bluuebunny/crossref_metadata_2025_split huggingface dataset:
POTENTIATION BY NALOXONE OF PRESSOR REFLEXES
Authors: MONTASTRUC JEAN‐LOUIS , MONTASTRUC PAUL , MORALESOLIVAS FRANCISCO 
Published: July 2012

The effect of intravenous naloxone, an opiate antagonist, was studied on the pressor responses elicited by stimulation of afferent nerves (vagus and laryngeal superior nerves) in anaesthetized dogs
Although naloxone (0.1 mg/kgi.v.) alone failed to modify basic blood pressure, the pressor responses induced by stimulation of either the vagus or laryngeal nerve were potentiated by naloxone
Morphine (0.2mg/kgi.v.) suppressed these two cardiovascular responses. These depressor effects of morphine were reversed by subsequent injection of naloxone (0.1 mg/kg i.v.)
The results suggest the involvement of endogenous opiate peptides in pressor reflexes elicited by stimulation of the afferent nerves.
THE EFFECTS OF PROSTAGLANDINS E2, F2α, PROSTACYCLIN, FLURBIPROFEN AND ASPIRIN ON ARRHYTHMIAS RESULTING FROM CORONARY ARTERY LIGATION IN ANAESTHETIZED RATS
Authors: COKER SUSAN J. , PARRATT J.R. 
Published: July 2012

Various prostaglandins and inhibitors of prostaglandin synthesis were administered prior to acute coronary artery ligation in anaesthetized rats and their effects were assessed on the number and severity of the resulting early arrhythmias (ventricular ectopic activity; incidence and duration of ventricular tachycardia and of ventricular fibrillation)
Prostaglandin E2 (PGE2), PGF2α and prostacyclin all showed antiarrhythmic activity; in contrast flurbiprofen increased the incidence of ventricular fibrillation and mortality
Both the number of ventricular ectopic beats and the incidence of ventricular fibrillation were reduced by aspirin
The results suggest that the release of endogenous PGE2, PGF2α and prostacyclin could reduce early post‐infarction ventricular arrhythmias whilst the protective effect of aspirin in this model adds further support for the hypothesis that thromboxane release is involved in the genesis of these arrhythmias.
TIME COURSE OF OUABAIN UPTAKE IN ISOLATED MYOCARDIAL CELLS: DEPENDENCE ON EXTRACELLULAR POTASSIUM AND CALCIUM CONCENTRATION
Authors: MELDGAARD L. , STEINESS E. , WALDORFF S. 
Published: July 2012

Spontaneously beating myocardial cells isolated from newborn rats have been used to evaluate the time course of cellular ouabain uptake.
The rate of cellular uptake and the amount of ouabain bound at equilibrium were computed by fitting the experimental data to the conventional exponential equation for receptor binding of drugs.
At normal extracellular potassium and calcium concentrations a biexponential equation was the best fit to the experimental data, indicating two receptor sites of ouabain with different rates of uptake.
Increasing extracellular potassium or calcium concentrations decreased the amounts of ouabain bound at equilibrium. 5 High and low extracellular concentrations of potassium or calcium decreased the rate of ouabain uptake. 6 It is well known that ouabain changes ionic fluxes. Changes in the extracellular potassium and calcium concentrations also influence the amount of ouabain taken up by myocardial cells, as demonstrated in the present study.
PARALLEL MATURATION OF THE PANCREATIC SECRETORY RESPONSE TO CHOLINERGIC STIMULATION AND THE MUSCARINIC RECEPTOR POPULATION
Authors: DUMONT Y. , LAROSE L. , MORISSET J. , POIRIER G.G. 
Published: July 2012

The appearance of pancreatic muscarinic receptors during development has been measured by use of the specific ligand [3H]‐quinuclidinyl benzilate ([3H]‐QNB).
QNB binding sites are present in foetal pancreas; their maximal concentration is attained at the age of 30 days and a significant decrease is observed in one year old animals.
Affinity of [3H]‐QNB for the muscarinic receptor does not change with age.
An evaluation of the pancreatic secretory response to a cholinoceptor agonist as a function of age indicates that the development of this response parallels that of the receptor population.
It is suggested that, at all ages from 3 days after birth onwards, the maximal secretory response of the exocrine pancreas to a cholinoceptor agonist mobilizes the same proportion of the total population of QNB binding sites.
EFFECTS OF RP AND SP DIASTEREOISOMERS OF ADENOSINE 5′‐O‐(1‐THIODIPHOSPHATE) ON HUMAN PLATELETS
Authors: CUSACK N.J. , HOURANI S.M.O. 
Published: July 2012

RP and SP diastereoisomers of adenosine 5′‐O‐(1‐thiodiphosphate) ((R)‐ADP‐β‐S and (S)‐ADP‐β‐S), an adenosine 5′‐diphosphate (ADP) analogue, were tested on intact human platelets.
Each diastereoisomer induced aggregation, (S)‐ADP‐α‐S being 5 times more potent than (R)‐ADP‐α‐S but they achieved only 75% of the maximal effect of ADP.
Aggregation induced by each diastereoisomer was competitively inhibited by ATP (50 μm)
Simultaneous addition of each diastereoisomer inhibited aggregation induced by ADP but not by 11α, 9α‐epoxymethano prostaglandin H2, a stable endoperoxide analogue. Both diastereoisomers are therefore partial agonists at the ADP receptor mediating aggregation.
Unlike ADP, neither diastereoisomer inhibited prostaglandin E1 (PGE 1‐stimulated adenylate cyclase, but each competitively inhibited the effect of ADP, with (S)‐ADP‐α‐S again being 5 times more potent than (R)‐ADP‐α‐S.
These are the first reported examples of ADP analogues to induce platelet aggregation without inhibiting PGE 1‐stimulated adenylate cyclase.
SPONTANEOUS ACTIVITY IN THE TRACHEA OF DOGS TREATED WITH INDOMETHACIN: AN EXPERIMENTAL MODEL FOR ASPIRIN‐RELATED ASTHMA
Authors: ITO YUSHI , TAJIMA KIKUO 
Published: July 2012

Electrical and mechanical properties of smooth muscle cells or of neuro‐effector transmission in the smooth muscle layer of the dog trachea, were studied after treatment with indomethacin, by means of the double sucrose gap, microelectrode or tension recording methods.
After several subcutaneous injections of indomethacin (1.0 mg/kg daily), 6 out of 12 dogs were coughing and wheezing.
Smooth muscle tissues dissected from the trachea of the coughing dog showed spontaneous electrical and mechanical activities at the frequency of 8–15 per min. These spontaneous electrical and mechanical activities were completely suppressed by treatment with atropine (106 m), isoprenaline (5 × 10−7m) or prostaglandin E2 (10−9m) but not by tetrodotoxin (1.5 × 10−6m).
Direct muscle stimulation induced oscillatory potential changes followed by tension development in the trachea of the indomethacin‐treated dog.
In the indomethacin‐treated dog, mean membrane potential of the tracheal smooth muscle cells was −52.4 mV, and in the control trachea, the potential was −59.0 mV.
In the trachea from control dogs, the amplitude of test e.j.ps after conditioning e.j.ps was always smaller than the conditioning e. j.p., at any time interval between the two stimuli. In the trachea from indomethacin‐treated dogs, facilitation phenomena were observed.
In the trachea from the indomethacin‐treated dog, prostaglandin E1 (PGE1 or PGE 2 (10−10—10−9 m) markedly suppressed the amplitude of the e.j.p. but did not affect the facilitation phenomenon.
These results indicate that endogenous prostaglandins play important physiological roles in the feed‐back inhibitory mechanisms for acetylcholine release from the nerve terminals during the resting and active states.
The results are also discussed in relation to the genesis of aspirin‐induced asthma in man.
EFFECTS OF HALOTHANE ON THE INCORPORATION OF [14C]‐SERINE INTO PHOSPHOLIPID IN THE GUINEA‐PIG ILEUM
Authors: PATON W.D.M. , WING D.R. 
Published: July 2012

The effects of halothane on the incorporation of l‐[3‐14C]‐serine into phospholipid were studied in the resting, innervated longitudinal muscle preparation of the guinea‐pig ileum.
The anaesthetic, at clinical concentrations, caused a dose‐dependent, partial inhibition of incorporation. The effect was rapid and reversible, and did not show characteristics of competitive inhibition.
The incorporation was reduced by a decrease in the Ca2+ concentration of the Krebs incubation buffer. Part of the activity persisted in the absence of added Ca2+ and this was most susceptible to inhibition by halothane. Sensitivity to external Ca2+ was not influenced at the halothane concentrations studied.
Evidence in support of the 14C‐incorporation being due to l‐[3‐14C]‐serine‐phospholipid base‐exchange activity included: (a) the rapid appearance of radioactivity in phosphatidylserine; (b) the kinetics of this incorporation in relation to that in phosphatidylethanolamine; (c) its dependence on Ca2+, and (d) its insensitivity to 2,4‐dinitrophenol and its sensitivity to temperature.
It is concluded that this preparation makes it possible for a membrane‐bound lipid‐dependent activity (l‐serine‐phospholipid base‐exchange) to be studied in conditions of cellular integrity under which the normal functional effects of lipophilic drugs can be simultaneously tested.
A rapid gas‐chromatographic assay for halothane from an aqueous medium is also described.
ANOMALOUS COMPARTMENTATION OF 5‐HYDROXYTRYPTAMINE IN INTACT HUMAN PLATELETS
Authors: COSTA J.L. , KIRK K.L. , MURPHY D.L. , STARK H. 
Published: July 2012

The movement of radiolabelled 5‐hydroxytryptamine (5‐HT) between the extracellular medium, the thrombin‐releasable (vesicular) compartment, and a non‐thrombin‐releasable compartment has been investigated in washed human platelets.
Appreciable amounts of extracellular 5‐HT can accumulate in a non‐releasable compartment. Depending on the incubation conditions and the amount of 5‐HT already present inside the cell, non‐releasable 5‐HT can either remain non‐releasable or rapidly migrate into the vesicular compartment.
Measurable amounts of vesicular 5‐HT can also enter a non‐releasable compartment. However, vesicular 5‐HT which becomes non‐releasable does not appear to mix with 5‐HT becoming non‐releasable following uptake from the extracellular medium.
Extracellular 5‐HT can be added to vesicles and to the non‐releasable compartment in the presence of appreciable quantities of 5‐HT already in one or both compartments.
The vesicular and non‐releasable compartments appear to accumulate 5‐HT independently of one another. Furthermore, most vesicular accumulation of 5‐HT occurs from the extracellular medium, rather than by translocation of non‐releasable 5‐HT into the vesicular compartment.
HYPOTENSIVE AND SEDATIVE EFFECTS OF α‐ADRENOCEPTOR AGONISTS: RELATIONSHIP TO α1‐AND α2‐ADRENOCEPTOR POTENCY
Authors: CLOUGH D.P. , HATTON R. 
Published: July 2012

The purpose of this study was to investigate whether the separation between the hypotensive and sedative effects of a new series of centrally acting antihypertensive drugs was due to differences between the relative pre‐junctional (α2) and post‐junctional (α1) adrenoceptor agonist properties of the compounds.
In anaesthetized rats the intravenous doses of clonidine, ICI 101187, ICI 106270, ICI 109683 and ICI 110802 required to lower blood pressure (BP) by 20 mmHg were 1.2, 5.1, 5.5, 3.3 and 5.4 μg/kg respectively.
In a test for sedation, ICI 101187 had at least 10 times less sedative effect than clonidine, ICI 106270 and ICI 109683 had at least 30 times less sedative effect than clonidine while ICI 110802 was not active. In a locomotor activity test the intravenous dose of clonidine required to reduce activity by 50% was 15.3 μg/kg, for ICI 101187 it was 194, for ICI 106270 it was 238 and for 110802 it was 313 μg/kg.
In the pithed rat the ED50s of clonidine, ICI 101187, ICI 106270, ICI 109683 and ICI 110802 as α2‐agonists were 19.4, 9.3, 63.2, 43.0 and 78.5 μg/kg respectively. The α1‐adrenoceptor potencies were quite similar for the five drugs and varied between 3.2 μg/kg for ICI 110802 and 8.7 μ/kg for ICI 106720. Potency as α2‐adrenoceptor agonists was also assessed in the mouse vas deferens. Clonidine and ICI 101187 were similar in potency with IC50Ss of 9.3times 10−9M and 8.9 × l0−9M respectively. ICI 106270 and ICI 110802 were much weaker with IC50Ss of 4.9 × 10−8M and over 5.7 × 10_8M respectively.
Since all the compounds had similar potencies as α1‐agonists, this could not explain their different sedative effects. The weakest compounds as sedatives were also weakest as α2‐agonists, although ICI 101187 which was as potent as clonidine as an α2‐agonist was still 10 times weaker as a sedative.
Hypotensive activity appears to be more closely related to α1‐ than to α2‐potency.
Clonidine was more potent as both a sedative and a hypotensive agent than would be predicted from its activity at either the α1‐ or the α2‐adrenoceptor.
ACTIVATION OF PREJUNCTIONAL β‐ADRENOCEPTORS IN RAT ATRIA BY ADRENALINE APPLIED EXOGENOUSLY OR RELEASED AS A CO‐TRANSMITTER
Authors: MAJEWSKI H. , RAND M.J. , TUNG L.‐H. 
Published: July 2012

Adrenaline (10 nM) significantly enhanced the stimulation‐induced efflux of radioactivity from rat atria previously incubated with [3H]‐noradrenaline ([3H]‐NA). This effect was abolished by metoprolol (0.1 μm).
Adrenaline in a higher concentration (1μm) and NA (1μm) significantly reduced the stimulation‐induced efflux of radioactivity. However, in the presence of phenoxybenzamine (10μm), adrenaline (1μm) enhanced the efflux, whereas NA (1μm) had no effect.
In rat isolated atria pre‐incubated with adrenaline and then incubated with NA, both catecholamines were taken up and were released by field stimulation. When pre‐incubation was with adrenaline and incubation was with [3H]‐NA, metoprolol decreased the stimulation‐induced efflux of radioactivity. This effect did not occur if the atria were pre‐incubated with NA instead of adrenaline, suggesting that neuronally released adrenaline activates prejunctional β‐adrenoceptors.
In conscious rats, intravenously administered adrenaline (6.0 and 0.6 nmol/kg) was taken up and retained in the atria and could be released by field stimulation. The release was calcium‐dependent from these rats up to 24 h after administration.
A BEHAVIOURAL AND BIOCHEMICAL STUDY IN RATS OF 5‐HYDROXYTRYPTAMINE RECEPTOR AGONISTS AND ANTAGONISTS, WITH OBSERVATIONS ON STRUCTURE‐ACTIVITY REQUIREMENTS FOR THE AGONISTS
Authors: GREEN A.R. , HALL J.E. , REES A.R. 
Published: July 2012

The effect of the putative 5‐hydroxytryptamine (5‐HT) receptor antagonists, methysergide, methergoline, mianserin, cyproheptadine, cinanserin (all at 10 mg/kg), methiothepin (5 mg/kg) and (−)‐propranolol (20 mg/kg) on the behavioural responses to tranylcypromine (10 mg/kg) followed 30 min later by L‐tryptophan (100 mg/kg) was examined.
Methysergide, methergoline, methiothepin and (−)‐propranolol inhibited head weaving, forepaw treading and hind‐limb abduction. Methysergide and methergoline increased reactivity. In contrast, cypropheptadine, cinanserin and mianserin had no effects on the behaviour.
Similar findings were obtained when the behaviours were elicited by administration of tranylcypromine (10 mg/kg) followed by the putative 5‐HT receptor agonist, 5‐methoxy‐N, N‐dimethyltryptamine (5‐MeODMT) (2 mg/kg).
When the behaviours were elicited by the putative 5‐HT receptor agonist, quipazine (50 mg/kg), all the drugs effectively inhibited head weaving and forepaw treading.
When the dose of cypropheptadine was doubled to 20 mg/kg an inhibition of the tranylcypromine/L‐tryptophan induced behaviours was seen.
Methiothepin produced a marked inhibition of apomorphine‐induced locomotor activity whilst all the others enhanced this response, suggesting that only methiothepin inhibits the 5‐HT behaviours by dopamine antagonism and that the increased reactivity seen following tranylcypromine/L‐tryptophan after pretreatment with methysergide or methergoline might be due to enhanced dopamine function.
Pretreatment with p‐chlorophenylalanine resulted in enhanced behavioural responses to both 5‐MeODMT and quipazine.
Both methergoline and methiothepin decreased the rate of 5 ‐HT synthesis in whole brain but not spinal cord and methergoline decreased spinal cord 5‐HIAA concentration. None of the other drugs had any significant effects on the concentration of 5‐HT, 5‐HIAA or 5‐HT synthesis rate in brain or spinal cord.
Experiments with compounds structurally related to quipazine and with molecular models suggested that quipazine produces behavioural changes probably by stimulating the 5‐HT receptor in a similar way to 5‐HT but that it would bind weakly, in agreement with ligand‐receptor binding studies.
It is suggested, therefore, that cyproheptadine, cinanserin and mianserin fail to inhibit 5‐HT and 5‐MeODMT‐induced behaviours because they are weak antagonists whilst they are able to inhibit the same behaviours induced by quipazine because it is a weak agonist.
These data indicate that extreme care should be taken in accepting or rejecting 5‐HT as a mediator of behaviours or of other responses unless several antagonists or agonists have been examined.
THEOPHYLLINE DOES NOT AFFECT MORPHINE INHIBITION OF THE ISOLATED VAS DEFERENS
Authors: STONE T.W. 
Published: July 2012

Adenosine and morphine both produced an inhibition of the electrically‐evoked twitch of the isolated superfused vas deferens of the mouse.
Theophylline, 10 or 100 μm, reduced the inhibitory action of adenosine but did not change inhibition by morphine.
It is suggested that adenosine release is not a necessary prerequisite for morphine inhibition of transmitter release. It is also suggested that the involvement of adenosine may follow activation only of opiate μ‐receptors.
THE ROLE OF PRESYNAPTIC α‐ADRENOCEPTORS IN THE REGULATION OF BLOOD PRESSURE IN THE CONSCIOUS RABBIT
Authors: HAMILTON C.A. , REID J.L. , ZAMBOULIS C. 
Published: July 2012

Changes in mean arterial pressure, heart rate and plasma noradrenaline after α‐adrenoceptor blockade with several α‐adrenoceptor antagonists have been studied in the conscious rabbit in order to investigate the possible role of presynaptic α‐adrenoceptors in cardiovascular regulation.
Prazosin (0.05–2 mg/kg) and phentolamine (0.5–20 mg/kg) produced dose‐dependent falls in mean arterial pressure and rises in plasma noradrenaline. These changes were related to the degree of postsynaptic α‐adrenoceptor blockade determined by the pressor response to intravenous phenylephrine.
Similar changes in mean arterial pressure and plasma noradrenaline were observed after administration of the direct vasodilators hydralazine (1–10 mg/kg) and nitroprusside (2.5–55 μg kg−1 min−1).
After baroreceptor deafferentation by sinoaortic denervation the falls in mean arterial pressure were much greater and the rise in plasma noradrenaline was markedly attenuated.
Yohimbine (1 mg/kg) increased mean arterial pressure and plasma noradrenaline but it was not possible to exclude the possibility that central nervous effects of yohimbine underlay the increased sympathetic activity.
The magnitude of the baroreflex response to changes in pressure make it unlikely that the functional significance of the presynaptic α‐adrenoceptor can be readily determined by measurement of plasma noradrenaline in intact animals.
THE EFFECT OF γ‐HYDROXYBUTYRATE ON MOUSE STRIATAL TYRAMINE, DOPAMINE AND HOMOVANILLIC ACID
Authors: JUORIO A.V. 
Published: July 2012

The concentrations of p‐ and m‐tyramine, dopamine and homovanillic acid were measured in the mouse striatum following the subcutaneous injection of γ‐hydroxybutyrate; their control levels were 19.8, 6.3, 9600 and 1130 ng/g respectively.
The administration of 500–1000 mg/kg of γ‐hydroxybutyrate produced a reduction in p‐tyramine that lasted at least 8 h. m‐Tyramine and dopamine were significantly increased for at least 4 h. The levels of homovanillic acid were increased at 1 and 2 h after drug administration.
These experiments strongly suggest that the increases in dopamine turnover produced by γ‐hydroxybutyrate caused reciprocal changes in striatal tyramine that are similar to those produced by drugs or treatment that increase dopamine turnover and tyrosine hydroxylase activity.
DILTIAZEM‐INDUCED VASODILATATION OF SMOOTH MUSCLE CELLS OF THE CANINE BASILAR ARTERY
Authors: FUJIWARA SHIGERU , ITO YUSHI , ITOH TAKEO , KURIYAMA HIROSI , SUZUKI HIKARU 
Published: July 2012

The effects of diltiazem on smooth muscle cells of the canine basilar artery were investigated by means of microelectrode, double sucrose gap and isometric tension recording methods.
The mean membrane potential of the smooth muscle cells was −49.8 mV and they were electrically quiescent. Diltiazem (over 10−5 m) depolarized the membrane. After pretreatment with 5 and 10 mm tetraethylammonium (TEA), an outward current pulse (1 and 2 s in duration) produced a spike and this spike was abolished by application of 10−5 m diltiazem.
The spike could also be generated by the excitatory junction potential (e.j.p.) evoked by perivascular nerve stimulation (0.05 ms in pulse duration) in the presence of 5 mm TEA. Diltiazem (> 10−6 m) suppressed both the spike and the e.j.ps, the suppression being more apparent for spike generation. The amplitude of the e.j.ps was reduced by diltiazem in concentrations greater than 10−6m. The effects were dose‐dependent: when the amplitude of e.j.ps was reduced by application of diltiazem, the resulting mechanical response was also proportionally smaller.
The contractions evoked by 128 mm [K]o, 10−3m adenosine 5′‐triphosphate (ATP) or, NaCl‐free solution were abolished in Ca‐free solutions containing 2 mm EGTA, but the amplitude of caffeine‐induced contraction (10 mm) was only slightly reduced. Diltiazem, in concentrations above 3 × 10−7m suppressed the contraction evoked by excess [K]o, ATP or caffeine, but the inhibitory action of diltiazem on the K‐induced contraction was greatest.
Following pretreatment with 2.5 mm [Ca]o, a contraction was evoked by caffeine in Ca‐free solution. The amplitude of the caffeine‐induced contraction was increased by simultaneous application of 2.5 mm [Ca]o with 128 mm [K]o and to a lesser extent by simultaneous application of 2.5 mm [Ca]o with 5.9 mm [K]o. The amplitude of the caffeine‐induced contraction generated in the presence of 5.9 mm or 128 mm [K]o was suppressed to the same extent by application of diltiazem [10−5m) during preincubation in [Ca]o. This result suggests that the Ca stored in the cell is replenished by Ca‐influx from [Ca]o during the resting and active states of the membrane, and that diltiazem has no effect on the mobilization of Ca stored in the cell.
Thus, diltiazem acts on the canine basilar artery suppressing the Ca‐influx during the active condition as a Ca‐spike suppressor and the voltage‐dependent Ca‐influx induced by excess [K]o or by chemical depolarization. Diltiazem has no effect on the Ca mobilization from the store site. This agent also suppresses the amplitude of e.j.ps due to inhibition of the release of chemical transmitter from nerve terminals following the suppression of the Ca‐influx. Diltiazem appears to act as a vasodilator on the canine basilar artery.
β2‐ADRENOCEPTORS REGULATE INDUCTION OF MYOCARDIAL ORNITHINE DECARBOXYLASE IN MICE in vivo
Authors: COPELAND JACK G. , LARSON DOUGLAS F. , ROESKE WILLIAM R. , RUSSELL DIANE H. , WOMBLE J.R. 
Published: July 2012

The pharmacological characteristics of the myocardial adrenoceptor of the mouse have been examined during embryogenesis by measuring ornithine decarboxylase (ODC, EC 4.1.1.17) induction.
A four fold elevation of ODC activity was observed after isoprenaline (10 mg/kg, s.c), and enzyme activity was increased two to three fold following adrenaline (1 mg/kg, s.c.) or terbutaline given by direct injection to the foetus (10 μg/500 mg).
Pretreatment with the β‐adrenoceptor antagonist, propranolol (10 mg/kg), totally blocked the increase in ODC activity.
Elevation of myocardial ODC activity was not inhibited by metoprolol, a relatively specific β1‐adrenoceptor antagonist, at a dose of 10 mg/kg.
Since the increase in ODC activity was blocked by a β‐adrenoceptor antagonist (propranolol) and enzyme activity was stimulated by terbutaline, a β2‐agonist, we conclude that β2‐adrenoceptors are selectively coupled to the regulation of murine cardiac ODC activity following catecholamine stimulation.