bluuebunny/crossref_metadata_2025_split huggingface dataset:
INTERACTIONS BETWEEN THE EFFECTS OF α‐ AND β‐ADRENOCEPTOR AGONISTS AND ADENINE NUCLEOTIDES ON THE MEMBRANE POTENTIAL OF CELLS IN GUINEA‐PIG LIVER SLICES
Authors: JENKINSON D.H. , KOLLER KARIN 
Published: July 2012

The β‐adrenoceptor agonist isoprenaline normally causes only a small and inconsistent increase in the membrane potential of cells in guinea‐pig liver slices, in contrast to the large hyperpolarizations seen with α‐agonists. However, after a selective α‐adrenoceptor agonist has been applied, the response to isoprenaline becomes greatly enhanced.
Simultaneous application of small doses of an α‐ and a β‐agonist produce hyperpolarizations larger than the sum of the responses to each agent alone.
These interactions occur with a range of sympathomimetic amines, including some which are not substrates for various processes for the uptake and inactivation of catecholamines.
Hyperpolarizations caused by externally applied cyclic adenosine‐3′,5′‐monophosphate (cyclic AMP) also become larger after application of an α‐agonist.
The adenine nucleotides adenosine 5′‐diphosphate (ADP) and adenosine 5′‐triphosphate (ATP) hyperpolarize guinea‐pig liver cells in the dose range 0.1‐1.0 mm. This response is not increased after an α‐agonist. However, ADP and ATP are themselves able to enhance the response to β‐agonists.
These interactions between α‐agonists, β‐agonists and adenine nucleotides seem to involve steps subsequent to receptor activation. Changes in the intracellular actions of cyclic AMP may be concerned.
PRODUCTION OF PROSTAGLANDINS BY THE PSEUDOPREGNANT RAT UTERUS, in vitro, AND THE EFFECT OF TAMOXIFEN WITH THE IDENTIFICATION OF 6‐KETO‐PROSTAGLANDIN F1α AS A MAJOR PRODUCT
Authors: FENWICK LINDA , JONES R.L. , NAYLOR B. , POYSER N.L. , WILSON N.H. 
Published: July 2012

Prostaglandin production by rat uterus homogenates has been studied, in vitro, on days 2 to 13 of pseudopregnancy.
The highest production of prostaglandins occurred on day 5.
The amounts of prostaglandins F and D formed were higher than the amounts of prostaglandin E on every day studied.
The ratios of prostaglandins F and D to prostaglandin E produced steadily decreased up to day 6. It then increased with the highest values occurring between days 10 and 13.
Progesterone levels in peripheral plasma increased rapidly from days 2 to 5, remained high up to day 9, then steadily decreased between days 10 and 13.
The anti‐oestrogenic drug, tamoxifen administered on day 2, significantly inhibited the increase of prostaglandin production which occurred on day 5. Prostaglandin E production was inhibited more than the production of prostaglandins F and D.
Analysis of the uterine extracts by gas chromatography and mass spectrometry showed prostaglandin F2α, F1α (in trace amounts), E2 and D2 to be present.
The major product detected was 6‐keto‐prostaglandin F1α. Its identification forms an addendum to the paper.
Also present as a major product was 6(9)‐oxy‐11,15‐dihydroxyprosta‐7,13‐dienoic acid.
EFFECTS OF DIBUTYRYL CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE AND THEOPHYLLINE ON THE BULLFROG SYMPATHETIC GANGLION CELLS
Authors: AKASU T. , KOKETSU K. 
Published: July 2012

1 Effects of dibutyryl cyclic adenosine 3′,5′‐monophosphate (dibutyryl cyclic AMP) and theophylline on bullfrog sympathetic ganglion cells were examined in order to test the hypothesis that cyclic AMP is essential for the generation of slow inhibitory postsynaptic potentials (i.p.s.ps) in these cells.2 In the absence or presence of theophylline, dibutyryl cyclic AMP did not hyperpolarize but rather tended to depolarize ganglia that were hyperpolarized by adrenaline.3 Theophylline augmented neither the P‐potential (slow i.p.s.p.) nor adrenaline‐induced hyperpolarization.4 Thus, cyclic AMP does not seem to be essential for the generation of the slow i.p.s.p., at least in amphibian sympathetic ganglion cells.
ANAPHYLACTIC REACTIONS TO ENDOTOXIN IN GUINEA‐PIG TISSUES: RELATIONSHIP TO ENDOTOXIN TOXICITY
Authors: McLEAN A.J. 
Published: July 2012

1 A lipopolysaccharide extract of Escherichia coli 026:B6 cells (026:B6(B) endotoxin) was shown to be toxic to normal adult guinea‐pigs.2 The agent had no action on isolated preparations of ileum and heart taken from normal adult guinea‐pigs.3 Ileal segments from animals actively immunized against 026:B6(B) endotoxin showed dose‐dependent contractions when exposed to endotoxin. Desensitization phenomena were demonstrated.4 Reactivity of 026:B6(B) endotoxin was transferred to isolated preparations of ileum and heart from normal animals by passive transfer of immune serum.5 Tissue responses to 026:B6(B) were associated with release of ileal spasmogen into the bath medium. Mepyramine blocked the effects of this spasmogen at bath concentrations which caused little change in ileal responses to carbachol.6 It is concluded that E. coli endotoxin can elicit anaphylactic reactions, and that this process may potentiate endotoxin toxicity in sensitized animals. However, endotoxin toxicity in guinea‐pigs does not appear to depend on this kind of allergic process.
COMPARISON OF THE EFFECTS OF CAFFEINE AND A 2‐ALKYL‐1,2,3‐BENZOTRIAZINIUM IODIDE ON FROG RECTUS ABDOMINIS
Authors: MUIR C.K. , SCOTT N.C. 
Published: July 2012

1 The mode of action of 2‐n‐propyl‐4‐p‐tolylamino‐1,2,3‐benzotriazinium iodide (TnPBI), which induced contractures of frog rectus abdominis muscle, was investigated.2 TnPBI caused contractures of frog rectus abdominis when the muscle had been depolarized with potassium chloride.3 Experiments with TnPBI and caffeine in calcium‐free Ringer suggested that both compounds produce contractures by releasing intracellular bound calcium.4 It is suggested that at least two calcium stores are involved, one of which is sensitive to caffeine while both are sensitive to TnPBI.
OLFACTORY BULB ABLATION IN THE RAT: BEHAVIOURAL CHANGES AND THEIR REVERSAL BY ANTIDEPRESSANT DRUGS
Authors: van RIEZEN H. , SCHMIEDEN H. , WREN ALLISON F. 
Published: July 2012

1 The effects of bilateral olfactory bulbectomy, sham‐operation and inducement of peripheral anosmia were studied on locomotor activity, passive avoidance acquisition and irritability.2 Bulbectomized rats were hyperactive, deficient at learning a step‐down passive avoidance response and hyperirritable. Peripheral anosmia, induced by intranasal infusion of ZnSO4 solution resulted in no behavioural changes.3 Chronic pretreatment with amitriptyline (3 and 10mg/kg) and a tetracyclic antidepressant mianserin (Org GB 94, 5 and 15 mg/kg) reversed the hyperactivity and reduced the learning deficit of bulbectomized rats. These drugs had no significant effects on sham‐operated animals.4 Neither amitriptyline nor mianserin reduced the exaggerated responses of bulbectomized rats to external stimuli.5 (+)‐Amphetamine (1 and 3 mg/kg) accelerated the acquisition of the passive avoidance response, greatly enhanced the locomotor activity and slightly increased the irritability score of both sham‐operated and bulbectomized rats.6 Chlorpromazine (1 and 3 mg/kg) and chlordiazepoxide (10 mg/kg) significantly reduced the acquisition, locomotor activity and irritability of experimental and control rats.7 Lithium sulphate (1 and 3 mg/kg) had no effect on activity or irritability but produced a small impairment in acquisition of bulbectomized rats.8 It is concluded that the reversal by antidepressant drugs of the behavioural syndrome seen after olfactory bulb ablation could constitute a new model for the detection of this group of centrally acting compounds.
AGONIST AND ANTAGONIST PROPERTIES OF BUPRENORPHINE, A NEW ANTINOCICEPTIVE AGENT
Authors: COWAN A. , LEWIS J.W. , MACFARLANE I.R. 
Published: July 2012

1 Buprenorphine is a highly lipophilic derivative of oripavine. In rodent antinociceptive assays (writhing, tail pressure), buprenorphine had an action which was rapid in onset and of long duration; it was 25‐40 times more potent than morphine after parenteral injection and 7‐10 times more potent after oral administration.2 The log dose‐response relationship for buprenorphine was curvilinear in mouse and rat tail flick tests with the antinociceptive effect decreasing at higher, non‐toxic doses.3 Tolerance developed to the antinociceptive activity of buprenorphine in mice.4 No signs of abstinence were observed on naloxone challenge or after abrupt withdrawal in monkeys receiving buprenorphine chronically for one month.5 Buprenorphine antagonized the antinociceptive actions of morphine in mouse and rat tail flick tests but was an ineffective antagonist in the rat tail pressure test.6 Buprenorphine precipitated signs of abstinence in morphine‐dependent mice and monkeys but not in morphine‐dependent rats.7 Buprenorphine produced Straub tails in mice. This effect was not antagonized when the animals were pretreated with naloxone. However, in the rat tail pressure test high doses of diprenorphine antagonized established antinociceptive effects of buprenorphine.8 It is concluded that buprenorphine represents a definite advance in the search for a narcotic antagonist analgesic of low physical dependence potential.
THE UPTAKE AND OVERFLOW OF RADIOLABELLED β‐ADRENOCEPTOR BLOCKING AGENTS BY THE ISOLATED VAS DEFERENS OF THE RAT
Authors: LEWIS M.J. 
Published: July 2012

1 A comparison of uptake into and overflow from the isolated vas deferens of the rat has been made between [3H]‐noradrenaline ([3H]‐NA), [14C]‐D‐sorbitol and three radio‐labelled β‐adrenoceptor blocking agents, [14C]‐practolol, [14C]‐(+)‐propranolol and [3H]‐penbutolol.2 The accumulation of [3H]‐NA after 30 min incubation was reduced by desmethylimipramine (DMI) 1 × 10−8M and was also reduced in vasa from rats pretreated with 6‐hydroxydopamine (6‐OHDA). This was not so with [14C]‐D‐sorbitol.3 6‐OHDA pretreatment of the rats reduced the uptake of f [3H]‐penbutolol after 30 min incubation but not that of [14C]‐propranolol or [14C]‐practolol. DMI 1 × 10−8M did not alter the tissue uptake of [14C]‐propranolol, [14C]‐practolol or [3H]‐penbutolol.4 Electrical stimulation of vasa preloaded with [3H]‐NA caused a significantly greater increase in [3H]‐NA overflow than during the resting, unstimulated periods. No such increase in overflow was observed with [14C]‐sorbitol or any of the three β‐adrenoceptor blocking agents used.5 The β‐adrenoceptor blocking agent penbutolol was shown to possess adrenergic neurone blocking activity in the isolated vas deferens of the rat.6 It is concluded that any effect that practolol or (+)‐propranolol have on noradrenergic neurones is brought about without the need for these drugs to gain access to the interior of the neurone.
THE EFFECT OF SYSTEMICALLY AND TOPICALLY APPLIED DRUGS ON ULTRAVIOLET‐INDUCED ERYTHEMA IN THE RAT
Authors: LAW E. , LEWIS A.J. 
Published: July 2012

Exposure of the skin of rats to u.v. light (>295 nm) for 30 s or longer elicited a delayed erythema response, the rate of onset increasing with the period of irradiation. The erythema was still present at 24 h and was replaced by scab formation in 48 hours.
Both topically applied steroidal and non‐steroidal anti‐inflammatory drugs reduced the erythema formation when administered immediately after u.v. exposure. Propyl gallate, an antioxidant with sun screening properties in man, also possessed topical anti‐erythemic activity.
Both steroidal and non‐steroidal anti‐inflammatory drugs, systemically administered 1 h before u.v. exposure, reduced the erythema. However, the steroidal compounds were less effective than the nonsteroids and reduced the intensity of erythema by less than 50%. Antagonists of 5‐hydroxytryptamine (5‐HT) reduced the erythema but several other drugs with different pharmacological activities were ineffective.
Neither topical nor systemic treatments of any of the drugs examined suppressed the scab formation at 48 hours.
These results and those using other selective blocking agents indicate that in the mediation of the erythema reaction prostaglandins may play a major role and 5‐HT perhaps a minor one but that H1 histamine receptors and α‐ and β‐adrenoceptors have no significant role.
THE SYMPATHOMIMETIC ACTIVITY OF FENFLURAMINE HYDROCHLORIDE ON RAT VAS DEFERENS
Authors: MOTTRAM D.R. , WADHWANI D. 
Published: July 2012

The peripheral, pharmacological effects of the anorexigenic agent, fenfluramine hydrochloride, have been investigated on rat isolated vas deferens.
Characteristic spiked contractions were observed within 2 to 3 min after exposure to fenfluramine; these contractions reached a rate of around 13 per min and were of variable height.
Pre‐treatment of vasa with the indirectly acting sympathomimetic amine, tyramine, greatly reduced both the height and rate of contraction induced by fenfluramine.
The uptake inhibitor, desipramine, required a concentration in excess of 10 μM to affect fenfluramine‐induced contractions. Effects of desipramine on fenfluramine contractions were of equal magnitude whether desipramine was administered before fenfluramine or at the height of the fenfluramine‐induced contractions.
Pre‐treatment with debrisoquine (0.5 mM), reduced the contractions in response to fenfluramine over a period of time.
Fenfluramine, added to vasa from rats which had been injected intraperitoneally with 5 mg/kg reserpine 24 h and 48 h previously, failed to induce its characteristic contractions.
It is concluded that fenfluramine can be classed as an indirectly acting sympathomimetic amine on peripheral adrenergic nerve terminals.
EVIDENCE FOR A VISCERAL SMOOTH MUSCLE ABNORMALITY IN OKAMOTO SPONTANEOUS HYPERTENSION
Authors: ALTMAN J. , DA PONTE F. , WORCEL M. 
Published: July 2012

In order to discover whether the changes in reactivity are related to the primary cause of hypertension in spontaneously hypertensive rats (SHR) or are just an adaptation induced by the high arterial blood pressure we tested the contractile response of a visceral smooth muscle from such rats.
Longitudinal strips of the fundus from 20 week old male and female SHR and Wistar normotensive (NW) rats were used. Dose‐response curves to Ba2+ in SHR strips were displaced to the right as compared to NW rats. Maximal responses were identical. Male SHR fundus strips contracted much more with Sr2+ (SHR: 42 ± 3% of maximum response to Ba2+, n= 10; NW: 19 ± 4%, n= 10, P<0.01) than NW strips. There was no difference in the response to both BaCl2 and SrCl2 between female SHR and NW fundus strips, and MnCl2 and LaCl3 were relaxant in all cases.
Dose‐response curves to Ca2+ of depolarized SHR and NW fundus strips were obtained and the effect of diazoxide on Ca2+ contractions was observed. The contractile action of Ca2+ in depolarized preparations was enhanced in both male and female SHR strips. The effect of diazoxide was more marked in SHR strips than in NW fundus strips.
SHR fundus smooth muscle shows the same modification of reactivity to Ba2+, Sr2+, Ca2+ and diazoxide that was previously described in arterial smooth muscle. This indicates that the cellular modification responsible for the increase of vascular tonus in SHR is not an adaptive reaction to high blood pressure. The differences between female SHR and male SHR responses are not unexpected, considering the natural evolution of hypertension in Okamoto rats which is milder in the female.
EFFECT OF INTRAHYPOTHALAMIC PHENTOLAMINE ON HYPOTHERMIA PRODUCED BY PERIPHERAL NORADRENALINE IN THE PIGEON
Authors: HISSA R. , PYÖRNILÄ A. 
Published: July 2012

The effect of intrahypothalamic phentolamine (1 and 2 μl of a 10 μg/μl solution) on hypothermia induced by intramuscular injection of noradrenaline (NA, 2 mg/kg) at different times (2, 10, 20 min) after phentolamine was investigated in pigeons.
Administration of phentolamine shortly before NA was shown to attenuate hypothermic responses to NA.
It is suggested that the attenuation is due to blockade of central hypothermic effects of intramuscular NA.
The mapping of injection sites in the brains was carried out.
LIGAND BINDING TO MUSCARINIC RECEPTORS IN INTACT LONGITUDINAL MUSCLE STRIPS FROM GUINEA‐PIG INTESTINE
Authors: WARD DAWN , YOUNG J.M. 
Published: July 2012

The binding of ligands to muscarinic receptors in intact longitudinal muscle strips from guinea‐pig small intestine has been determined by measuring the inhibition of the irreversible binding of [3H]‐propylbenzilylcholine mustard ([3H]‐PrBCM).
The IC50 values for inhibition of [3H]‐PrBCM binding by a given ligand were generally higher in intact strips than those reported for broken‐cell preparations. This effect is probably due, at least in part, to the presence of an access‐limitation factor in the kinetics of the irreversible binding of [3H]‐PrBCM to the intact tissue.
The mean Hill coefficients for antagonist binding approached unity, but those for strong agonists were significantly less than unity. There was, with the possible exceptions of hexyltrimethylammonium and oxotremorine, reasonably good agreement with the Hill coefficients reported for brain homogenates.
THE EFFECTS OF PENTOBARBITONE AND CHLORALOSE ANAESTHESIA ON THE VAGAL COMPONENT OF BRONCHOCONSTRICTION PRODUCED BY HISTAMINE AEROSOL IN THE ANAESTHETIZED DOG
Authors: JACKSON D.M. , RICHARDS I.M. 
Published: July 2012

Total lung resistance (RL) and dynamic lung compliance (Cdyn) were measured in dogs anaesthetized with pentobarbitone or chloralose and subjected to aerosols of histamine during 4 successive inspirations.
Histamine caused concentration‐dependent increases in RL and decreases in Cdyn. A significant vagal component was involved, but only when chloralose was employed and then only in the RL response.
The resting values of RL and Cdyn were similar regardless of which anaesthetic was used and remained essentially the same if the vagi were cooled.
Electrical stimulation of the efferent vagi caused large increases in RL of dogs given chloralose and these effects were attenuated by the administration of pentobarbitone. Such stimulation was relatively ineffective in dogs given pentobarbitone alone.
In vitro, electrical field stimulation caused contractions of dog trachealis muscle. The responses were reduced by pentobarbitone in concentrations approximating to plasma levels in the anaesthetized dogs (1 to 5 × 10−4 M), but the effects of exogenous acetylcholine were unaltered. The inhibition was dose‐dependent, reversed by washing and unaltered by hexamethonium.
The results suggest that pentobarbitone inhibits the vagal component of histamine‐induced bronchoconstriction in the dog by an action on the efferent pathway. Furthermore, pentobarbitone acts either by blocking transmission along postganglionic parasympathetic nerves or by preventing the release of acetylcholine from the nerve endings in the lung.
THE EFFECT OF ATROPINE ON ACID SECRETION STIMULATED BY ACETYLCHOLINE, HISTAMINE AND GASTRIN IN THE ISOLATED WHOLE STOMACH OF THE RAT
Authors: BUNCE K.T. , MARSH GILLIAN F. , PARSONS M.E. 
Published: July 2012

An isolated stomach preparation from immature rats has been used to study the effect of atropine on gastric acid secretion.
The acid secretory response to acetylcholine was not inhibited by atropine at a concentration of 0.3 μM. Concentrations of atropine of 1 to 3 μM produced a measurable inhibition of acid secretion, and a concentration of atropine of 10 μM caused a complete block of acid secretion which could not be surmounted by high concentrations of acetylcholine.
The acid secretory response to histamine was not inhibited by concentrations of atropine of up to 1 mM.
Concentrations of atropine of 1 μM and 10 μM did not inhibit gastrin‐stimulated acid secretion, although a significant inhibition of acid output was observed with atropine at concentrations of 0.1 mM and 1 mM.
These findings are discussed in relation to the role of cholinergic mechanisms in the control of gastric acid secretion.
ELECTROCORTICAL CHANGES INDUCED BY THE PERFUSION OF NORADRENALINE, ACETYLCHOLINE AND THEIR ANTAGONISTS DIRECTLY INTO THE DORSAL RAPHÉ NUCLEUS OF THE CAT
Authors: KEY B.J. , KRZYWOSKINSKI L. 
Published: July 2012

The electrocortical changes induced by the perfusion of drugs directly into the dorsal raphé nucleus of the cat encéphale isolé preparation have been studied.
(−)‐Noradrenaline (NA), (−)‐adrenaline, or (−)‐isoprenaline (Isop) produced intermittent or sustained electrocortical desynchronization during the perfusion period.
These changes were markedly attenuated or completely abolished by the prior perfusion of (±)‐sotalol or (−)‐propranolol, but not by equimolecular concentrations of (+)‐propranolol.
The effects of NA or Isop were also blocked by phentolamine, whereas phenoxybenzamine either potentiated the responses to NA and Isop or mimicked the effects of these catecholamines.
The effect of dopamine was similar to that induced by NA, but could not be elicited at all of the perfusion sites where NA was effective. It could be blocked by (±)‐sotalol or (−)‐propranolol and also by the prior perfusion of fusaric acid.
Acetylcholine (ACh) increased, or initiated, electrocortical synchronization. These effects could be antagonized by sensory stimulation, the prior perfusion of atropine, or the simultaneous perfusion of NA at the same site.
Lignocaine, induced prolonged electrocortical desynchronization, behavioural alerting and an increased responsiveness to sensory stimulation.
The results have been discussed in relation to the possible involvement of inhibitory β‐adrenoceptors and facilitatory cholinoceptors (muscarinic) in the functioning of the dorsal raphé nucleus.
PLASMA CONCENTRATIONS AND CARDIOTOXIC EFFECTS OF DESIPRAMINE AND PROTRIPTYLINE IN THE RAT
Authors: BIANCHETTI G. , BONACCORSI AURORA , CHIODAROLI A. , FRANCO R. , GARATTINI S. , GOMENI R. , MORSELLI P.L 
Published: July 2012

Desipramine and protriptyline were administered to anaesthetized rats by two consecutive intravenous infusions in order to obtain a peak level (first infusion) followed by lower steady state concentrations (second infusion) (Wagner, 1974). Theoretical plasma level time courses were confirmed experimentally.
Desipramine and protriptyline were measured in atria and ventricles. Increasing infusion rates led to proportional increases in plasma and atrial concentrations. The tissue/medium ratio ranged from 57 to 21 for desipramine and from 43 to 11 for protriptyline according to the time of determination during infusions.
Heart rate changes, deviation of the electrical axis of the heart and prolongation of atrioventricular conduction were recorded at fixed times during infusion.
Positive chronotropic effects were noted at plasma concentrations ranging from 0.035 to 0.1 μg/ml for desipramine and from 0.04 to 1.2 μg/ml for protriptyline. At higher plasma concentrations the positive chronotropic effect decreased and bradycardia developed. Both drugs induced right rotation of the electrical axis of the heart. Threshold plasma levels giving 40° rotation were 1.35 μg/ml (desipramine) and 1.75 μg/ml (protriptyline). Atrioventricular conduction was prolonged at threshold plasma concentrations of 2.2 μg/ml for desipramine and 3.6 μg/ml for protriptyline.
Desipramine is more cardiotoxic than protriptyline. This difference is discussed in relation to the plasma and heart concentration of the two drugs.