bluuebunny/crossref_metadata_2025_split huggingface dataset:
INHIBITION BY THE TETRAMINE DISULPHIDE, BENEXTRAMINE, OF CARDIAC CHRONOTROPIC HISTAMINE H2‐RECEPTOR‐MEDIATED EFFECTS
Authors: BELLEAU B. , BENFEY B.G. , BENFEY T.J. , MELCHIORRE C. 
Published: July 2012

Benextramine (N,N'‐bis[o‐methoxybenzylamino)‐n‐hexyl]cystamine), which irreversibly blocks α‐adrenoceptors and does not inhibit the H1‐receptor‐mediated contractile effect of histamine on guinea‐pig isolated ileum, also did not inhibit the H1‐receptor‐mediated inotropic effect of histamine on guinea‐pig isolated atrium.
Benextramine irreversibly inhibited the H2‐receptor‐mediated chronotropic effect of histamine on guinea‐pig isolated atrium.
Since its combination with the competitive H2‐receptor blocking drug cimetidine had an additive blocking effect, benextramine appears to act directly on the chronotropic H2‐receptor.
EFFECTS OF DIVALENT CATIONS AND NORMORPHINE ON SPONTANEOUS EXCITATORY JUNCTION POTENTIALS IN THE MOUSE VAS DEFERENS
Authors: ILLES P. , NORTH R.A. 
Published: July 2012

Excitatory junction potentials (e.j.ps) occurring spontaneously or evoked by nerve stimulation were recorded intracellularly from smooth muscle cells of the mouse isolated vas deferens.
The amplitude of the evoked e.j.ps and the amplitude and frequency of spontaneous e.j.ps were measured before and during application of normorphine or solutions which might be expected to change the influx of calcium ions into the nerve terminals.
Spontaneous e.j.ps could be recorded even in solutions which contained tetrodotoxin (1 μm), no added calcium and EGTA (1 mm). A four fold increase in calcium concentration from 1.25 to 5 mm greatly increased the amplitude of the evoked e.j.ps but had no effect on the amplitude or frequency of the spontaneous e.j.ps.
Magnesium (12 mm) and cobalt (4 mm) both greatly reduced the evoked e.j.ps and also reduced the frequency of spontaneous e.j.ps.
Normorphine (2 μm) reduced the amplitude of the evoked e.j.p. by 70% but had no effect on the amplitude or frequency of spontaneous e.j.ps.
It is suggested that normorphine inhibits noradrenaline secretion from nerve varicosities by a mechanism different from that of magnesium and cobalt. One possibility is a block of action potential propagation along varicose fibres.
HYPOTHALAMIC CATECHOLAMINES AND TOLERANCE FOR SEVERE COLD IN ETHANOL‐TREATED GUINEA‐PIGS
Authors: HUTTUNEN PIRKKO 
Published: July 2012

The effect of ethanol (2g/kg) on hypothalamic catecholamines in guinea‐pigs kept at room temperature (20°C) and in severe cold (—20°C) for 1.5 h was determined. Serum glucose, triacylglycerols and free fatty acids (FFAs), glycogen in liver and skeletal muscle and total lipid and triacylglycerols in the interscapular adipose tissue were also determined.
Ethanol increased the noradrenaline and adrenaline content of the hypothalamus at 20°C and reduced the rectal temperature by about 2°C. The hypothalamic noradrenaline content of the ethanol‐treated guinea‐pigs exposed to cold, in which the fall in rectal temperature was about 8°C, was higher than in the controls, whose rectal temperature decreased only by about 2°C.
Cold exposure increased FFA concentration in serum and reduced skeletal muscle glycogen and serum glucose concentrations in both groups, but no significant differences were found in the carbohydrate and lipid values between the groups at — 20°C.
It is possible that the diminished cold tolerance in the ethanol‐treated guinea‐pigs might be due, at least in part, to the effect of ethanol on the catecholamines in the hypothalamus.
PRESYNAPTIC EFFECT OF CLONIDINE ANTAGONIZED BY THE TETRAMINE DISULPHIDE, BENEXTRAMINE
Authors: BELLEAU B. , BENFEY B.G. , MELCHIORRE C. 
Published: July 2012

The presynaptic α‐adrenoceptor blocking activity of the newly synthesized α‐adrenoceptor blocking drug, benextramine, was evaluated in the isolated left atrium of the guinea‐pig heart.
High‐voltage stimulation increased the force of contraction of electrically driven atrial strips, presumably by releasing noradrenaline from sympathetic nerve endings. Like phentolamine, benextramine increased the effect of high‐voltage stimulation, presumably by blocking presynaptic α‐adrenoceptors.
Clonidine reduced the effect of high‐voltage stimulation, presumably by stimulating presynaptic α‐adrenoceptors. The inhibitory effect of clonidine was antagonized noncompetitively by benextramine and competitively by phentolamine.
Combined administration of benextramine and phentolamine only resulted in the competitive phentolamine antagonism. Thus phentolamine protected the presynaptic α‐adrenoceptors against benextramine blockade.
DISSOCIATION OF β‐ADRENOCEPTOR‐INDUCED EFFECTS ON AMYLASE SECRETION AND CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE ACCUMULATION
Authors: CARLSÖÖ BENGT , DANIELSSON ÅKE , HENRIKSSON ROGER , IDAHL LARS‐ÅKE 
Published: July 2012

By using a multi‐channel microperifusion system the effects of noradrenaline, the β1‐adrenoceptor agonist prenalterol, and the β2‐selective agonist terbutaline were studied on amylase release and cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) content in rat parotid and guinea‐pig submandibular glands.
Noradrenaline caused significant amylase discharge and cyclic AMP accumulation.
Prenalterol was as effective as noradrenaline in causing amylase release but did not significantly affect the cyclic AMP content.
Terbutaline stimulated cyclic AMP accumulation, but had little effect on amylase secretion.
The present study reveals that there is a dissociation of the β‐adrenoceptor‐induced amylase release and cyclic AMP formation, and that this dissociation may be due to different β‐adrenoceptor subtypes.
THE ACTIONS OF PENTOBARBITONE, PROCAINE AND TETRODOTOXIN ON SYNAPTIC TRANSMISSION IN THE OLFACTORY CORTEX OF THE GUINEA‐PIG
Authors: RICHARDS C.D. 
Published: July 2012

It has been suggested that the depression of excitatory synaptic potentials produced by general anaesthetics can be attributed to a partial blockade of impulse conduction in the terminal branches of axons. This hypothesis has been tested by comparing the actions of pentobarbitone, procaine and tetrodotoxin (TTX) on synaptic transmission in the guinea‐pig olfactory cortex.
Pentobarbitone (0.1–0.3 mm) depressed the evoked synaptic potentials without any significant depression of impulse conduction in the afferent fibres of the lateral olfactory tract (l.o.t.). It had no effect on the electrical excitability of either the l.o.t. axons or the postsynaptic neurones.
Tetrodotoxin (TTX; 1–5 × 10−8 m) slowed conduction of impulses in the l.o.t. and decreased the amplitude of the l.o.t. compound action potential in proportion to the concentration applied. All concentrations of TTX elevated the electrical threshold of the l.o.t. axons and there was evidence to suggest that the threshold of the postsynaptic neurones was also elevated. The synaptic potentials were depressed in direct proportion to the depression of the l.o.t. compound action potential.
Procaine (0.1–0.5 mm) exhibited a pattern of activity intermediate between pentobarbitone and TTX. The most marked effect, seen at all concentrations tested, was a slowing of impulse conduction and a decrease in the electrical excitability of the l.o.t. axons.
It is concluded that general anaesthetics (exemplified by pentobarbitone) depress synaptic transmission by interfering with the processes involved in chemical transmission and not by blocking impulse conduction in the terminal branches of afferent nerves.
STEREOCHEMICAL REQUIREMENTS FOR CENTRAL AND PERIPHERAL MUSCARINIC AND ANTIMUSCARINIC ACTIVITY OF SOME ACETYLENIC COMPOUNDS RELATED TO OXOTREMORINE
Authors: DAHLBOM R. , JENDEN D.J. , RESUL B. , RINGDAHL B. 
Published: July 2012

The enantiomers of some analogues of the central muscarinic agent, oxotremorine, were prepared and investigated for tremorogenic and tremorolytic activity in intact mice and for muscarinic and antimuscarinic activity on the isolated ileum of the guinea‐pig.
The R‐isomers were more potent than the S‐isomers both in vivo and in vitro regardless of whether the compounds are agonists, partial agonists or competitive antagonists.
It is suggested that in the oxotremorine series, agonists and antagonists interact with a common receptor site, in contrast to classical muscarinic antagonists which are believed to bind also to accessory receptor areas, located close to the agonist binding site.
EFFECTS OF IMPROMIDINE, A SPECIFIC H2‐RECEPTOR AGONIST AND 2‐(2‐PYRIDYL)‐ETHYLAMINE, AN H1‐RECEPTOR AGONIST, ON STIMULATION‐INDUCED RELEASE OF [3H]‐NORADRENALINE IN GUINEA‐PIG ISOLATED ATRIA
Authors: RAND M.J. , STORY D.F. , WONG‐DUSTING HELEN 
Published: July 2012

The specific histamine H2‐receptor agonist, impromidine (3–100 nmol/l), increased the rate and force of beating of guinea‐pig isolated atria. These effects were blocked by the H2‐receptor antagonist, cimetidine (30 μmol/l), but not by the H1‐receptor antagonist, mepyramine (0.1 μmol/l).
In atria that had previously been incubated in [3H]‐noradrenaline, impromidine (3–100 nmol/l) had no effect on the resting efflux of radioactivity, but concentrations of 50 and 100 nmol/l significantly increased the efflux induced by electrical stimulation (2 Hz for 10 s) of the intramural sympathetic nerves by approximately 38%; lower concentrations (3, 10 and 25 nmol/l) had no effect.
The effect of impromidine in enhancing stimulation‐induced efflux of radioactivity was abolished by cimetidine (30 μmol/l) and by mepyramine (0.1 μmol/l). It was unaffected by the α‐adrenoceptor antagonist, phentolamine (30 μmol/l).
Impromidine produced some inhibition of the uptake of [3H]‐noradrenaline, but this did not account for the enhancement of the stimulation‐induced efflux of radioactivity, since impromidine (50 nmol/l) still increased release in the presence of cocaine (30 μmol/l).
The specific H1‐receptor agonist, 2‐(2‐pyridyl)‐ethylamine (10–100 μmol/l), increased both the resting and stimulation‐induced efflux of radioactivity. These effects were not blocked by mepyramine (0.1 μmol/l) or the β‐adrenoceptor antagonist, metoprolol (0.1 μmol/l).
The prejunctional inhibitory histamine receptors in guinea‐pig atria are not classifiable into H1‐or H2‐type by the use of relatively specific postjunctional histamine H1‐ or H2‐receptor agonists and antagonists.
DESENSITIZATION BY TERBUTALINE OF β‐ADRENOCEPTORS IN THE GUINEA‐PIG SOLEUS MUSCLE: BIOCHEMICAL ALTERATIONS ASSOCIATED WITH FUNCTIONAL CHANGES
Authors: BUUR T. , CLAUSEN T. , HOLMBERG E. , JOHANSSON U. , WALDECK B. 
Published: July 2012

The effects of adrenaline and terbutaline on cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) content, 22Na‐efflux, 42K‐influx and subtetanic contractions have been assessed in soleus muscles isolated from guinea‐pigs which had been maintained on food with or without terbutaline for 5 days.
Terbutaline and adrenaline increased cyclic AMP content and suppressed subtetanic contractions, and regression analysis indicates a statistically significant correlation between these two effects (P<0.01).
In muscles obtained from terbutaline‐treated animals, the effects of terbutaline and adrenaline on cyclic AMP content, active Na‐K‐transport and subtetanic contractions were all considerably suppressed, but insulin stimulated 22Na‐efflux and affected subtetanic contractions to the same extent as in the muscles obtained from the control group.
The results suggest that terbutaline treatment leads to a reduction in the number of β2‐adrenoceptors in skeletal muscle or an impairment of their function.
The results provide further support for the idea that the effect of adrenaline or insulin on skeletal muscle contractions is the outcome of stimulation of active Na‐K‐transport.
EFFECT OF SULPHASALAZINE ON PULMONARY INACTIVATION OF PROSTAGLANDIN F2α IN THE PIG
Authors: HELLEWELL P.G. , PEARSON J.D. 
Published: July 2012

The metabolism of prostaglandin F2α (PGF2α) 15 nM in 100,000 g supernatant fractions from piglet lung homogenates was inhibited by sulphasalazine with an IC50 value of 25 μm.
The piglet isolated lung perfused with Krebs solution, containing either albumin or Ficoll 70 to prevent oedema and vascular damage, efficiently metabolized PGF2α given as a bolus injection (1 ng in 0.1 ml; 30 nM).
In Krebs solution containing Ficoll 70, sulphasalazine inhibited the pulmonary inactivation of PGF2α in a dose‐dependent manner with an IC50 value of 110 μm. No inhibition of inactivation by sulphasalazine was found when the perfusion fluid contained albumin, which is known to bind this drug effectively.
Analysis of the separated efflux profiles for PGF2α and its metabolites with reference to the dilution curve for an extracellular marker provided evidence that sulphasalazine inhibited PGF2α uptake into lung cells.
We conclude that the effect of sulphasalazine on pulmonary prostaglandin inactivation is primarily due to inhibition of prostaglandin transport, and not to inhibition of prostaglandin metabolism.
AN EXAMINATION OF THE PRE‐ AND POSTSYNAPTIC α‐ADRENOCEPTORS INVOLVED IN NEUROEFFECTOR TRANSMISSION IN RABBIT AORTA AND PORTAL VEIN
Authors: DOCHERTY JAMES R. , STARKE KLAUS 
Published: July 2012

The α‐adrenoceptor agonists, Clonidine and xylazine, reduced and the α‐antagonists, yohimbine and rauwolscine, increased the stimulation‐evoked tritium overflow from rabbit aorta and portal vein pre‐incubated with [3H]‐noradrenaline.
Based on an order of agonist potency of Clonidine > xylazine > phenylephrine and antagonist potency of rauwolscine = yohimbine > prazosin, the presynaptic receptor mediating these effects is of the α2‐type.
In the aorta, stimulation‐evoked contractions were abolished by prazosin (0.1 μm) and potentiated by rauwolscine and yohimbine in concentrations that increased the stimulation‐evoked overflow of tritium.
In the portal vein, prazosin was less potent in reducing, and rauwolscine and yohimbine failed to potentiate, the stimulation‐evoked contraction.
In experiments in which tissues were pre‐exposed to phenoxybenzamine (30 nM) to block some of the postsynaptic α‐receptors, rauwolscine in concentrations that increased stimulation‐evoked tritium overflow, reduced the evoked contraction in the portal vein but not in the aorta.
It is concluded that presynaptic α2‐autoreceptors are present in both tissues and that the postsynaptic α‐receptors which mediate nerve stimulation‐evoked contractions are α1 in the aorta but a mixture of α1 and α2 in the portal vein.
ELECTROPHYSIOLOGICAL AND OTHER EFFECTS ON RABBIT HEARTS OF CCI 22277, A NEW STEROIDAL ANTIARRHYTHMIC DRUG
Authors: CAMPBELL T.J. , WILLIAMS E.M. VAUGHAN 
Published: July 2012

CCI 22277 (methyl 2β‐ethoxy‐2α‐hydroxy‐1 1α‐(3‐methylbutylamino)‐5α‐androstane‐17β‐carboxylate hydrochloride) is an aminosteroid with antiarrhythmic properties in animal models.
It slowed significantly conduction velocity and spontaneous frequency.
CCI 22277 was a local anaesthetic on frog nerve, 62 times more potent than procaine. It greatly reduced the maximum rate of depolarization (MRD) in atria, Purkinje cells and ventricles, and reduced the overshoot potential. The effects were frequency‐dependent and it was concluded that the drug probably delayed recovery from inactivation of fast inward current.
CCI 22277 had no anti‐adrenergic actions, nor did it prolong action potential duration (APD) in any cardiac tissues.
The drug was negatively inotropic, and depressed the positive inotropic responses of atria to increased extracellular calcium.
At high concentrations and at rapid pacing frequency, the action potential plateau disappeared and APD became very short.
It was concluded that CCI is primarily a class I antiarrhythmic drug at low concentration, with additional class IV action at higher concentrations.
EXPERIMENTAL DISSOCIATION OF THE EFFECTS OF PROSTAGLANDINS ON RENAL SODIUM AND WATER REABSORPTION BY CYCLO‐OXYGENASE INHIBITORS IN THE RAT
Authors: BARTOLI ETTMORE , BRANCA GIAN FRANCO , FAEDDA ROSSANA , OLMEO NINA A. , SATTA ANDREA , SOGGIA GIOVANNI 
Published: July 2012

The relative importance of the effect of prostaglandins on renal sodium and water reabsorption was assessed in rats.
Clearance experiments were performed on 24 anaesthetized rats divided into 3 groups. Each group was infused throughout either with Ringer solution at 9 ml/h (Protocol I), or at 3 ml/h (Protocol II) or with hypotonic fluid at 5 ml/h (Protocol III). Clearance periods were performed before and after intravenous injection of indomethacin (5 mg/kg) and then of aspirin (20 mg/kg). The natriuretic response to different degrees of volume expansion was not modified during the action of the inhibitors.
When baseline urine osmolality (Uosm) was high (Protocol II) no further increase occurred in the presence of prostaglandin inhibition. Conversely, Uosm rose from 771 ± 134 to 1356 ± 414 and from 575 ± 245 to 841 ± 407 mosm/kg (P < 0.05) in Protocol I and Protocol III respectively, when antidiuretic hormone secretion was inhibited by the higher degree of volume expansion.
There was a significant correlation between the change in urine flow rate induced by cyclo‐oxygenase inhibitors and the attendant variations in Na excretion, r = 0.42, n = 41, P < 0.01.
Thus, prostaglandins affect Na loss during saline load as a side effect of their action on water permeability. They could play an important role in volume depletion by counterbalancing the large secretion rate of renal vasoconstrictors.
THE EFFECT OF NALOXONE ON OPIOID‐INDUCED INHIBITION AND FACILITATION OF ACETYLCHOLINE RELEASE IN BRAIN SLICES
Authors: BEANI L. , BIANCHI C. , SINISCALCHI A. 
Published: July 2012

The effect of morphine, methionine‐enkephalin (Met‐enkephalin) and d‐Ala2‐d‐Leu5‐enkephalin (DADLE) were tested on the spontaneous and electrically‐evoked release of acetylcholine (ACh) from superfused slices of guinea‐pig thalamus, caudate nucleus and cerebral cortex.
At no concentration did morphine, Met‐enkephalin or DADLE modify the outflow of ACh at rest but Met‐enkephalin in the presence of naloxone, reduced the resting ACh release.
Morphine, at a low dose (3 μm) had no effect in slices of cerebral cortex, but it enhanced the evoked release of ACh in thalamic and caudate, slices. At higher doses of morphine (10–30 μm), the ACh release evoked by electrical pulses was significantly inhibited in every area.
Met‐enkephalin behaved like morphine in thalamic slices, whereas DADLE, a specific < 5 agonist, produced a slight inhibition of ACh outflow only at 10 μm.
Naloxone antagonized the inhibitory effect of morphine in the cerebral cortex and caudate nucleus slices. Naloxone and also spiroperidol blocked the releasing effect of morphine in caudate slices. In contrast naloxone did not affect the increase of ACh release caused by morphine and Met‐enkephalin in thalamic slices. The inhibitory effect of both opioids at high doses was reversed by naloxone so that they then enhanced ACh release.
A two fold increase of calcium concentration in the Krebs solution prevented the inhibitory effects of morphine 10 μm.
It is suggested that two receptors are present in thalamic slices, one of which inhibits and the other facilitates ACh release.
REVERSIBLE EFFECTS OF TETANUS TOXIN ON STRIATAL‐EVOKED RESPONSES AND [3H]‐γ‐AMINOBUTYRIC ACID RELEASE IN THE RAT SUBSTANTIA NIGRA
Authors: COLLINGRIDGE GRAHAM L. , DAVIES JOHN 
Published: July 2012

The effects of sublethal doses of tetanus toxin on γ‐aminobutyric acid (GABA)‐mediated synaptic transmission and [3H]‐GABA release were studied in the rat substantia nigra.
Intranigral injections of tetanus toxin at 1–5 times the mouse LD50 dose produced ipsiversive circling behaviour which was maximal after 1 week and lasted 2–3 weeks. Rats then displayed normal behaviour suggesting that the effects of the toxin were fully reversible.
In the treated nigra of circling rats there was a reduction in the striatal‐evoked inhibition of compacta and reticulata neurones, but no change in their spontaneous firing rates. Some forms of striatal‐evoked excitation were also reduced. Once rats had recovered from circling no alterations in the synaptic responses were detected.
In circling rats there were no differences in the sensitivities of neurones in the treated and untreated nigra to GABA or to other inhibitory neurotransmitters.
The Ca2+‐dependent, K+‐evoked release of [3H]‐GAB A from slices prepared from the treated nigra of circling rats was less than that from the untreated nigra of circling rats. No differences in nigral [3H]‐GABA release were observed once rats had recovered from the circling behaviour.
The results demonstrate that doses of tetanus toxin which produce reversible behavioural effects can interfere reversibly with GABA‐mediated synaptic transmission by a presynaptic mechanism which probably involves a reduction in transmitter release.
DRUGS THAT INCREASE γ‐AMINOBUTYRIC ACID TRANSMISSION PROTECT AGAINST THE HIGH PRESSURE NEUROLOGICAL SYNDROME
Authors: BICHARD A.R. , LITTLE H.J. 
Published: July 2012

The effects on the high pressure neurological syndrome (HPNS) of drugs which facilitate γ‐aminobutyric acid (GABA) transmission were investigated. Threshold pressures for the onset of the behavioural signs of the HPNS in mice — tremors and convulsions were established.
Flurazepam hydrochloride 20 and 10 mg/kg and sodium valproate 800 and 400 mg/kg substantially raised the threshold pressures for both tremor and convulsions.
Amino‐oxyacetic acid 35 and 25 mg/kg and diaminobutyric acid 600 mg/kg also significantly increased the thresholds. Muscimol 1 mg/kg (and 150 ngi.c.v.) was ineffective at non‐toxic doses.
These effects paralleled the drugs' ability to raise the convulsion threshold to intravenous infusion of bicuculline in mice.
These results demonstrate that drugs with actions more selective than those of the general anaesthetics are effective against the HPNS. It is also possible that there is a GABAergic component to the effects of general anaesthetics on the HPNS.
EFFECT OF DIPYRIDAMOLE ON THE FORMATION OF 6‐OXO‐PROSTAGLANDIN F1α BY THE RAT ISOLATED AORTA AND RAM SEMINAL VESICLE MICROSOMES
Authors: BULT HIDDE , HERMAN ARNOLD G. , VAN DE VELDE VERA J.S. 
Published: July 2012

Dipyridamole (1 and 10 μm) enhanced the production of 6‐oxo‐prostaglandin F1α by rat aortic tissue.
Dipyridamole (5 to 40 μm) did not influence the PGI2‐synthetase activity in ram seminal vesicle microsomes whereas, in concentrations ranging from 100 to 200 μM, it reduced the metabolism of exogenously added arachidonic acid. The latter effect may be due to an inhibition of the cyclo‐oxygenase.
DETECTION BY FLUORESCENCE OF PEROXIDES AND CARBONYLS IN SAMPLES OF ARACHIDONIC ACID
Authors: GUTTERIDGE JOHN M.C. , KERRY PHILIP J. 
Published: July 2012

Products of lipid peroxidation were compared in two different grades of commercially‐obtained arachidonic acid.
The less pure 90% sample was yellow in colour, had low reactivity with 2‐thiobarbituric acid and diene conjugation but high u.v. fluorescence, whereas the 99% pure sample, which was clear in colour, showed a reverse pattern of oxidation products.
The significance of these findings is discussed.