bluuebunny/crossref_metadata_2025_split huggingface dataset:
STUDIES ON THE MECHANISM OF ACTION OF AMANTADINE
Authors: BROWN F. , REDFERN P.H. 
Published: July 2012

The effect of amantadine hydrochloride on various aspects of catecholamine metabolism in the rat brain has been investigated.
Amantadine failed to have any significant effect on brain concentrations of dopamine or noradrenaline even when administered daily for 9 days.
Amantadine had no effect on the rate of decline of noradrenaline and dopamine concentrations after α‐methyl‐p‐tyrosine.
In vitro, amantadine inhibited dopamine uptake into synaptosomes only at high concentrations, and caused little release of dopamine from synaptosomes.
There is no evidence from these results to suggest that the anti‐Parkinsonian effect of amantadine is related to an action on dopaminergic mechanisms.
THE EFFECTS OF pH ON THE ACTIVITY OF CORYNEINE AND RELATED PHENOLIC QUATERNARY AMMONIUM SALTS ON THE FROG RECTUS PREPARATION
Authors: BARLOW R.B. 
Published: July 2012

The activity of m‐hydroxybenzyltrimethylammonium, coryneine (3:4‐dihydroxyphenethyl‐trimethylammonium, ‘quaternary dopamine’), and m‐hydroxyphenylpropyltrimethylammonium relative to tetramethylammonium has been measured on the frog rectus preparation (Rana pipiens) at pH 7 and pH 9.
The compounds are more active in the more acid environment indicating that ionization of the phenolic group reduces activity to between one‐half and one‐tenth of that of the form with the intact hydroxyl group.
In contrast with the situation at aminoacid receptors, there is no reason to believe that at other receptors zwitterions are likely to be more active than the uncharged forms with which they are in equilibrium.
INTERACTIONS OF ISOPRENALINE AND PROSTAGLANDIN E2 WITH RESPECT TO MYOCARDIAL CONTRACTILE FORCE, CORONARY VASCULAR RESISTANCE AND MYOCARDIAL OXYGEN CONSUMPTION IN GUINEA‐PIG ISOLATED HEARTS
Authors: KREBS R. , SCHRÖR K. 
Published: July 2012

Left ventricular pressure (LVP), left ventricular pressure derivative (LV dp/dtmax), coronary vascular resistance (CVR) and myocardial oxygen consumption (Qo2) were measured simultaneously in isolated, electrically driven hearts of guinea‐pigs at constant perfusion rate.
LVP, LV dp/dtmax, CVR and Qo2 were greatly decreased by either the addition of prostaglandin E2 (50 ng/ml) to the perfusion fluid or pretreatment of the animals with reserpine.
Isoprenaline (0.5 nm to 100 nm) induced increases in LVP, LV dp/dtmax. and Qo2. In the presence of prostaglandin E2, there was a parallel shift of the isoprenaline concentration‐response curve for LVP and LV dp/dtmax. This effect was not seen, after the animals had been treated with reserpine.
Qo2 was also decreased by prostaglandin E2 only in non‐reserpine treated animals.
CVR was diminished by isoprenaline in the untreated group. However, there was increase in CVR, when isoprenaline was added to either prostaglandin E2 or reserpine‐pretreated hearts which was enhanced in the reserpine plus prostaglandin E2‐treated group (P < 0.01).
The results give evidence for different actions of prostaglandin E2 on isoprenaline concentration‐response curves for LVP, LV dp/dtmax and CVR.
EFFECT OF IONOPHORE X‐537A ON DESENSITIZATION RATE AND TENSION DEVELOPMENT IN POTASSIUM‐DEPOLARIZED MUSCLE FIBRES
Authors: DeBASSIO W.A. , PARSONS R.L. , SCHNITZLER R.M. 
Published: July 2012

The effects of the ionophore X‐537A were studied on carbamylcholine (carbachol)‐induced desensitization and on tension development in relaxed potassium‐depolarized frog sartorius muscles.
X‐537A accelerated carbachol‐induced desensitization in Ca2+‐deficient solutions without having any effect on the conductance of the membrane in the absence of carbachol or on the extent of the carbachol‐induced increase in conductance.
In Ca2+‐deficient solution, the acceleration of desensitization by the ionophore was concentration‐dependent. No effect was observed with concentrations less than 5 μm and maximal acceleration was evident with 10 μm.
The influence of X‐537A on desensitization was time‐dependent. At 20 μm X‐537A, there was a marked acceleration of desensitization by the end of 5 min exposure. An additional gradual acceleration occurred during a 5 to 30 min treatment. No acceleration of desensitization was evident when X‐537A was simultaneously applied with carbachol to the end‐plate region without prior exposure to the ionophore.
Desensitization also was accelerated by 30 min exposure to 20 μm X‐537A in solutions containing Ca2+ or deficient in both Mg2+ and Ca2+; the rate being increased 2.8‐fold in Ca2+‐containing solutions, 2.9‐fold in Ca2+‐deficient solutions containing Mg2+, and 2.5‐fold in divalent cation‐deficient solutions.
Tension development gradually occurred in relaxed potassium‐depolarized muscle preparations exposed to 20 μm X‐537A. The onset of tension development occurred only after approximately 25 min of exposure both in preparations kept in Ca2+‐deficient or Ca2+‐containing solutions. By the end of 90 min in the ionophore, the tension developed was approximately 12% and 23% of the initial potassium contracture in those preparations maintained in the Ca2+‐deficient or Ca2+‐containing solutions, respectively.
We assume that the increase in desensitization rate following exposure to X‐537A results from an elevation of the intracellular Ca2+ concentration. That muscle tension gradually increased during exposure to the ionophore supports this conclusion. The acceleration of desensitization by X‐537A in the absence of external Ca2+ supports the view that the site of calcium acceleration is not on the external surface of the end‐plate membrane either at or near the agonist‐recognition site but rather on the inner surface.
ON THE DECREASE OF MYOCARDIAL OXYGEN CONSUMPTION INDUCED BY CHLORACYZINE
Authors: KISIN I.E. 
Published: July 2012

The effects of chloracyzine (2‐chloro‐10‐(3‐diethylaminopropionyl)‐phenothiazine hydrochloride; antianginal drug) on myocardial oxygen consumption were studied in open‐chest cats and cat isolated hearts using oximetry and polarography respectively.
It was found that chloracyzine produced a decrease in myocardial oxygen consumption accompanied by a reduction in coronary blood flow preceded by transient coronary dilatation. Chloracyzine produced an insignificant increase in arterial pressure; heart rate increased slightly in the open‐chest experiments but not in the isolated heart.
It is suggested that reduced oxygen uptake after chloracyzine is realized through improved efficiency in the use of oxygen.
EFFECT OF INDOMETHACIN AND PROSTAGLANDIN ON THE SMOOTH MUSCLE CONTRACTING ACTIVITY OF ANGIOTENSIN AND OTHER AGONISTS
Authors: ABOULAFIA JEANNINE , MENDES GUN B. , MIYAMOTO MARIA E. , PAIVA A.C.M. , PAIVA THEREZINHA B. 
Published: July 2012

Indomethacin had an equal inhibitory effect on the response of the guinea‐pig isolated ileum to angiotensin II (angiotensin), bradykinin, histamine and acetylcholine. This effect did not seem to result from inhibition of prostaglandin synthesis, as it did not depend on the time of treatment with indomethacin.
Prostaglandin E2 (prostaglandin) potentiated the responses of the guinea‐pig ileum to angiotensin, bradykinin, histamine and acetylcholine without significant differences in the effects observed.
In the rabbit isolated mesenteric and coeliac arteries, indomethacin had an equal potentiating effect on the responses to angiotensin and to adrenaline. In these organs pre‐incubation with indomethacin was necessary for the effect to be observed, and this effect lasted for 2 h or more after that drug was removed from the medium.
No cross‐tachyphylaxis between angiotensin and adrenaline was observed in the rabbit mesenteric and coeliac arteries.
It is concluded that the effects of indomethacin and prostaglandin on the response of the guinea‐pig ileum to the four agonists result from an action on the smooth muscle contractile mechanism per se rather than from an inhibitory action on the release of endogenous prostaglandin produced by the four agonists.
The results with the rabbit isolated arteries indicate that tachyphylaxis to angiotensin in these organs is not caused by prostaglandin release.
THE ACTION OF MICRO‐ELECTROPHORETICALLY APPLIED 1‐3,4‐DIHYDROXYPHENYLALANINE (DOPA) ON SINGLE CORTICAL NEURONES
Authors: BEVAN P. , BRADSHAW C.M. , SZABADI E. 
Published: July 2012

The technique of microelectrophoresis was used in order to compare the actions of l‐3,4‐dihydroxyphenylalanine (DOPA) and noradrenaline on single neurones in the cerebral cortices of cats and rats.
DOPA could both excite and depress cortical neurones. Cells excited by DOPA were also excited by noradrenaline and cells depressed by DOPA were also depressed by noradrenaline.
In the case of both excitatory and depressant responses, DOPA appeared to be less potent than noradrenaline.
Responses to DOPA and noradrenaline could be antagonized by phentolamine and propranolol. Responses to acetylcholine were not affected.
Responses to acetylcholine, but not responses to DOPA, were antagonized by atropine.
The results indicate that locally applied DOPA may mimic the actions of noradrenaline on cortical neurones. Possible mechanisms for these effects of DOPA are discussed.
THE LACK OF EFFECT OF OXYTETRACYCLINE ON RESPONSES TO SYMPATHETIC NERVE STIMULATION AND CATECHOLAMINES IN VASCULAR TISSUE
Authors: KALSNER S. 
Published: July 2012

The effects of oxytetracycline, an inhibitor of amine binding in connective tissue, on the responses of perfused rabbit ear arteries to sympathetic nerve stimulation and to intraluminally administered noradrenaline were examined. The contractions of aortic strips to catecholamines in the presence of oxytetracycline were also examined.
Oxytetracycline (0.1 mm) had no discernable effect on the magnitude of constrictions, measured as reductions in flow, produced by either nerve stimulation (0.5–10 Hz) or noradrenaline (0.5–50 ng) in the ear artery. In addition, the time taken for vessels to recover towards control flow values after endogenously released or exogenously applied noradrenaline had acted was not increased by oxytetracycline.
Oxytetracycline (0.1 mm) did not alter the position or shape of the concentration‐response curve to noradrenaline nor did it enhance the amplitude of individual responses to catecholamines in aortic strips.
It is concluded, contrary to the observations of Powis (1973), that oxytetracycline does not increase the magnitude or duration of responses to sympathetic nerve activation or to catecholamines and that binding to connective tissue is of no material consequence in terminating their action in vascular tissue.
DOPAMINE AND THE DEPRESSANT ACTION OF MORPHINE ON STIMULATED GUINEA‐PIG ILEUM
Authors: FERRI S. , REINA R. , SANTAGOSTINO A. 
Published: July 2012

Morphine reduces the amplitude of the contractions induced by electrical stimulation, in the myenteric plexus‐longitudinal muscle preparation of guinea‐pig ileum. Dopamine and apomorphine have the same effect but at much higher concentrations.
Dopamine, at concentrations lower than those which would normally be inhibitory, partially reverses the depressant effect of morphine.
Pre‐treatment of guinea‐pigs with 6‐hydroxydopamine results in a slight supersensitivity of innervated longitudinal muscle preparations to dopamine and has no effect on morphine activity.
Naloxone antagonizes the depressant effect of morphine but not that of dopamine or apomorphine.
The response of the ileum preparation to morphine is not affected by phentolamine or propranolol; the effect of dopamine, however, is abolished by α‐adrenoceptor blockade.
STRUCTURE‐ACTIVITY RELATIONSHIP OF VARIOUS CORTICOSTEROIDS ON THE FEEDBACK CONTROL OF CORTICOTROPHIN SECRETION
Authors: JONES M.T. , TIPTAFT ELIZABETH M. 
Published: July 2012

Several steroids occurring in the pathway of corticosteroid biosynthesis were investigated for their ability to exert a fast or delayed feedback inhibition of stress‐induced release of corticotrophin. Rats were injected subcutaneously with vehicle or a steroid either 10 min (fast feedback) or 4 h (delayed feedback) before they were subjected to stress which consisted of a 2 min exposure to ether vapour.
Changes in plasma corticosterone concentration and in vitro corticosterone production by excised adrenal glands were used as indices of corticotrophin release.
Among the steroids tested only 11β, 21‐dihydroxypregn‐4‐ene‐3, 20‐dione (corticosterone) and 11β, 14α, 21‐trihydroxypregn‐4‐ene‐3, 20‐dione (cortisol) inhibited the stress response 10 min after their administration. Therefore, it appears that the fast feedback mechanism is limited to steroids with a 21‐hydroxyl and a 11β‐hydroxyl group.
In contrast, many steroids caused inhibition of the stress response 4 h after their administration. These steroids were corticosterone, cortisol, 21‐hydroxypregn‐4‐ene‐3, 20‐dione (11‐deoxycorticosterone), 17α, 21‐dihydroxypregn‐4‐ene‐3, 20‐dione (11‐deoxycortisol), 11β‐hydroxypregn‐4‐ene‐3, 20‐dione (11β‐hydroxyprogesterone) and 11β, 17α‐dihydroxypregn‐4‐ene‐3, 20‐dione (11β, 17α‐dihydroxyprogesterone). Thus, either the 21‐hydroxyl group (e.g. 11‐deoxycorticosterone) or the 11β‐hydroxyl group (e.g. 11β‐hydroxyprogesterone) is sufficient for delayed feedback activity. The 11α‐hydroxyl group, e.g. 11α, 17α, 21‐trihydroxypregn‐4‐ene‐3, 20‐dione (11‐epicortisol) renders the steroid inactive on both feedback mechanisms.
18, 21‐Dihydroxypregn‐4‐ene‐3, 20‐dione (18‐hydroxydeoxycorticosterone) was found to be the only steroid that is secreted by the adrenal gland of the rat in quantities sufficient to cause exaggeration of the stress‐induced release of corticotrophin. This steroid has been implicated as a possible hypertensive agent, and its role in the control of corticotrophin secretion is discussed here.
SELECTIVE RESERPINE‐INDUCED SUPERSENSITIVITY OF THE POSITIVE INOTROPIC AND CHRONOTROPIC RESPONSES TO ISOPRENALINE AND SALBUTAMOL IN GUINEA‐PIG ISOLATED ATRIA
Authors: BROADLEY K.J. , LUMLEY P. 
Published: July 2012

Dose‐response curves for the positive inotropic and chronotropic responses to isoprenaline were obtained in atria from untreated guinea‐pigs and those receiving various reserpine pretreatments.
Tension responses were unaffected, whereas rate responses were depressed by the lowest dose of reserpine (0.05 mg/kg i.p. at 24 hours).
With larger 24 h doses and a 3 day pretreatment, the rate and tension dose‐response curves were progressively displaced to the left, indicating supersensitivity which was greater for tension at each pretreatment.
No supersensitivity to histamine or Ca2+ could be detected, leading to the conclusion that it was selective for the β‐adrenoceptor agonists possibly at the receptor level.
As an indication of the adrenergic neurone depleting effectiveness of each reserpine dosage, preparations were exposed to test doses of β‐phenylethylamine.
Salbutamol was a partial agonist in untreated atria, the maximum rate (63.3%) and tension (10.0%) responses being less than those for isoprenaline. In atria from reserpine pretreated animals the supersensitivity was revealed as an increase of this maximum compared with isoprenaline.
The significance of this observation in relation to the possible mechanism of the supersensitivity is discussed.
NICOTINE STIMULATES PROSTAGLANDIN FORMATION IN THE RABBIT HEART
Authors: WENNMALM Å. 
Published: July 2012

Rabbit isolated hearts were perfused according to Langendorff with Tyrode solution. Prostaglandin‐like substances (PLS) in the effluent were purified and assayed on the rat stomach strip. Noradrenaline (NA) in the effluent was assayed fluorimetrically.
Infusion of nicotine (1 μm‐50 μm) caused a dose‐dependent, brief increase, from 1.2 ± 0.4 to maximally 8.3 ± 2.1 ng/min, in the outflow of PLS from the heart. The increase was abolished by pretreatment of the heart with indomethacin.
Activation of nicotinic receptors in the heart with acetylcholine (ACh, 200 μm) in the presence of atropine (1 μm) also elicited an increase in the release of PLS. This release was smaller than that caused by nicotine.
Nicotine (50 μm) and ACh (200 μm) in the presence of atropine (1 μm) each caused a pronounced but brief release of NA into the effluent. There was no evident correlation between the ability of the drugs to cause release of PLS on the one hand, and NA on the other.
It is concluded that nicotine acts as a direct stimulus for the synthesis of prostaglandins in the rabbit heart.
ACCUMULATION OF RADIOACTIVE CARDIAC GLYCOSIDES BY VARIOUS BRAIN REGIONS IN RELATION TO THE DYSRHYTHMOGENIC EFFECT
Authors: DUTTA S. , MARKS B.H. , SCHOENER E.P. 
Published: July 2012

Ouabain was administered at a loading dose of 3 μg/kg followed by an infusion at a rate of 1 μg kg−1 min−1 in order to produce severe dysrhythmia in dogs within 60 minutes. Similarly, digitoxin at a loading dose of 9 μg/kg followed by an infusion at a rate of 3 μg kg−1 min−1 was administered to compare its effect with that of ouabain.
During the 60 min experimental period, the plasma concentrations gradually rose with the continuous infusion of these drugs. However, in comparison to the 60 min plasma value of 119 ± 20 pmol/ml for ouabain and 177 ± 68 pmol/ml for digitoxin, the cerebrospinal fluid (CSF) concentrations for these drugs at this time were less than 5 pmol/ml.
Upon termination of the experiment at 60 min it was found that kidney, liver, heart, adrenal, and the non‐neural tissue in the brain such as pituitary and choroid plexus concentrated ouabain and digitoxin to give high tissue to plasma ratios. However, various neural areas of the brain (cerebellum, mesencephalon, hypothalamus, pons, and medulla) showed no preferential localization or uptake of these two glycosides.
Concentration of ouabain and digitoxin by the choroid plexus does not seem to affect the ionic composition of the CSF.
It was concluded that sampling the large areas of neural tissue listed above could provide no evidence for local accumulation of digitalis glycosides that might account for a central nervous system origin of digitalis‐induced cardiac arrhythmias.
DIFFERENTIATION OF METABOLIC ADRENOCEPTORS
Authors: LOAKPRADIT T. , LOCKWOOD R. 
Published: July 2012

Cardiovascular and metabolic responses to intravenous infusion of isoprenaline were measured in fasted, anaesthetized cats.
Isoprenaline (0.2 μg kg−1 min−1 for 15 min) decreased diastolic blood pressure and increased heart rate, blood glucose, blood lactate and plasma free fatty acids.
Oxprenolol (0.5 mg/kg) antagonized all cardiovascular and metabolic effects of isoprenaline non‐selectively.
Para‐oxprenolol (0.25 mg/kg) and practolol (4 mg/kg) antagonized the effects of isoprenaline on heart rate and free fatty acids selectively.
H 35/25 ((1‐(4‐methylphenyl)‐2‐isopropyl aminopropanol) hydrochloride, 3 mg/kg) antagonized the effects of isoprenaline on blood pressure, glucose and lactate selectively.
It is concluded that metabolic adrenoceptors are differentiated into subtypes similar to those mediating cardiostimulation and vasodilatation.
ROLE OF 5‐HYDROXYTRYPTAMINE IN MORPHINE‐, PETHIDINE‐, AND METHADONE‐INDUCED HYPOTHERMIA IN RATS AT LOW AMBIENT AND ROOM TEMPERATURE
Authors: OKA T. 
Published: July 2012

1 The effect of morphine (10 or 20 mg/kg s.c.), pethidine (25 or 50 mg/kg s.c.) or methadone (4 or 8 mg/kg s.c.) on the body temperature of nontreated and p‐chlorophenylalanine‐pretreated rats was studied at room (21 ± 0.2°C) or low ambient (12 ± 0.2°C) temperature.2 Neither pethidine nor smaller doses of morphine and methadone altered the mean rectal temperature of rats kept at room temperature but larger doses of morphine and methadone produced significant hypothermia.3 All narcotic analgesics at doses used in the present investigation produced significant hypothermia in rats maintained in a low ambient temperature. The hypothermia was prevented by naloxone (1 mg/kg s.c.).4 The administration of p‐chlorophenylalanine (PCPA, 320 mg/kg i.p.) 48 h before the narcotic injection prevented the fall in body temperature both at room and low ambient temperature.5 The administration of narcotic analgesics at doses, which when administered by themselves did not alter the body temperature of rats, produced significant hyperthermia in rats pretreated with PCPA.6 When rats pretreated with PCPA were given 5‐hydroxytryptophan (75 mg/kg s.c.) 30 min before narcotic administration, the usual response to narcotics was restored.7 It appears that pethidine and methadone as well as morphine have both hyperthermic and hypothermic actions in rats and that 5‐hydroxytryptamine may be involved in the narcotic‐induced hypothermia not only at room temperature but also at low ambient temperature.
EFFECT OF TWO HEMICHOLINIUMS ON THE DISPOSITION AND DISTRIBUTION OF ENDOGENOUS FREE CHOLINE IN ANAESTHETIZED RABBITS
Authors: GARDINER J.E. , GWEE M.C.E. 
Published: July 2012

1 The effects of hemicholinium no. 3 (HC‐3) and its p‐terphenyl analogue (TPHC‐3) on the disposition and distribution of free choline were studied in rabbits under pentobarbitone anaesthesia. Free choline was determined by bioassay.2 The respiration of animals given 0.35 μmol/kg of HC‐3 was hardly affected; however, 4 out of 6 rabbits given the same dose of TPHC‐3 exhibited varying degrees of respiratory impairment. All animals that received 2 injections (1 h apart) of either HC‐3 (1.4 μmol/kg) or TPHC‐3 (0.7 μmol/kg) developed respiratory difficulty about 1 h after the second injection.3 The respiratory distress was accompanied by a 2 to 15‐fold rise in plasma choline concentration. This rise has been attributed to hypoxia.4 In experiments in which choline has been infused it was observed that HC‐3 could impair the animal's ability to dispose of exogenous choline. In control rabbits neither HC‐3 nor TPHC‐3 produced changes in plasma choline concentrations unless the respiration was depressed.5 Either HC‐3 or TPHC‐3 (both at 0.35 μmol/kg) significantly (P < 0.05) reduced the kidney choline concentration by 40% and 30% respectively; both hemicholiniums raised the lung choline concentration by about 35%. Only TPHC‐3 caused a significant rise (40%) in liver choline. The choline concentrations in other tissues were unaffected by the hemicholiniums.
THE EFFECTS OF MORPHINE ON THE ACCUMULATION OF HOMOVANILLIC AND 5‐HYDROXYINDOLEACETIC ACIDS IN THE CHOROID PLEXUS OF RATS
Authors: HUANG JEN‐TZAW , WAJDA ISABEL J. 
Published: July 2012

1 Choroid plexus obtained from the lateral ventricles of the rat actively accumulated homovanillic acid (HVA) and 5‐hydroxyindoleacetic acid (5‐HIAA).2 Morphine 5 × 10−6 M to 5 × 10−4 M potentiated 5‐HIAA accumulation but did not affect HVA accumulation. Levorphanol and dextrorphan had little effect.3 Naloxone at high concentrations inhibited both HVA and 5‐HIAA accumulation.4 Glutamic acid, glycine, and arginine also decreased 5‐HIAA accumulation, but lysine, tryptophan, and aspartic acid had no effect.5 Probenecid, naloxone, arginine, glycine, and tryptophan blocked the increase of 5‐HIAA accumulation induced by morphine.6 Acute or chronic morphine treatment did not increase the accumulation of 5‐HIAA.7 These results suggest that the increase of 5‐HIAA or HVA in brain by morphine is not due to the inhibition of the elimination of these metabolites from the choroid plexus.
EFFECTS OF GUANETHIDINE ON HISTAMINE RELEASE DURING REFLEX VASODILATATION IN THE DOG
Authors: CONDORELLI M. , RASETTI G. , RENGO F. , RICCIARDELLI B. , SACCÀ L. , TRIMARCO B. , VOLPE M. 
Published: July 2012

1 The effects of guanethidine pretreatment on the release of [14C]‐histamine during the reflex vasodilatation induced in the atropinized gracilis muscle by rapid intravenous administration of noradrenaline, were studied in dogs.2 After guanethidine treatment the haemodynamic reflex response was completely abolished and no appreciable modification of [14C]‐histamine release from the gracilis muscle following intravenous noradrenaline was observed.3 These results suggest the hypothesis that the withdrawal of the sympathetic discharge represents the mechanism of histamine release during the reflex vasodilatation. Therefore, guanethidine would suppress both the passive and the histaminergic component of the baroreceptor reflex through the abolition of the sympathetic tone.