bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPECIES DIFFERENCES IN THE BINDING OF COMPOUNDS DESIGNED TO FIT A SITE OF KNOWN STRUCTURE IN ADULT HUMAN HAEMOGLOBIN
Authors: BEDDELL C.R. , GOODFORD P.J. , STAMMERS D.K. , WOOTTON R. 
Published: July 2012

Oxygen dissociation curves are reported for human haemoglobins A1, FII, FI, A1C and Raleigh ifil valine → acetylalanine) and for horse haemoglobin in the absence and presence of 2,3‐diphos‐phoglycerate (DPG), or 4,4′‐diformyl‐2‐bibenzyl oxyacetic acid, or the bisulphite addition compound of the latter.
These haemoglobins were selected because their amino acid sequences are different at the DPG receptor site of human adult deoxyhaemoglobin.
The size of the shifts of the dissociation curves are in the sequence expected from the postulated numbers of interactions made by each compound with each haemoglobin type, based on the assumption of a common receptor site for the three compounds.
Multiple linear regression analysis shows that the free energies of interaction of the compounds with the haemoglobins may be predicted, to a first approximation, by summing the number of ionic and covalent bonds predicted for each effector‐receptor combination, a reversible covalent bond contributing about twice as much energy (‐6.78 kJmol−1) as an ionic interaction (−3.14 kJmol−1).
EFFECTS OF CERTAIN MUSCARINIC ANTAGONISTS ON THE ACTIONS OF ANTICHOLINESTERASES ON CAT SKELETAL MUSCLE
Authors: BRIMBLECOMBE R. W. , FRENCH MARY C. , WEBB SANDRA N. 
Published: July 2012

The effects of some muscarinic antagonists, namely, N‐ethyl‐2‐pyrrolidylmethyl‐cyclopentylphenyl glycollate (PMCG), N‐methyl‐4‐piperidyl‐phenylcyclohexyl glycollate (PPCG, racemate and R and S enantiomers) and 4′‐N‐methyl‐piperidyl‐l‐phenyl‐cyclopentane carboxylate (G3063) on organ o‐phosphate (sarin, soman)‐ and carbamate (neostigmine)‐induced twitch augmentation have been studied in cat soleus muscle.
The results of a preliminary study comparing the potency of sarin and soman in inhibiting the acetylcholinesterase activity of muscle in relation to the effect on the maximal twitch response indicated that there is not a simple relationship between degree of enzyme inhibition by these drugs and alteration of muscle function.
The muscarinic antagonists studied were capable of preventing or reversing sarin‐, soman‐ or neostigmine‐induced twitch augmentation. Doses sufficient to give complete protection from the effects of the anticholinesterase agents had little or no effect on the twitch response of normal muscle.
The protective action of these muscarinic antagonists is dose‐dependent but independent of known antagonist actions at muscarinic receptors.
The effects of some local anaesthetics (lignocaine, prilocaine, cinchocaine, procaine) and other membrane stabilizers (quinine, ketamine, chlorpromazine, triflupromazine) were compared with those of the muscarinic antagonists in an attempt to elucidate the mode of action of these acetylcholine antagonists. The evidence is insufficient to exclude the involvement of a membrane stabilizing action.
SENSITIVITY OF MOUSE VAS DEFERENS TO NEUROTRANSMITTERS: CHANGES AFTER MORPHINE TREATMENT
Authors: CONTRERAS ENRIQUE , MARTI M. CRISTINA 
Published: July 2012

The pharmacological responses of the isolated vas deferens of the mouse were investigated after acute and chronic treatment with morphine.
The addition of morphine to the bath did not alter the responses of the vas deferens to exogenous noradrenaline, adrenaline or dopamine.
Low doses of morphine depressed the responses to acetylcholine. Very high concentrations of the opioid (8.5 × 10−4m) completely abolished, in about 50% of the preparations, the responses to exogenous acetylcholine, while in the other 50% a potentiation of the responses to low concentrations of acetylcholine was observed.
The vas deferens of mice chronically treated with morphine showed increased sensitivity to exogenous noradrenaline, but decreased sensitivity to acetylcholine.
A fresh amount of morphine added to the bath enhanced the responses of morphine‐tolerant preparations to noradrenaline but not to dopamine or acetylcholine. The specificity of this phenomenon was demonstrated by the use of pentobarbitone instead of the opioid.
These results are in agreement with the theory that tolerance could result from a form of disuse supersensitivity.
ACTION OF PROSTAGLANDIN DEHYDROGENASE INHIBITORS ON PROSTAGLANDIN UPTAKE IN RAT ISOLATED LUNG
Authors: BAKHLE Y.S. 
Published: July 2012

The effects of some inhibitors of 15‐hydroxy‐prostaglandin dehydrogenase (PGDH) have been studied on the inactivation of prostaglandin E2 (PGE2) and 16, 16‐dimethyl PGE2 in rat isolated lung.
Bioassay was used to show that the inactivation of PGE2 and its methyl analogue, was inhibited by frusemide (10−3m), N‐ethyl maleimide (10−5m) and 5, 5′‐dithio‐bis‐2‐nitro‐benzoic acid (10−2m), but not by caffeine (2.5 × 10−3m).
The efflux of radioactivity from lung following injection of [14C]‐PGE2 was faster in lungs treated with frusemide, N‐ethyl maleimide or bromcresol green, than in untreated lungs.
Caffeine (10−3, 10−2m) did not change the rate of 14C‐efflux from lungs following injection of [14C]‐PGE2.
From these results it is concluded that those PGDH inhibitors that prevented prostaglandin inactivation in isolated lungs did so by inhibiting uptake of prostaglandin rather than by inhibiting PGDH.
THE EFFECTS OF OPIOID DRUGS AND OF LITHIUM ON STEROIDOGENESIS IN RAT ADRENAL CELL SUSPENSIONS
Authors: GIBSON A. , GINSBURG M. , HALL M. , HART S.L. 
Published: July 2012

The effects of opioid drugs and of Na+ replacement on steroidogenesis in rat adrenal cell suspensions were investigated.
In medium containing normal Na+ (156 mm), opioid antagonists but not opioid agonists reduced the steroidogenic response to adrenocorticotrophic hormone1–24. (ACTH1–24) but not to dibutyryl adenosine 3′,5′ cyclic monophosphate (db cyclic AMP).
Replacement of 50% Na+ in the medium by choline had no effect on steroidogenesis, but further reductions in Na+ content reduced the steroidogenic activity of both ACTH1–24 and db cyclic AMP.
In 50% Na+ medium both opioid agonists and antagonists inhibited ACTH1–24 induced steroidogenesis.
Addition of therapeutic concentrations of lithium to otherwise normal medium inhibited the steroidogenic response to ACTH1–24 but not to db cyclic AMP.
The selective inhibition of ACTH1–24‐induced steroidogenesis by opioid drugs suggests some similarity between the opioid and ACTH receptors.
The relevance of the potent inhibitory effect of lithium to its therapeutic actions is discussed.
THE ACTION OF MICROELECTROPHORETICALLY APPLIED (3,4‐DIHYDROXY‐PHENYLAMINO)‐2‐IMIDAZOLINE (DPI) ON SINGLE CORTICAL NEURONES
Authors: BEVAN P. , BRADSHAW C.M. , PUN R.Y.K. , SLATER N.T. , SZABADI E. 
Published: July 2012

The technique of microelectrophoresis was used in order to compare the actions of the imidazoline derivative, (3,4‐dihydroxy‐phenylamino)‐2‐imidazoline (DPI), with those of dopamine and phenylephrine on single neurones in the cerebral cortex of the rat anaesthetized with halothane.
DPI and phenylephrine were almost exclusively excitatory, whereas dopamine could evoke both excitatory and depressant responses.
In the case of excitatory responses, DPI appeared to be more potent than dopamine, and was approximately equipotent with phenylephrine.
The dopamine antagonist, haloperidol, could discriminate between excitatory responses to DPI and dopamine: responses to dopamine were abolished, whereas responses to DPI, and to a control agonist, acetylcholine, were unaffected.
The α‐adrenoceptor antagonist, phenoxybenzamine, antagonized equally excitatory responses to DPI and phenylephrine. Responses to acetylcholine were not affected.
It is concluded that DPI does not stimulate dopamine receptors on cortical neurones; the excitatory responses of these cells to DPI may be mediated by α‐adrenoceptors.
DRUG‐INDUCED CHANGES IN THE FORMATION, STORAGE AND METABOLISM OF TYRAMINE IN THE MOUSE
Authors: JUORIO A.V. 
Published: July 2012

The endogenous concentrations of p‐ and m‐tyramine in the mouse striatum were determined by a mass spectrometric integrated ion current technique and concentrations were 21.3 and 6.1 ng/g, respectively.
The present results further confirm that the administration of antipsychotic drugs (chlorpromazine, haloperidol, spiroperidol, α‐flupenthixol and (+)‐butaclamol) reduces p‐tyramine concentrations in the mouse striatum. In contrast, striatal m‐tyramine showed a tendency to increase, although only in the cases of haloperidol and (+)‐butaclamol were the differences statistically significant.
Administration of antipsychotic drugs to mice pretreated with tranylcypromine or clorgyline produced a significant reduction in striatal p‐tyramine when compared with the concentrations obtained in mice given a monoamine oxidase inhibitor. These results suggest that antipsychotic drugs reduce striatal p‐tyramine formation. The moderate increases produced by monoamine oxidase inhibitors on striatal m‐tyramine were not significantly changed after the administration of an antipsychotic.
Drugs that reduce dopamine turnover (apomorphine, piribedil, lergotrile, α‐methyl‐p‐tyrosine) significantly increased the concentration of striatal p‐tyramine. No significant changes were observed in striatal m‐tyramine concentrations after apomorphine, piribedil or lergotrile; α‐methyl‐p‐tyrosine produced a reduction in its concentration.
Drugs that impair amine storage (reserpine, tetrabenazine, oxypertine) reduced striatal concentrations of p‐tyramine. The m‐tyramine concentrations were also reduced by reserpine or tetrabenazine.
It is possible that striatal tyramines act as modulators, or transmitters, and control the activity of dopaminergic neurones.
CONTRACTURES ELICITED BY TETRAETHYLAMMONIUM IN AVIAN MUSCLE TREATED WITH METHOHEXITONE
Authors: ELLIOTT R.C. 
Published: July 2012

The chick biventer cervicis muscle immersed in methohexitone (8.8 × 10−5 m) responded to tetraethylammonium with contractures which were dose‐related. The ED50 for tetraethylammonium was 2.1 × 10−3 m.
In the absence of methohexitone, tetraethylammonium produced contractures only at much higher concentrations; these contractures were accompanied by fasciculations and neuromuscular block of the twitch fibres.
The contractures produced by tetraethylammonium in the presence of methohexitone were not reduced by exposure to botulinum toxin which eliminated all response of the muscle to indirect stimulation.
Tubocurarine (1.2 × 10−6 m) displaced the dose‐response curve for tetraethylammonium‐methohexitone‐induced contractures to the right. The dose‐ratio was 15.63 ± 1.98.
Physostigmine (1.8 × 10−6 m) potentiated the activity of tetraethylammonium‐methohexitone 3.26 or 3.84 fold, depending on the method of calculation used.
Physostigmine potentiated contractures elicited by indirect repetitive stimulation 4.8 to 6.0 fold more than it potentiated contractures due to tetraethylammonium‐methohexitone.
It is concluded that in the presence of methohexitone, tetraethylammonium produces contractures of the chick muscle by releasing acetylcholine but also by a direct agonist action on the cholinoceptor.
INVESTIGATION OF THE MECHANISM OF PROPRANOLOL‐INDUCED BRONCHOCONSTRICTION
Authors: MACLAGAN JENNIFER , NEY URSULA M. 
Published: July 2012

Dose‐related increases in airways resistance (Raw) and decreases in dynamic lung compliance (Cdyn) were recorded in guinea‐pigs and rats following intravenous injection of propranolol and of the cardioselective β‐adrenoceptor blocking drugs, atenolol and practolol.
The bronchoconstriction reached a peak in 2 to 4 min and subsided within 15 min. Repeated injections caused identical responses in the airways.
The isomer (+)‐propranolol, which has only weak β‐adrenoceptor blocking activity, produced identical responses when given alone or when given after a dose of the racemate, sufficient to cause measurable β‐adrenoceptor blockade in the lungs.
After the initial bronchospasm had subsided, the β‐adrenoceptor blocking drugs and the isomer, (+)‐propranolol, produced potentiation of the bronchoconstrictor effects of 5‐hydroxytryptamine and histamine.
Both the bronchospasm and the potentiation occurred in adrenal demedullated rats.
The results indicate that the bronchoconstrictor effects of these drugs are unrelated to β‐adrenoceptor blockade in the airway smooth muscle.
STIMULATION AND INHIBITION OF THE SODIUM PUMP BY CARDIOACTIVE STEROIDS IN RELATION TO THEIR BINDING SITES AND THEIR INOTROPIC EFFECT ON GUINEA‐PIG ISOLATED ATRIA
Authors: GHYSEL‐BURTON JOSIANE , GODFRAIND T. 
Published: July 2012

The actions of ouabain, ouabagenin and dihydroouabain on the contractility and on the ionic content have been investigated in left guinea‐pig atria stimulated at 3.3 Hz. The specific binding of ouabain and its displacement by the other cardenolides have been determined.
The action of either ouabain or ouabagenin on Na and K content was qualitatively different according to the concentration employed. Low doses evoked a reduction of Nai whereas high doses produced an increase. Dihydroouabain evoked only a Nai gain.
The increase of KCl concentration from 2.7 to 12 mm decreased Nai in untreated atria and displaced ouabain dose‐effect curves to the right.
ED50 values for the positive inotropic effect were lower than ED50 values for the inhibition of the pump and were not similarly affected by an increase in KCl concentration.
The specific binding of ouabain occurred at high and low affinity sites, related to Na pump stimulation and inhibition respectively.
The increase in KCl reduced the affinity of the two groups of sites for ouabain and increased the capacity of the high‐affinity sites whereas the capacity of the other sites remained unchanged.
The results confirm the existence of two specific binding sites for ouabain in guinea‐pig heart and suggest that the inhibition of the Na pump is not the only mechanism responsible for the positive inotropic effect of cardiac glycosides.
EFFECT OF 5‐HYDROXYTRYPTAMINE ON PROTEIN SYNTHESIS IN GASTROINTESTINAL AND OTHER TISSUES AND ON SERUM GASTRIN CONCENTRATIONS IN RATS
Authors: MAJUMDAR ADHIP P. NANDI , NAKHLA ATIF M. 
Published: July 2012

The effect of 5‐hydroxytryptamine (5‐HT) on protein synthesis in the gastrointestinal tissues as well as in the liver, heart and brain was studied by measuring [3H]‐leucine incorporation into total tissue protein in vivo in rats.
A single injection of 5‐HT (10 mg/kg) produced a marked inhibition (45 to 65%) in protein synthesis in the stomach (oxyntic gland area), intestine (jejunum + ileum), colon and brain, but not in the liver and heart.
Dose‐ and time‐dependent studies of 5‐HT‐induced changes in protein synthesis in the stomach of fed rats revealed that the maximal inhibition of about 65% occurred 1 h after a dose of 12.5 mg/kg.
Animals deprived of food for 24 h differed from their fed counterparts only in the degree of responsiveness, in that a greater inhibition (75%) of [3H]‐leucine incorporation into total protein of the stomach was observed 30 min after 5‐HT injection.
Pretreatment of animals with methysergide (0.25 mg/kg) essentially abolished the 5‐HT‐mediated inhibition of protein synthesis in the stomach.
Serum gastrin concentration in fasted animals remained slightly elevated during the initial period of 5‐HT treatment (up to 1 h).
The results demonstrate that in certain tissues, 5‐HT markedly inhibits protein synthesis. The inhibition in protein synthesis in the gastrointestinal tract cannot be attributed to changes in the concentration of gastrin.
RELATIONSHIP BETWEEN ACCUMULATION, STORAGE AND OVERFLOW OF NORADRENALINE IN THE RAT SALIVARY GLAND AFTER CHRONIC TREATMENT WITH GUANETHIDINE
Authors: KHAN MOHAMMAD T. , WAKADE ARUN R. 
Published: July 2012

The effect of guanethidine on the endogenous noradrenaline (NA) content, accumulation and overflow of [3H]‐noradrenaline ([3H]‐NA) in the rat salivary gland was examined at various times after drug administration.
Twenty‐four h after a single injection of guanethidine (1 or 10 mg/kg s.c), the respective values for the endogenous NA content and for the accumulation and overflow of [3H]‐NA were approximately 55, 85, 30%, and 15, 55, 10% of the controls.
Although [3H]‐NA accumulation had returned to control levels within 48 h after the dose of 10 mg/kg guanethidine, the overflow of [3H]‐NA evoked by electrical stimulation or excess potassium (K+) remained depressed.
After the low or the high dose of guanethidine, the NA content of the salivary gland was restored to about 50% of the normal value between 4 to 24 and 48 to 72 h, respectively.
The accumulation of [3H]‐NA was inhibited by about 75% by cocaine. The same degree of inhibition was obtained 4 h after 10 mg/kg guanethidine. In these experiments phenoxybenzamine did not reduce the residual (25%) uptake.
The reasons for differential rates of recovery of the endogenous NA content and the storage of [3H]‐NA after guanethidine are discussed.
EFFECTS OF β2‐ADRENOCEPTOR STIMULATION ON CARDIAC METABOLISM IN THE CONSCIOUS DOG
Authors: SHANAHAN E. ANNE , WAHLQVIST MARK L. , WILMSHURST ERROL G. 
Published: July 2012

The effects of the β2‐adrenoceptor stimulant, salbutamol, on cardiac metabolism have been studied in conscious mongrel dogs. The potential effects of anaesthesia on the study of cardiac metabolism have been avoided by prior implantation of arterial (A) and coronary sinus (CS) catheters for blood sampling and a central venous catheter for infusion. Extraction of substrates for myocardial energy metabolism (CA—CS) was assessed 3 to 24 days post‐operatively. A 100 μg bolus of salbutamol was given followed by an infusion of 3 μg/min for 1 h.
Although heart rate increased significantly from 106 to 165 beats/min, fractional extraction of oxygen tended to fall from 84% to 77%. Thus an increase in coronary blood flow rather than in oxygen extraction must have maintained an oxygen supply commensurate with the salbutamol‐induced tachycardia.
Neither CA—CS glucose nor fractional glucose extraction altered significantly during salbutamol infusion despite increases in arterial concentration (CA) of glucose and arterial insulin immunoreactivity and a decrease in CA of free fatty acids (FFA). This suggests that an insulin‐antagonistic action accompanies the infusion of salbutamol.
The fractional extraction of lactate increased during salbutamol infusion. In part, this may have been a reflection of a decreased myocardial extraction of FFA with salbutamol in this model.
CARDIOVASCULAR RESPONSES PRODUCED BY THE INJECTION OF DOPAMINE INTO THE CEREBRAL VENTRICLES OF THE UNANAESTHETIZED DOG
Authors: LANG W.J. , WOODMAN O.L. 
Published: July 2012

The injection of dopamine (100 to 500 μg) into the cerebral ventricles (i.c.v.) of 10 unanaesthetized dogs produced a dose‐dependent increase in arterial blood pressure and heart rate. The dogs licked, swallowed, sometimes vomited and became sedated.
Autonomic ganglion blockade with hexamethonium (10 mg/kg, i.v.) abolished cardiovascular responses to i.c.v. dopamine, indicating that dopamine was exerting its effect within the central nervous system.
The dopamine receptor antagonists, haloperidol (500 μg), chlorpromazine (200 μg) and ergometrine (500 μg), each given i.c.v., subsequently abolished the cardiovascular responses to dopamine.
Pretreatment with either the β‐adrenoceptor antagonist, propranolol (600 μg) or the α‐adrenoceptor antagonist, phentolamine (1 mg) given i.c.v. had no significant effect on the response to dopamine.
It is suggested that dopamine injected into the cerebral ventricles of the unanaesthetized dog causes hypertension and tachycardia by activating central dopamine receptors.
THE EFFECTS OF DISOPYRAMIDE PHOSPHATE ON EARLY POST‐CORONARY ARTERY LIGATION DYSRHYTHMIAS AND ON EPICARDIAL ST‐SEGMENT ELEVATION IN ANAESTHETIZED DOGS
Authors: MARSHALL R.J. , PARRATT J.R. 
Published: July 2012

The antidysrhythmic, haemodynamic and metabolic effects of intravenously administered disopyramide phosphate (1 to 5 mg/kg) have been studied in greyhounds, anaesthetized with trichloroethylene.
In doses of 2.5 and 5.0 mg/kg, disopyramide significantly reduced the ventricular dysrhythmias that occur in the initial 30‐min period following acute coronary artery ligation. None of the disopyramide‐treated animals developed ventricular fibrillation.
The metabolic consequences of coronary artery ligation, assessed by local coronary venous sampling from the ischaemic area, were not modified by disopyramide except that K+ egress was prevented.
There was evidence for substantial disopyramide‐induced myocardial depression (decreased cardiac output and left ventricular dP/dtmax with elevated ventricular filling pressure and pulmonary oedema and shunting) and it is suggested that great care be taken when the drug is administered intravenously in conditions where cardiac function is already compromised. Disopyramide also reduced myocardial blood flow.
In chloralose‐anaesthetized mongrel dogs, disopyramide (2.5 mg/kg) significantly reduced the ST‐segment elevation (assessed from epicardial recordings) that resulted from short (3 min) coronary artery occlusions. This could indicate a reduction in the extent and severity of myocardial injury or simply reflect decreased K+ efflux (since locally administered K+ itself increased ST‐segment elevation).
THE EFFECT OF SOME GENERAL ANAESTHETICS ON THE SURFACE POTENTIAL OF LIPID MONOLAYERS
Authors: BANGHAM A.D. , MASON W. 
Published: July 2012

This study sought to investigate the report by Ginsberg (1978) that 0.7 m ethanol brought about a +100 mV change (ΔΔV) in the surface potential of glyceryl monooleate (GMO) monolayers formed on KCl, although he predicted that a ΔΔV of −10 mV should have been found.
The effect of general anaesthetics such as n‐alkyl alcohols and pentobarbitone on surface potential (ΔV) and surface tension (γ) of lipid monolayers formed on 145 mm KCl from either glyceryl monooleate (GMO) or phosphatidyl choline (PC) was examined with an Americium‐241 air electrode assembly (ΔV) and a platinized platinum dipping plate and force balance (γ).
It was found that, as predicted by Ginsberg (1978), addition of 0.7 m ethanol to the aqueous phase bathing either PC or GMO monolayers brings about a negative‐going change in interfacial potential (ΔΔV).
The magnitude of ΔΔV is dependent in a linear fashion on ethanol concentration.
Longer chain length alcohols up to n‐decanol also bring about a negative going change in ΔΔV, and the dependence of ΔΔV on anaesthetic activity, with respect to increasing chain length of anaesthetic, is consistent with Traube's law.
Pentobarbitone added to the aqueous phase bathing the monolayer also elicits a negative ΔΔV, a finding which rules out the possibility of adsorption of the volatile alcohols to the measuring electrode.
The findings are discussed in terms of the proposition that increasing disorder in an array of fixed dipoles, such as might occur in a bilayer exposed to anaesthetic, would result in a lowering of the electrostatic barrier to the predominantly impermeable cation.
EFFECTS OF NORADRENALINE AND CARBACHOL ON TEMPERATURE REGULATION OF COLD‐STRESSED AND COLD‐ACCLIMATED RATS
Authors: POOLE S. , STEPHENSON J.D. 
Published: July 2012

Noradrenaline (20 μg) and carbachol (1 μg) injected into the anterior hypothalamus of rats at an ambient temperature of 23°C evoked significant falls in core temperature and increases in tail temperature.
When rats were cold‐stressed (4°C for 90 min) or cold‐acclimated (4°C for 4 weeks) and the above amine injections repeated, only carbachol evoked significant falls in core temperature and neither amine increased tail temperature.
Central injections of noradrenaline and carbachol also evoked increases in plasma glucose concentrations but not plasma non‐esterified fatty acid (NEFA) concentrations in control, acutely cold‐stressed and cold‐acclimated rats.
Although concentrations of plasma glucose and blood lactate of rats were unaffected by cold exposure to 4°C for 1 to 28 days, glucose oxidation rate of both cold‐stressed and cold‐acclimated rats was significantly greater than in rats at 23°C. Concentrations of plasma NEFA were increased after 1 to 28 days of cold exposure.