bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Summary
. 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

Summary
. 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

Summary
. 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

Summary
. 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

Summary
. 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

Summary
. 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

Summary
. 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.