bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRE‐AND POSTJUNCTIONAL EFFECTS OF NEUROPEPTIDE Y ON THE RABBIT ISOLATED EAR ARTERY
Authors: Wong‐Dusting H. K. , Rand M. J. 
Published: June 2007

b1. In the isolated perfused and superfused rabbit ear artery, neuropeptide Y (NPY, 0.3–100 nmol/l) had no direct vasoconstrictor action, but produced a concentration‐dependent and reversible enhancement of vasoconstrictor responses to both sympathetic nerve stimulation and exogenous noradrenaline.2. In arteries in which the noradrenergic transmitter stores had been radiolabelled with [3H]‐noradrenaline, 100 nmol/l NPY inhibited the stimulation‐induced (1 Hz for 30 s) release of radioactivity, but the lower concentrations tested (10 and 30 nmol/l) had no effect. NPY (10, 30 and 100 nmol/l) had no effect on the resting release of radioactivity.3. Thus, NPY in low concentrations enhances vasoconstrictor responses in the rabbit ear artery by a postjunctional action; prejunctionally, NPY inhibits stimulation‐induced transmitter release when it is present in high concentrations.
EFFECTS OF TUBOCURARINE ON END‐PLATE CURRENT RUNDOWN AND QUANTAL CONTENT DURING RAPID NERVE STIMULATION IN THE SNAKE
Authors: Harborne A. J. , Bowman W. C. , Marshall I. G. 
Published: June 2007

SUMMARY1. The effects of tubocurarine, pancuronium, vecuronium and trimethyl‐tubocurarine were examined on the amplitudes of end‐plate currents (EPC) produced by repetitive nerve stimulation in cut voltage‐clamped fibres of the costocutaneous muscle of the garter snake. The effects of tubocurarine were further studied on the amplitudes of miniature end‐plate currents (MEPC) recorded immediately before the trains of nerve stimulation, thus allowing estimates to be made of EPC quantal content.2. All four compounds increased the decline of EPC amplitude with successive impulses (rundown), compared with that observed in control end‐plates. There was little effect on the decay time constants of EPC and the effects on rundown were not dependent on membrane potential, indicating that end‐plate ion channel blockade was not a major effect in producing rundown.3. In the presence of tubocurarine the quantal content of the EPC in the plateau phase of the trains was reduced when compared with control, indicating a reduction of transmitter mobilization. However tubocurarine had no significant effect on the quantal content of the first EPC of the trains, indicating that the decreased mobilization is not due to an initial effect on transmitter release.4. It is suggested that the prejunctional effect of tubocurarine which results in increased EPC train rundown is primarily on transmitter mobilization. It is also suggested that the actions of tubocurarine and the other neuromuscular blockers tested are mediated through a prejunctional nicotinic receptor which may act as a positive feedback mechanism modulating transmitter mobilization.
EFFECTS OF ORPANOXIN ON ARACHIDONIC ACID METABOLISM OF HUMAN POLYMORPHONUCLEAR LEUCOCYTES AND PLATELETS IN VITRO
Authors: Doerr Iris L. , Kaufman Jeffrey , Brooks Robert R. 
Published: June 2007

SUMMARY1. The effect of orpanoxin, a nonsteroidal anti‐inflammatory drug, on cyclooxygenase and lipoxygenase activity in human polymorphonuclear leucocytes (PMNL) and platelets was studied ex vivo to see if lipoxygenase inhibition contributed to orpanoxin's mechanism of action.2. In PMNL, orpanoxin (50, 100, and 200 μmol/l), like indomethacin (100 μmol/l), had little effect on synthesis of leukotriene B4 or 5S‐hydroxy‐6‐trans,8,11,14‐cis‐eicosatetraenoic acid. BW755c at 100 μmol/l inhibited synthesis of both.3. In PLT, orpanoxin (100 μmol/l) inhibited formation of cyclooxygenase products (thromboxanes, prostaglandins, and 12‐l‐hydroxy‐5,8,10‐heptadecatrienoic acid) and increased synthesis of the lipoxygenase product, 12S‐hydroxy‐5,8‐cis, 10‐trans,14‐cis‐eicosatetraenoic acid. Effects of indomethacin (100 μmol/l) and benoxaprofen (100 μmol/l) in platelets were qualitatively similar to those of orpanoxin.4. These results indicate that the discrepancy between the low potency of orpanoxin in inhibiting bovine seminal vesicle cyclooxygenase in vitro and its high potency as an anti‐inflammatory agent in vivo is not explained by its having an additional lipoxygenase inhibitory mechanism.
MODULATION OF ADRENAL CATECHOLAMINE RELEASE BY DA2 DOPAMINE RECEPTORS IN THE ANAESTHETIZED DOG
Authors: Foucart S. , Lacaille‐Belanger P. , Kimura T. , Nadeau R. , de Champlain J. 
Published: June 2007

SUMMARY1. The effects of DA2 agonist, quinpirole (50 μg/kg, i.v.) and a DA2 antagonist, domperidone (50 μg/kg, i.v.) on the release of adrenal catecholamines were evaluated in the anaesthetized and vagotomized dog.2. Stimulations (5 V pulses of 2 ms duration for 3 min) of the splanchnic nerve at frequencies of 1, 3 and 5 Hz were applied randomly before and after injection of the drug.3. The results show that quinpirole reduces significantly the release of adrenaline at 1 and 3 Hz but not at 5 Hz, while the release of noradrenaline is reduced at 1 Hz but not at 3 and 5 Hz. Inversely, domperidone potentiates significantly the release of both catecholamines at 3 and 5 Hz, but not at 1 Hz.4. There was no change in basal release of adrenal catecholamines, adrenal blood flow or heart rate after both drug treatments.5. The mean arterial pressure was not affected by domperidone treatment but there was a significant reduction in basal mean arterial pressure after the injection of quinpirole.6. There was no change in any of these parameters during electrical stimulation.7. Therefore, these results strongly suggest that DA2 dopamine receptors are present at the level of the adrenal medulla and that their activation could mediate an inhibitory modulation on the adrenal catecholamines release within a certain range of electrical stimulation.
POTASSIUM EXCRETION IN RENAL FAILURE IN THE RAT: THE ROLE OF DISTAL TUBULE FLOW AND ALDOSTERONE
Authors: Adam William R. , Adams Beverlie A. , Ellis Andrew G. 
Published: June 2007

SUMMARY1. This study examines the contribution of an increased distal tubule flow and of aldosterone to the handling of a potassium load in conscious rats with renal failure induced by subtotal nephrectomy or by gentamicin on a control or high K+ diet.2. Glomerular filtration rate was reduced by subtotal nephrectomy to 40% and by gentamicin treatment to 60% of control. Subtotal nephrectomy induced significant hypertrophy of glomeruli and proximal and distal tubules, but gentamicin did not. Both experimental groups had a normal iothalamate space and plasma potassium after a 20 h fast.3. Two hours after an acute KCl load rats with renal failure excreted less potassium than control rats. There was also a lesser natriuretic effect of KCl in the renal failure groups.4. A high K+ diet, given for 5–7 days, increased excretion of an acute KCl load in control rats and rats with renal failure.5. (UNaV + UKV) was used as an estimate of distal tubule flow. Potassium excretion, related to distal tubule flow, was similar in the renal failure and control rats when on the same diet. This is consistent with potassium excretion being strongly, but not necessarily solely, dependent on distal flow.6. Adrenalectomy reduced, and aldosterone restored, potassium excretion in the renal failure and control groups. This suggests a role for aldosterone in excretion of an acute potassium load with this degree of renal failure.
HUMAN PLACENTAL ACETYLCHOLINE CONTENT AND RELEASE AT PARTURITION
Authors: Brennecke S. P. , Chen S. , King R. G. , Boura A. L. A. 
Published: June 2007

SUMMARY1. Measurements were made of human placental acetylcholine (ACh) content and release into maternal and fetal circulations from placenta obtained before, during and after labours of both spontaneous and induced onsets. ACh content was determined in ex vivo placental biopsies using a radio‐enzymatic assay. ACh release was determined by bioassay of the effluent from placental lobules perfused with amniotic fluid‐like Kreb's containing physostigmine (2.4 μmol/1).2. ACh content of placentae obtained after labour (spontaneous onset of labour, normal vaginal delivery) and during labour (spontaneous onset of labour, Caesarean section delivery) was significantly less than before labour (no labour onset, Caesarean section delivery).3. Mean ACh output into maternal vessels 1.5–4.0 h after commencement of perfusion of placentae obtained after labour (spontaneous onset of labour, normal vaginal delivery) was significantly less than from those obtained before labour (no labour onset, Caesarean section delivery). No differences were found in ACh output into fetal vessels of placentae obtained before, during or after labour.4. These results suggest a role for placental ACh in the events of human labour. The decrease in ACh content and maternal vascular release in placenta obtained after labour is consistent with a depletion of placental ACh during labour which may indicate ACh release at this time. The lack of any significant change in fetal vascular release of ACh in placenta obtained before, during or after labour, raises the possibility of different roles for ACh released into fetal and maternal vasculature.
CARDIOVASCULAR EFFECTS OF RILMENIDINE, A NEW α2‐ADRENOCEPTOR AGONIST, AND CLONIDINE IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Sannajust F. , Julien C. , Barrès C. , Cerutti C. , Koenig‐Bérardd̊ E. , Sassard J. 
Published: June 2007

SUMMARY1. The acute and chronic effects of rilmenidine, a partial agonist of α1‐ and α2‐adrenoceptors with antihypertensive properties, were compared to those of clonidine on blood pressure (BP), heart rate (HR) and the urinary excretion of catecholamines, which was used as an index of sympathetic activity.2. As these drugs are known to interfere centrally and peripherally with the sympathetic nervous system, long‐term arterial blood pressure recordings in freely moving unstressed adult spontaneously hypertensive rats (SHR) were used.3. Acute i.v. administrations of rilmenidine (0.3 mg/kg at 1200 h, 1.2 mg/kg at 1700 and 2200 h) and clonidine (12 μg/kg at 1200 h, 50 μg/kg at 1700 and 2200 h) induced short‐lasting increases in BP associated with a decrease in HR, which were followed by prolonged, dose‐dependent decreases in BP without bradycardia. The pressor effect was less marked and the associated bradycardia was more marked in active SHR with physiologically high sympathetic activity than in resting SHR.4. A 12‐day oral treatment with rilmenidine (6.0 mg/kg daily) or clonidine (150 μg/kg daily) induced moderate decreases in BP without change in HR. Rilmenidine but not clonidine decreased normetanephrine (NMN) excretion in active but not in resting SHR.5. Finally, during the 24 h following the cessation of the treatments, BP returned to normal, without significantly exceeding that of untreated controls. However, upswings in BP or HR were observed, more markedly and frequently after clonidine than after rilmenidine.6. In conclusion the effects of α2‐adrenoceptor agonists appear to be influenced by the pre‐existing sympathetic tone. The general agreement between these data and those observed in patients demonstrates that the use of conscious unstressed animals is of value to determine the cardiovascular effects of drugs which act on the sympathetic nervous system.
CHANGES IN MET‐ENKEPHALIN AND β‐ENDORPHIN CONTENTS IN THE HYPOTHALAMUS AND THE PITUITARY IN DIABETIC RATS: EFFECTS OF INSULIN THERAPY
Authors: Tang Fai 
Published: June 2007

SUMMARY1. Immunoreactive (IR)‐met‐enkephalin and β‐endorphin contents in the hypothalamrus and the pituitary were measured in alloxan‐diabetic rats with or without insulin treatment.2. Both IR‐met‐enkephalin and IR‐β‐endorphin in the pituitary were substantially reduced in alloxan‐diabetic rats 1 month after treatment.3. Hypothalamic IR‐β‐endorphin content was also significantly lower.4. Gel‐filtration chromatography showed that the peaks co‐eluting with met‐enkephalin precursor, met‐enkephalin and β‐endorphin were lower in the pituitaries from the diabetic rats, whereas the peaks co‐eluting with β‐endorphin precursor and β‐lipotropin were not.5. In another experiment, the IR‐β‐endorphin contents of the neuro‐intermediate lobe and hypothalamus, but not the anterior lobe were significantly lowered in diabetic rats, whereas IR‐met‐enkephalin contents were significantly reduced in both the anterior and neuro‐intermediate lobe.6. All these changes were reversed by insulin treatment.7. As a decrease in general protein synthesis could not explain the recorded changes, these results suggest a possible direct role of insulin in regulating the opioid peptide content of the hypothalamus and pituitary.
PLASMA, CARDIAC TISSUE AND BRAIN MORPHINE CONCENTRATIONS IN ACUTE AND CHRONIC MORPHINE‐TREATED RATS
Authors: Ko Wendy W‐W. , Dai Soter 
Published: June 2007

SUMMARY1. The plasma, cardiac tissues and brain morphine concentrations in rats after acute or chronic morphine treatment were measured by high‐performance liquid chromatography.2. Morphine concentrations in plasma and cardiac tissues were found to be significantly higher than those in brain after acute morphine injection. However, after chronic oral administration, morphine concentrations in plasma, cardiac tissues and brain were similar.3. Brain concentrations of morphine following chronic administration were higher than those obtained after acute administration although concentrations in plasma and cardiac tissues were lower.
IMMUNOCHEMICAL AND CATALYTICAL CHARACTERIZATION OF THE HUMAN LIVER NADPH‐CYTOCHROME P450 REDUCTASE
Authors: McManus Michael E. , Huggett Anthony , Burgess Wendy , Robson Richard , Birkett Donald J. 
Published: June 2007

SUMMARY1. The NADPH‐cytochrome P450 reductases (EC 1.6.2.4) from human and rabbit liver have been purified to electrophoretic homogeneity. The human reductase had an apparent monomeric molecular weight of 77 500 and the rabbit enzyme of 76 500.2. Both flavoproteins exhibited typical flavoprotein spectra and contained equimolar quantities of FAD and FMN. The two reductases were catalytically active in reducing cytochrome c, ferricyanide and dichlorophenolindophenol, and in supporting rabbit liver cytochrome P450 Form 4 metabolism of 2‐acetylamino‐fluorene.3. An antibody raised in the goat against the human enzyme formed a precipitin line with the human reductase in a double‐diffusion assay, but did not react with the rabbit reductase. Similarly, an antibody raised in the goat against the rabbit reductase formed a precipitin line with the rabbit enzyme, but did not cross‐react with the human reductase.4. Both antibodies inhibited cytochrome c reduction by the two reductases suggesting some immunochemical recognition.5. Immunochemical cross‐reactivity was confirmed when both reductases were subjected to the more sensitive immunoblot technique using either anti‐human or anti‐rabbit reductase IgG.6. The human and rabbit reductases are essentially similar in amino acid composition, except that the former has larger amounts of serine and glycine.
RAT AORTIC ENDOTHELIUM ANTAGONIZES NITROPRUSSIDE‐INDUCED RELAXATION BY RELEASE OF THE PEPTIDE ENDOTHELIN
Authors: Macdonald P. S. , Kudo K. , Dubbin P. N. , Dusting G. J. 
Published: June 2007

SUMMARY1. The effects of porcine endothelin were examined in rat thoracic aortic rings.2. Endothelin was a potent contractile agonist (EC50 4.0 ± 0.6 nmol/L).3. Endothelin (1 nmol/L) did not affect contractile responses to cumulative concentrations of the thromboxane analogue, U46619.4. In the presence of U46619, but not phenylephrine, endothelin (1 nmol/L) and endothelium abrogated the vasodilator response to cumulative concentrations of sodium nitroprusside.5. The inhibitory effect of endothelin on vasodilator responses to nitroprusside in the presence of U46619 was abolished by nifedipine (0.1 μmol/L) but unaffected by indomethacin (3 μmol/L) or haemoglobin (10 μmol/L).6. These data suggest that endothelin generated by native endothelium exerts a physiological antagonism of sodium nitroprusside in the presence of thromboxane.
PARADOXICAL EFFECTS OF ENDOTHELIN ON CARDIOVASCULAR NORADRENERGIC NEUROTRANSMISSION
Authors: Wong‐Dusting H. K. , Reid J. J. , Rand M. J. 
Published: June 2007

SUMMARY1. Pre‐ and postjunctional effects of endothelin (1–10 nmol/L) have been studied in the rabbit isolated ear artery and in rat isolated atria.2. Endothelin produced concentration‐dependent increases in arterial perfusion pressure, and had positive chronotropic and inotropic effects in rat atria.3. Vasoconstrictor responses of the arteries to sympathetic nerve stimulation were reduced by 1 nmol/L endothelin and abolished by 10 nmol/L endothelin. In rat atria, the chronotropic responses to nerve stimulation were markedly reduced by 10 nmol/L endothelin.4. In rabbit ear artery, vasoconstrictor responses to noradrenaline were enhanced by 1 nmol/L endothelin, but were reduced by 10 nmol/L endothelin. In rat atria, endothelin reduced the chronotropic response to isoprenaline.5. Endothelin (10 nmol/L) increased the stimulation‐induced release of radioactivity in arteries and atria labelled with [3H]‐noradrenaline by 91% and 23%, respectively.6. The p‐ and postjunctional effects of endothelin persisted in both arterial and atrial preparations for at least 30 min after its removal.
BIOCHEMICAL AND HORMONAL CHANGES DURING A 1000 km ULTRAMARATHON
Authors: Pestell Richard G. , Hurley David M. , Vandongen Robert 
Published: June 2007

SUMMARY1. To examine individual hormonal responses to extreme physical stress, blood samples were taken from eight highly trained athletes 1 day before and within 15 min of finishing the 1986 1000 km Sydney to Melbourne Ultramarathon foot race.2. The baseline hormonal state of these highly trained athletes was quite different from normal. Resting serum conjugated catecholamines — epinephrine (E), nor‐epinephrine (NE), dopamine (D), free E and free D — were significantly elevated above the normal mean (P < 0.01). ACTH levels were significantly elevated above the normal range. Immunoreactive β‐endorphin (IR‐βEP), growth hormone (GH), prolactin (PRL), testosterone, cortisol and cortisol‐binding globulin (CBG) were within the normal range.3. The effect of the race on serum catecholamine levels was to elevate further free and conjugated NE (P < 0.01). Other catecholamines, free and conjugated, remained significantly elevated above the normal mean (P < 0.01). Adrenocorticotrophic hormone (ACTH) remained elevated, and IR‐βEP within the normal range, without significant change. A significant increase in GH (P < 0.05), PRL (P < 0.01), and cortisol (P < 0.01) was seen, with no change in CBG.4. As a model of chronic physical stress, the ultramarathon runner demonstrates a significantly altered baseline hormonal state as reflected in the primary mediators of the stress response, the catecholamines and the hypothalamic‐pituitary‐adrenal axis. Their response to severe exercise is distinct from that of untrained individuals in whom conjugated catecholamines decrease and ACTH increase. This may represent hormonal adaptation to prolonged stress.
HYPOTHERMIA ENHANCES THE EFFECTS OF MORPHINE ON HORMONAL AND HISTAMINE RELEASE
Authors: Alcaraz Cristina , Bansinath Mylarrao , Turndorf Herman , Puig Margarita M. 
Published: June 2007

SUMMARY1. The effects of intravenous (i.v.) morphine on adrenocorticotrophic hormone (ACTH), β‐endorphin (β‐END), total catecholamines (CA) and histamine (HIS) plasma concentrations, were determined in anaesthetized dogs at 30°C and 37°C.2. Hypothermia initially increased CA levels by 29%, but the values returned to baseline after 2 h. Morphine (1 mg/kg, i.v.) produced a significant decrease in CA both at 37°C and 30°C (34% and 54%, respectively). Subsequent administration of naloxone (1 mg/kg, i.v.) significantly increased CA levels in both groups.3. Hypothermia per se had no effect on ACTH, β‐END, and HIS concentrations. Morphine produced a significant increase in pituitary hormones and HIS, in hypo‐ thermic but not in normothermic animals. Morphine concentrations were significantly higher at 30°C during the first 45 min.4. The results suggest that the effects of morphine on hormonal and histamine release observed at 30°C are concentration‐dependent and related to changes in morphine pharmacokinetics.
PROCONVULSANT EFFECT OF PAPAVERINE ON THEOPHYLLINE‐INDUCED SEIZURES IN RATS
Authors: Ramzan Iqbal 
Published: June 2007

SUMMARY1. The effects of papaverine, an adenosine uptake inhibitor, were tested against theophylline‐induced seizures.2. Rats were infused with a constant intravenous infusion of theophylline at 10.3 mg/min immediately following intraperitoneal pretreatment with either papaverine 35 mg/kg or saline vehicle.3. Papaverine produced a potent proconvulsant effect towards theophylline seizures, reducing the onset time and cumulative dose to seizure and theophylline concentrations in arterial serum, cerebrospinal fluid and brain, respectively, at onset of maximal seizures.
ENANTIOSELECTIVE DRUG ANALYSIS: PROBLEMS AND RESOLUTIONS
Authors: Nation Roger L. 
Published: June 2007

SUMMARY1. With the increasing appreciation that the enantiomers of a chiral drug can differ pharmacokinetically and/or pharmacodynamically, there is considerable interest in methods for the resolution and quantification of enantiomers.2. Enantiomers possess identical physical and chemical properties in a symmetrical environment and, therefore, their resolution requires the introduction of an asymmetric or chiral environment allowing diastereomeric interactions. This can be achieved using a number of chromatographic techniques, of which the most developed and widely used is high‐performance liquid chromatography (HPLC).3. Resolution and quantification of enantiomers can be performed using HPLC by either converting the enantiomers to covalent diastereomers prior to chromatography or introducing a chiral environment to the chromatographic system, thereby allowing temporary diastereomeric interactions.4. Antibodies are chiral molecules which can bind the enantiomers of a chiral drug in a differential manner. This is the basis of enantioselective immunoassay, which is a promising technique for the enantioselective analysis of drugs in biological fluids.5. Each of the methods available has its limitations, advantages and potential applications in the pharmaceutical industry.
RACEMATES OR ENANTIOMERS: REGULATORY APPROACHES
Authors: Birkett D. J. 
Published: June 2007

SUMMARY1. Racemic drugs contain enantiomers which can differ substantially in pharmacological and dispositional properties. The development of chemical methods to separate and analyse drug enantiomers has led to a growing understanding of their biological properties and a regulatory dilemma as to whether only enantiomerically pure drugs should be marketed.2. Advantages of enantiomerically pure drugs include more selective pharmacological profiles leading to better therapeutic indices, less complex pharmacokinetics and interactions, and simpler interpretation of plasma concentration response relationships.3. As racemic drugs that are currently marketed and reaching marketing were developed when knowledge of drug enantiomers was less sophisticated, a flexible regulatory approach is required. At present, it is probably reasonable to require substantial information on the properties of enantiomers of racemic drugs but the balance is on the side of regulatory agencies needing to justify, provided adequate information is submitted, requirements for enantiomerically pure drugs.4. This balance will gradually change to a situation where enantiomerically pure drugs will be the standard, and a strong case will need to be put by sponsors wishing to market racemic drugs.