bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure‐activity relations for the inhibition of catecholamine uptake into synaptosomes from noradrenaline and dopaminergic neurones in rat brain homogenates
Authors: HORN A. S. 
Published: July 2012

Summary
The effects of various phenylethylamine analogues on the inhibition of 3H‐noradrenaline and 3H‐dopamine uptake into homogenates of rat hypothalamus and corpus striatum respectively, were examined.
Phenolic hydroxyl groups and α‐methylation of the side chain were both found to enhance the affinity for the neuronal uptake sites.
Methoxylation, β‐hydroxylation and N‐methylation were all found to reduce the ability of a compound to inhibit catecholamine transport.
The noradrenaline and dopamine transport systems responded in a quantitatively different manner to the various phenylethylamine analogues. It was found that, in general, the noradrenaline uptake process was more sensitive to structural changes, both positive and negative, than the dopamine system.
An anti‐curare effect of hexamethonium at the mammalian neuromuscular junction
Authors: FERRY C. B. , MARSHALL A. R. 
Published: July 2012

Summary
Experiments were performed on the isolated phrenic nerve and diaphragm preparation of the rat.
In preparations partly blocked with (+)‐tubocurarine, the twitch amplitude increased after hexamethonium. This enhancement was not seen in preparations partly blocked with Mg++ or with gallamine. High concentrations of hexamethonium produced failure of contraction.
Extracellular endplate potentials were recorded from blocked preparations. The administration of hexamethonium resulted in an increased amplitude of these potentials only in curarized muscle.
Hexamethonium had no anticholinesterase activity nor did it depolarize muscle cells or increase the quantal release of transmitter.
It is concluded that hexamethonium exerts a specific anti‐curare action. Experiments on the recovery of the twitch after washing out antagonists indicate that this process is limited by diffusion. The difference in rates of diffusion of hexamethonium and (+)‐tubocurarine does not account for their interaction. The basis of the anti‐curare action of hexamethonium is discussed.
Effects of angiotensin, catecholamines and cyclic AMP on calcium storage in aortic microsomes
Authors: BAUDOUIN‐LEGROS M. , MEYER P. 
Published: July 2012

Summary
The binding of calcium observed in microsomal membranes derived from the intimal‐medial layer of rabbit aorta was specifically increased by the magnesium salt of adenosine triphosphate (Mg‐ATP). This calcium uptake was inhibited by potassium and sodium.
Angiotensin II, both in the presence and in the absence of Mg‐ATP, reduced the binding of calcium and increased the release of membrane‐incorporated calcium. These effects were dose‐dependent. Analogues of angiotensin II devoid of intrinsic activity, failed to alter the release of calcium.
Dibutyryl‐cyclic AMP increased the binding of calcium and reduced the rate of its release. The maximal effect was observed at the concentration of 10−5m.
(—)‐Noradrenaline reduced the binding of calcium; this effect was inhibited by phenoxybenzamine. Conversely, adrenaline like cyclic AMP, increased the calcium binding; the effect of adrenaline was suppressed by a β‐adrenoceptor blocking agent.
These observations demonstrate the existence of membranes in rabbit aorta capable of storing calcium. Excitatory drugs seem to affect directly and specifically the binding and release of calcium in these membranes.
Inhibition by γ‐hydroxybutyrate of chlorpromazine‐induced increase in homovanillic acid
Authors: ROTH R H. 
Published: July 2012

Summary
γ‐Hydroxybutyrate and its lactone precursor, γ‐butyrolactone, when administered in anaesthetic doses block the increase in the cerebral concentration of homovanillic acid normally observed after administration of chlorpromazine or haloperidol.
Other hypnotics such as glutethimide, urethane, chloralose, chloral hydrate and thiopentone do not have this ability even when administered in anaesthetic doses.
The ability of γ‐hydroxybutyrate to block the neuroleptic‐induced increase in cerebral homovanillic acid is not due to a reduction in body temperature since a similar effect is observed in rats treated under conditions (32° C) in which body temperature remains normal.
Possible mechanisms for this action of γ‐hydroxybutyrate are discussed.
On the pharmacology of the γ‐aminobutyric acid receptors on the cuneo‐thalamic relay cells of the cat
Authors: KELLY J. S. , RENAUD L. P. 
Published: July 2012

Summary
γ‐Aminobutyric acid (GABA) and glycine applied by iontophoresis were equipotent depressants of cuneo‐thalamic relay neurones isolated from the middle third of the cuneate nucleus of cats either decerebrated or anaesthetized with sodium pentobarbitone.
Glycine 13±2 nA and GABA 20±2 nA were equipotent depressors of hair cells (n = 22) and, bicuculline applied by iontophoresis caused a parallel shift to the right of the GABA but not the glycine log‐current response curves. The GABA equipotent dose‐ratio was 2·0 ± 0·2 for bicuculline currents of approximately 144 nA lasting about 11 min in cells excited either transynaptically by peripheral stimulation or postsynaptically by glutamate.
Although a maximal bicuculline current seldom caused a significant shift of the glycine‐log current response curve, many of our records show the onset of the glycine response to be slowed by doses in excess of 84 nA.
Bicuculline also antagonized depressions by β‐guanidinopropionic acid, and δ‐aminovaleric acid which mimicked the action of GABA.
When tested on the same neurone, bicuculline and picrotoxin applied by iontophoresis were equipotent and their effects appear to be additive.
The GABA sensitivity was not modified by repetitive (5 or 6) doses of i.v. bicuculline (0·2 mg/kg).
The antagonism of GABA by bicuculline and picrotoxin appears to be of sufficient specificity to enable the separate roles of GABA and glycine as putative inhibitory transmitters of cuneo‐thalamic relay cells to be determined.
Fate of angiotensin I in the toad Bufo melanostictus
Authors: NG K. K. F. 
Published: July 2012

Summary
The effects of angiotensin I and II on the blood pressure of pithed toads and the disappearance of angiotensin I and II in the perfused organs of the toad were studied.
Angiotensin I was relatively inactive on the blood pressure of pithed toads; it exhibited less than 3% of the pressor activity of angiotensin II.
Angiotensin I was not converted to angiotensin II during passage through the lungs. There was also no evidence of net conversion during passage through the kidney and hind quarters.
During passage through the lungs, 33–50% of angiotensin I was removed and 25–50% was removed during passage through the hind quarters. No loss of activity was detected when angiotensin II passed through the kidneys.
Angiotensin II passed through the lungs and kidneys without loss but 25–50% disappeared during passage through the hind quarters.
The relatively low pressor activity of angiotensin I together with its lack of conversion to angiotensin II in isolated perfused organs suggest that the converting enzyme is absent in the toad, Bufo melanostictus.
The action of lanthanum and manganese on anaphylactic histamine secretion
Authors: FOREMAN J. C. , MONGAR J. L. 
Published: July 2012

Summary
In the concentration range 1 nm to 1 μm, lanthanum inhibited the calcium‐dependent component of anaphylactic histamine release, but was without effect on the component which was independent of calcium.
The inhibition of anaphylactic histamine release by lanthanum can be reversed by increasing the calcium ion concentration. The pA2 for the lanthanum‐receptor interaction was found to be 7·6.
Lanthanum also inhibited the activation of anaphylactic histamine release by strontium ions.
The inhibition of anaphylactic histamine release by lanthanum was reversed by eluting the lanthanum from the cells.
In the concentration range 1 to 300 nm, lanthanum had no effect on the histamine release induced by compound 48/80 in a calcium‐free medium, but the effect of calcium on the histamine release by compound 48/80 was antagonized by lanthanum in this range of concentrations.
At concentrations of 10 μm and greater, lanthanum induced a release of histamine in the absence of antigen.
In the concentration range 0·5 to 40 mm, manganese inhibited the calcium‐dependent component of anaphylactic histamine release, but was without effect on the component which is independent of calcium. The inhibition of anaphylactic histamine release by manganese could be reversed by increasing the calcium ion concentration.
Some studies on the influence of chlordiazepoxide on the social interaction of golden hamsters (Mesocricetus auratus)
Authors: POOLE T. B. 
Published: July 2012

Summary
The effects of a ‘minor’ tranquillizer (chlordiazepoxide) on the social behaviour of male golden hamsters were investigated.
Thirty‐six hamsters were divided into pairs. Each pair was placed in an arena measuring 1 m2; under these conditions the hamsters fought, but once a winner and loser emerged the relationship between the two animals became stabilized. The influence of 50 mg/kg chlordiazepoxide on this stable relationship was investigated and compared with normal behaviour in the arena.
Under the influence of chlordiazepoxide, hamsters showed a significant reduction in ‘aggression’, ‘defensive fighting’ and an increase in ‘investigation’.
When the data for winners and losers were analysed independently, the drug was seen to influence losers more than winners.
It is postulated that the primary influence of chlordiazepoxide is to reduce fear and as a result ‘investigation’ is probably affected indirectly as a behaviour pattern suppressed in an individual showing fear of its opponent.
Influence of reserpine‐induced depletion of noradrenaline on the negative feed‐back mechanism for transmitter release during nerve stimulation
Authors: ENERO MARIA A. , LANGER S. Z. 
Published: July 2012

Summary
The effects of depletion of endogenous noradrenaline by reserpine‐pre‐treatment on [3H]‐noradrenaline overflow elicited by nerve stimulation were determined in the isolated nerve‐muscle preparation of the cat's nictitating membrane.
Reserpine pretreatment (0·3 mg/kg, s.c., 4 days prior to the experiment) reduced the noradrenaline levels in the smooth muscle of the nictitating membrane to about 10% of the control values while granular retention of [3H]‐noradrenaline had recovered to nearly 40% of the controls.
In the reserpine‐pretreated tissue the fraction release per shock induced by nerve stimulation was 2·2‐fold higher than the value obtained in the untreated tissues. This effect was correlated with the degree of depletion of the noradrenaline stores rather than with the decrease in the response of the effector organ.
Phenoxybenzamine, 2·9 μm reduced the responses to nerve stimulation to the same extent in control and in reserpine‐pretreated tissues. Yet, this concentration of phenoxybenzamine increased by 13‐fold the overflow of the labelled transmitter in the controls and only by 3‐fold in reserpine‐pretreated tissues.
The decrease in effectiveness of phenoxybenzamine in enhancing transmitter overflow after reserpine‐pretreatment appears to be due to the decrease in the total release of the transmitter.
The results obtained support the view that in reserpine‐pretreated tissues decreased transmitter output reduces the activation of the presynaptic α‐adrenoceptors which mediate the negative feed‐back mechanism that regulates transmitter release by nerve stimulation.
The local graft versus host reaction in the rat as a tool for drug mechanism studies
Authors: BECK FRANCES J. , LEVY L. , WHITEHOUSE M. W. 
Published: July 2012

Summary
A local graft versus host reaction in rats permits the evaluation of drug action on (i) donor (parental) animals and (ii) recipient animals (F1 hybrid) prior to establishing a lymphoid cell graft to detect drugs which might attenuate immunocompetence over a prolonged period (e.g. steroids).
Treatment of the recipient animals after a lymphoid graft readily detects anti‐proliferative agents and may disclose other agents which interfere with the recognition of non‐self by viable graft cells.
Treatment of the cell graft in vitro before innoculation into the recipient animal permits the detection of alkylating agents, wihch effectively deactivate graft cells at non‐toxic concentrations.
Examples are given of how this reaction may be used to evaluate functionally the effects of chemical modification of the cell surfaces of lymphocytes and to detect active metabolites generated from a precursor drug (e.g. cyclophosphamide).
Some novel immunosuppressant drugs are described.
Effects of chlorpromazine on exploration and habituation in the rat
Authors: FILE SANDRA E. 
Published: July 2012

Summary
The effects of chlorpromazine, 2 and 4 mg/kg, on exploration were investigated under two independent influences—food deprivation and time of day.
Rats had three 3‐minute trials in a hole‐board apparatus; hole‐investigation (head‐dips) and general motor activity were recorded.
On trial 1 chlorpromazine reduced exploration to half the control level, but on trial 3 it had no effect on motor activity or head‐dips.
General activity habituated from trial 1 to 3 in all groups, but some of the drug groups did not show significant habituation of head‐dips, due to the low level of responding on trial 1.
Possible modulating influence of frontal cortex on nigro‐striatal function
Authors: GLICK S. D. , GREENSTEIN S. 
Published: July 2012

Summary
After administration of (+)‐amphetamine, rats with unilateral ablations of the frontal cortex rotated either ipsilaterally or contralaterally as a function of time after surgery.
At early postoperative intervals (1–7 days), rotation was towards the side of the lesion.
At later times (15–30 days), rotation was towards the intact side.
Repeated testing with amphetamine appeared to slow the time‐course of changes in rotational behaviour.
These results suggest that a dopaminergic nigro‐striatal system is modulated by the frontal cortex and that unilateral removal of the latter produces a denervation supersensitivity of the former.
The effect of N6‐2′‐0 dibutyryl 3′, 5′ cyclic adenosine monophosphate, imidazole and aminophylline on ganglionic transmission in the superior cervical ganglion of the cat
Authors: VARAGIĆ V. M. , ŽUGIĆ M. 
Published: July 2012

Summary
Dibutyryl cyclic AMP, injected towards the superior cervical ganglion of the cat, produced no consistent responses.
Imidazole, injected towards the ganglion, regularly produced facilitation, both during intermittent and continuous preganglionic stimulation. This effect was dose‐dependent and lasted 2–10 minutes.
Aminophylline, injected towards the ganglion, regularly produced depression of ganglionic transmission, both during intermittent and continuous preganglionic stimulation. This effect was also dose‐dependent and lasted 1–4 minutes. Papaverine produced the same type of response as aminophylline.
Imidazole potentiated the ganglionic response to 1,1‐dimethyl‐4‐phenylpiperazinium iodide (DMPP), while aminophylline depressed it.
The results of the present experiments are consistent with the view that cyclic AMP may have a mediating role in the process of ganglionic transmission.
Prostaglandin E2 and the bovine sphincter pupillae
Authors: POSNER J. 
Published: July 2012

Summary
The bovine isolated sphincter pupillae incubated in Krebs solution releases a biologically active substance tentatively identified as prostaglandin E2.
The prostaglandin did not appear to be of neural origin or to result merely from tissue degeneration.
The spontaneous release of prostaglandin E2‐like material was related to the tone of the sphincter. Output increased as tone was acquired after setting up the tissue and fell when various procedures were used to reduce the tone.
Low concentrations of E and F‐type prostaglandins produced slow, well‐sustained contractions of the atonic sphincter, prostaglandin E2 being the most potent of those tested. The responses to prostaglandin E2 were antagonized selectively by a prostaglandin antagonist SC‐19220 (a dibenzoxazepine derivative) which in higher concentrations caused dose‐dependent relaxations of the preparation.
Prostaglandins did not appear to modulate transmission from nerve to muscle in the sphincter.
The hypothesis that prostaglandin E2 might be produced to act as a local hormone causing tonic contraction of the sphincter pupillae is discussed.
The effects of E and A prostaglandins on gastric mucosal blood flow and acid secretion in the rat
Authors: MAIN I. H. M. , WHITTLE B. J. R. 
Published: July 2012

Summary
The effects of prostaglandins E1, E2, A1 and A2 on gastric acid secretion and mucosal blood flow were studied by means of a [14C]‐aniline clearance technique in the anaesthetized rat.
During intravenous administration of these prostaglandins, in doses which almost completely inhibited pentagastrin‐ and histamine‐induced acid secretion, a fall in clearance was observed.
Clearance per unit acid secretion increased during prostaglandin administration, precluding a primary reduction in mucosal blood flow as the mechanism of the antisecretory action.
Prostaglandins increased clearance during basal secretion, indicating a direct vasodilator effect on the gastric mucosa.
The possibility that endogenous prostaglandins contribute to functional vasodilatation in the gastric mucosa and that exogenous prostaglandins may be of clinical value in the treatment of peptic ulcer is discussed.
Some effects of histamine in the depolarized rat uterus
Authors: BLYTH D. I. 
Published: July 2012

Summary
The relaxant effect of histamine in the isolated rat uterus remained after the preparation was depolarized in a potassium Ringer.
The effect was abolished by the calcium‐chelating agent, ethyleneglycol bis‐aminoethyl ether‐tetraacetic acid (EGTA).
Histamine caused relaxation during calcium‐induced contractures in a depolarized uterus treated with EGTA, but did not produce relaxation during barium‐induced contractures.
While responses of a normally polarized rat uterus to acetylcholine were inhibited by histamine, those of a depolarized uterus were enhanced by histamine. The inhibitory effects of isoprenaline and papaverine on acetylcholine responses were maintained in depolarized preparations.
Both the enhancing effect of histamine on responses to acetylcholine and the relaxation of calcium‐induced contractures were abolished by burimamide, indicating that H2‐receptors mediate the effects of histamine in the depolarized tissue.
A reduction in the rate of exchange of calcium across the depolarized cell membrane was demonstrated with high concentrations of histamine.
The results are consistent with the hypothesis that in the rat uterus, the stimulation of H2‐receptors by histamine is accompanied by a reduction in calcium exchange across the membrane which may result in a decrease in the concentration of free intracellular calcium available to stimulate contraction of the myofilaments. Histamine may act by increasing the binding of calcium within the cell.
A comparison of phenylalkyl‐ and phenoxyalkyltrimethylammonium and triethylammonium salts; their apparent molal volumes at infinite dilution and effects on the frog rectus and guinea‐pig ileum preparations
Authors: BARLOW R. B. , FRANKS FIONA M. 
Published: July 2012

Summary
The effects of phenoxyalkyltrimethylammonium and triethylammonium bromides on the frog rectus preparation and on the isolated guinea‐pig ileum in the presence of hexamethonium have been compared with those of analogous phenylalkyltrimethylammonium and triethylammonium bromides. Affinity constants have been measured when possible.
The apparent molal volumes at infinite dilution of some of the compounds have been measured from estimates of density made with an Anton Paar precision density meter.
An ether oxygen occupies at infinite dilution in water only about one‐third of the volume occupied by a methylene group.
The replacement of methylene by ether oxygen reduces nicotine‐like activity and affinity for nicotine‐sensitive receptors. The reduction in affinity may be partly due to the decrease in size.
The replacement of methylene by ether oxygen reduces activity and affinity at muscarine‐sensitive receptors but in some compounds there is a bigger reduction in affinity than would be expected simply from the reduction in size.
It is suggested that the affinity of these compounds largely depends on hydrophobic bonding and that effects on water structure in the environment of the receptor may also be involved in the actions of agonists.
Observations on ‘fade’: a complication of the contractile response of smooth muscle to a large dose of an agonist
Authors: FASTIER F. N. , PURVES R. D. , TAYLOR K. M. 
Published: July 2012

Summary
A study has been made of the time course of contraction of guinea‐pig isolated ileum when suddenly exposed to a high concentration of acetylcholine, carbachol or histamine. With a sufficiently large dose there was a ‘fading’ of the abrupt initial contraction. A sustained contraction followed, provided that the agonist was not washed out of the organ bath.
The fade produced by giving large equipotent doses of acetylcholine and histamine simultaneously was substantially greater than that obtained by giving either agonist alone. It was comparable to that produced by a double dose of acetylcholine or histamine. This result does not support any explanation of fade based on receptor occupancy.
The extent of fade and the level of the sustained contraction were strongly affected by the calcium concentration of the bath fluid: the higher the calcium concentration the less was the fade. It is suggested that fade occurs when there is such intense stimulation of receptors that excitation‐contraction coupling becomes temporarily less efficient due to depletion of calcium from a store.
ANALYSIS OF THE EFFECTS ON BODY TEMPERATURE OF INTRACEREBROVENTRICULAR INJECTION IN ANAESTHETIZED DOGS OF GAMMA‐AMINOBUTYRIC ACID
Authors: DHUMAL V.R. , GULATI O.D. , RAGHUNATH P.R. , SIVARAMAKRISHNA N. 
Published: July 2012

The cerebral ventricles of dogs under intravenous pentobarbitone sodium anaesthesia, were perfused with artificial cerebro‐spinal fluid (CSF) at a rate of 0.4–0.5 ml/min from the ventricular to the aqueductal cannulae. The effluent was collected from the aqueductal cannula in 20 min samples. The animals' temperatures were recorded from the rectum.
γ‐Aminobutyric acid (GABA) 0.1–5 mg when injected into the ventricles produced variable temperature effects. Doses of 0.1 and 0.5 mg always produced hyperthermia and 1 and 5 mg doses sometimes produced hyperthermia and sometimes hypothermia.
Intraventricular perfusion with 2‐bromolysergic acid diethylamide (BOL) and hyoscine did not block hyperthermia. Tests on the rat isolated stomach strip or the guinea‐pig isolated superfused ileum for the possible release, respectively, of 5‐hydroxytryptamine or acetylcholine by GABA were negative.
When tested for the presence of prostaglandin E(PGE)‐like substances on the isolated rat stomach strip, both the control effluent and the GABA effluent showed activity, the latter being much more potent. There was a temporal correlation between this effect and hyperthermia. Intraventricularly administered sodium salicylate converted the GABA‐induced hyperthermia to hypothermia and blocked the release of PGE‐like substances.
Hypothermia induced by GABA alone or in the presence of sodium salicylate was associated with the release of noradrenaline into the effluent.
Intraventricular administration of GABA in reserpinized dogs produced hyperthermia and not hypothermia. Similar results were obtained with phentolamine perfusion in normal dogs.
Perfusion with calcium‐free solution blocked both the noradrenaline‐releasing and hypothermic actions of GABA.
It is concluded that hyperthermia associated with intraventricular injections of GABA is due to the release of PGE‐like substance and hypothermia is due to the release of noradrenaline.