyme was evident in samples treated with glass or with acid.

There was little or no increase in the activity of enzyme activated by glass after thermal injury, but an increase in the activity of enzyme activated by acid regularly occurred.

There were two increases in the activity of enzyme activated by acid—one about 2 h and the other 4–6 h after thermal injury. They corresponded to increases in vascular permeability as indicated by increases in the concentration of lymph protein.

There was considerably more kininogen in the lymph and plasma than was used in the assays of kallikrein activity, showing that the increased kinin‐forming activity in lymph was not the result of the passage of kininogen from the plasma.

The increase in activity in lymph was not usually accompanied by a similar increase in the plasma. However, an increase in the activity of enzyme activated by acid sometimes occurred in the plasma simply as a result of prolonged anaesthesia.

It is suggested that whereas the enzyme activated by glass is a measure of prekallikrein, the acid activatable enzyme appears as a result of the dissociation of a kallikrein‐inhibitor complex. An increase in the concentration of this complex is therefore an indication of the preceding activation of kallikrein.
Effects of isoprenaline and phenylephrine on energy‐rich phosphate compounds and glucose‐6‐phosphate in smooth and cardiac muscle
Authors: WESTON A. H.
Published: July 2012

Tension changes produced by phenylephrine and isoprenaline have been examined in four tissues—the guinea‐pig taenia coli, the longitudinal muscle strip of rabbit duodenum, the abdominal aorta of the rabbit and the rat heart.

Changes in the amounts of adenosine triphosphate (ATP), creatine phosphate (CP) and glucose‐6‐phosphate (G‐6‐P) associated with the addition of phenylephrine and isoprenaline have been measured in the four tissues using enzymatic fluorimetric analysis.

An α‐adrenoceptor‐mediated increase in tension (phenylephrine; rabbit aorta) was associated with no change in the amounts of ATP, CP or G‐6‐P.

An α‐adrenoceptor‐mediated decrease in tension (phenylephrine; guinea‐pig taenia coli and rabbit duodenum) was associated with no change in the amounts of ATP, CP or G‐6‐P.

A β‐adrenoceptor‐mediated increase in force of contraction (phenylephrine and isoprenaline; rat heart) was associated with a reduction in the amounts of ATP and CP and an increase in the amount of G‐6‐P.

A β‐adrenoceptor‐mediated decrease in tension (isoprenaline; guinea‐pig taenia coli and rabbit duodenum) was associated with an increase in the amounts of ATP and CP and no change in the amount of G‐6‐P.

β‐Adrenoceptor‐mediated metabolic changes were antagonized by propranolol.