bluuebunny/crossref_metadata_2025_split huggingface dataset:
CV 6209 IS A NON‐COMPETITIVE ANTAGONIST OF PLATELET‐ACTIVATING FACTOR RECEPTORS ON GUINEA‐PIG RESIDENT PERITONEAL MACROPHAGES
Authors: Stewart Alastair G. 
Published: June 2007

SUMMARY1. The characteristics of antagonism of platelet‐activating factor (Paf) receptors by the phospholipid Paf analogue, CV 6209, were studied in rabbit platelets and polymorphonuclear leucocytes (PMN) and in guinea‐pig macrophages.2. Paf‐induced aggregation of PMN or platelets was antagonized in a competitive and specific manner by CV 6209 with no detectable difference between the pA2 values (approximately 9.5).3. The specificity of CV 6209 (1–100 nmol/L) for Paf receptors in platelets and PMN was indicated by a lack of effect on A23187 (10 μmol/L) or fMLP (1 μmol/L) induced aggregation, respectively.4. CV 6209 (1–100 nmol/L) was also a potent antagonist of Paf‐induced prostacyclin (PGI2) generation by guinea‐pig peritoneal macrophages. However, CV 6209 caused significant depression of the maximum response to Paf and a non‐parallel shift in the concentration‐response curve indicating a non‐competitive type antagonism.5. PGI2 generation induced by the ionophore A23187 was unaffected by CV 6209 (up to 100 nmol/L) whereas basal PGI2 production by macrophages was reduced by lower concentrations (10–100 nmol/L). These observations are not consistent with a direct effect of CV 6209 on the enzymes involved in PGI2 synthesis but do suggest that endogenous Paf regulates basal PGI2 generation.6. The non‐competitive antagonism of guinea‐pig macrophage Paf receptors gives further support to the contention that these receptors are distinct from those mediating aggregation of platelets and PMN,
MEASUREMENT OF NET SODIUM INTAKE BY THE OVINE FETUS WITH OESOPHAGEAL LIGATION
Authors: Lumbers Eugenie R. , Smith Francine G. 
Published: June 2007

SUMMARY1. If the fetal sheep is in sodium balance, then the net intake of sodium is equal to the sum of the losses of sodium in fetal urine and lung liquid plus the rate of deposition of sodium with growth.2. In seven fetal sheep with oesophageal ligation net sodium intake was 23.1 ± 2.8 (s.e.m.) μmol/min per kg; 11.8 ± 1,4 μmol/min per kg was excreted by the lungs and 8.7 ± 2.3 μmol/min per kg was excreted by the kidneys. The excretion of sodium by the lungs accounted for 52.8 ± 4.8% of the total amount of sodium; the excretion of sodium by the kidneys accounted for 34.9 ± 5.4% and the calculated variable, that is, sodium deposited due to growth was 12.3 ± 1.4%.3. All but one fetus excreted more sodium from the lungs than from the kidneys. There was no relationship between the clearance of sodium by the lungs and net sodium intake but there was a direct relationship between renal sodium clearance and net sodium intake (r=0.92, P < 0.005). This suggests that fetal urinary sodium excretion is dependent upon net sodium intake by the fetus. This animal model shows that normally there must be sodium fluxes from allantoic and/or amniotic cavities to either the fetus or the ewe.
EFFECTS OF AUTONOMIC BLOCKADE ON THE HYPERTENSIVE RESPONSE OF THE FETUS TO HYPEROSMOLALITY
Authors: Kingsford Nicola M. , Lumbers Eugenie R. 
Published: June 2007

SUMMARY1. Infusions of hyperosmotic mannitol to the ewe caused a rise in fetal arterial pressure in 17 chronically catheterized fetal sheep aged 120–140 days. The fetal heart slowed in 13 out of 17 of these fetuses. The rise in pressure occurred before there was any rise in fetal urinary osmolality.2. In seven fetal sheep combined α‐ and β‐adrenoceptor and muscarinic blockade delayed the onset of the rise in blood pressure and no bradycardia was observed. It is concluded that the hypertension was due in part to increased activity of the sympatho‐adrenal system, and that any reflex bradycardia that occurred was mediated by the vagus.3. In three other fetal sheep aged 125–131 days, the cardiovascular responses elicited by infusion of hyperosmotic mannitol to the ewe were not blocked by a specific vasopressin antagonist. Thus vasopressin could not be responsible for either the initial rise in pressure nor the delayed hypertensive response that was not blocked by α‐ and β‐adrenoceptor blockade.4. Fetal blood volume was maintained even though the changes in plasma osmolality and electrolytes were indicative of a fall in blood volume. Thus changes that threaten maintenance of fetal blood volume seem to induce increased solute and water transport across the placenta or from the extracorporeal fluid compartments.
ROLE OF GABAERGIC SYSTEM IN PROLACTIN ANALGESIA
Authors: Ramaswamy S. , Suthakaran C. , Bapna J. S. 
Published: June 2007

SUMMARY1. The role of the GABAergic system in the analgesic action of prolactin was investigated using a pharmacological approach.2. THIP, a GABAmimetic, per se produced an analgesic effect and potentiated the analgesic effect of prolactin and morphine.3. Bicuculline, in subconvulsive doses, per se did not alter the number of writhings, while it attenuated the analgesic effect of prolactin.4. These results indicate a positive role for the GABAergic system in prolactin induced analgesia.5. Since THIP resembles morphine and because prolactin possesses several other morphine‐like functions, it is possible that the role played by GABA may be an opioid‐related one.
MICROPUNCTURE COMPARISON OF NEPHRON FUNCTION DURING ACUTE AND CHRONIC ADH EXCESS IN THE RAT
Authors: Field Michael J. , Seow Francis , Lawrence James R. 
Published: June 2007

SUMMARY1. The aim of this study was to compare the effect of acute versus chronic ADH administration on the handling of sodium, potassium and water by the nephron. Simultaneous clearance and free‐flow micropuncture experiments were performed on rats, infused with hypotonic Ringer solution, following either 1–3 h ('acute') or 10–12 days ('chronic') of continuous treatment with arginine vasopressin, 50 mU/h. A third group of animals receiving no exogenous ADH acted as controls.2. Chronic ADH treatment led to more profound concentration of the urine and antidiuresis than acute treatment, due to enhanced extraction of water in the renal medulla.3. Fractional sodium excretion during this protocol was increased after ‘acute’ but not ‘chronic’ ADH treatment. The acute natriuretic response was brought about principally along the length of the proximal tubule, probably due to volume expansion and increased arterial blood pressure.4. Fractional excretion of potassium was also increased by ‘acute’ ADH, but this response was due to stimulation of potassium secretion in the late distal tubule.5. It is concluded that acute and chronic exposure to ADH have different effects on nephron function, as a result of both direct and indirect actions.
INHIBITORY EFFECT OF OUABAIN AND ACETAZOLAMIDE ON SECRETIN‐STIMULATED PANCREATIC EXOCRINE SECRETION IN ANAESTHETIZED DOG
Authors: Iwatsuki K. , Horiuchi A. , Yonekura Y. , Chiba S. 
Published: June 2007

SUMMARY1. The effects of ouabain and acetazolamide on the secretion of pancreatic juice stimulated by secretin in anaesthetized dogs were investigated.2. Intra‐arterial injection of ouabain (1–10 μg) and acetazolamide (1–10 mg) caused dose‐dependent decreases in the volume of pancreatic juice. When both drugs were added together, the inhibitory effects were significantly higher than for each drug alone.3. The bicarbonate concentration in the pancreatic juice was decreased and the chloride concentration was increased by ouabain and acetazolamide, but sodium and protein concentrations were not modified.4. The results suggest that the Na+K+‐ATPase and carbonic anhydrase activities play important roles in water and electrolyte secretion, and that ouabain and acetazolamide inhibit secretin‐stimulated pancreatic secretion by acting on different systems in the exocrine cells in dogs.
CARDIOVASCULAR ACTIONS OF HUMAN ENDOTHELIN IN CONSCIOUS SHEEP
Authors: Scoggins Bruce A. , Spence Campbell D. , Parkes David G. , McDonald Michele , Wade John D. , Coghlan John P. 
Published: June 2007

SUMMARY1. Synthetic human endothelin was injected intravenously over the range 1.5–50 μg to examine its cardiovascular actions in conscious sheep.2. Mean arterial pressure increased by 9–21 mmHg within 30–120s over the range 5–50 μg endothelin. The increase in blood pressure was associated with increased calculated total peripheral resistance and a fall in cardiac output and heart rate. Stroke volume was increased.3. Injection of endothelin into ganglion blocked sheep produced vasoconstriction and an increased blood pressure response associated with an attenuation of the effects on cardiac output, heart rate and stroke volume.4. This study suggests that endothelin produces potent arterial vasoconstriction and reflex mediated effects on the heart in conscious sheep.
POTENTIATION OF FENFLURAMINE‐INDUCED ACTH RELEASE IN MAN BY NALOXONE
Authors: Jackson Richard V. , Grice Jeffrey E. , Jackson A. Jane , Vella Rodney D. 
Published: June 2007

SUMMARY1. This study set out to compare the effect of the combination of fenfluramine (Fen) and naloxone (Nal) on ACTH and cortisol release with each of these agents alone in six normal volunteers. Three protocols were used: 1.5 mg/kg bodyweight oral Fen; 125 μg/kg bodyweight i.v. Nal; oral Fen plus i.v. Nal 135 min later. Plasma ACTH and cortisol were measured at intervals of 285 min over each test.2. The mean peak levels and mean peak changes from basal in plasma ACTH and cortisol were significantly greater in the combination test (Fen/Nal) than in either the Fen alone or the Nal alone tests. Fen and Nal given together cause a synergistic release of ACTH and cortisol as determined by the areas under the ACTH‐time and cortisol‐time curves for Fen/Nal compared to the sums of Fen alone plus Nal alone curves for ACTH and cortisol.3. We conclude that Fen and Nal acting synergistically work through different and potentiating mechanisms at the hypothalamic, central nervous system and/or pituitary levels to cause ACTH release.
LEVELS OF ATRIAL NATRIURETIC PEPTIDE ARE NOT ALWAYS CONSISTENT WITH ATRIAL PRESSURE: IS THERE ALTERNATIVE REGULATION AS EVIDENCED IN GORDON'S AND BARTTER'S SYNDROMES?
Authors: Klemm Shelley A. , Gordon Richard D. , Tunny Terry J. , Hawkins Peter G. , Finn Wendy L. , Hamlet Stephen M. , Kewal Narendra K. , Purton Karen J. 
Published: June 2007

SUMMARY1. In Bartter's syndrome, atrial pressures were low, consistent with volume contraction, while atrial natriuretic peptide (ANP) levels were unexpectedly elevated. Infusion of normal saline increased both right atrial pressure (RAP) and ANP levels, while administration of prostaglandin inhibitors raised RAP, probably due to volume expansion, but ANP levels fell paradoxically.2. In Gordon's syndrome, atrial pressures were unexpectedly low or normal despite volume expansion, while ANP levels were normal. Pressor infusions of angiotensin II either raised right and left atrial pressures (LAP) without increasing ANP, or increased ANP without increasing atrial pressures.3. In these two syndromes, atrial pressures and ANP levels were poorly correlated, leading to the proposal that other regulators of ANP may be important.
PHAEOCHROMOCYTOMAS SECRETING ADRENALINE BUT NOT NORADRENALINE DO NOT CAUSE HYPERTENSION AND REQUIRE PRECISE ADRENALINE MEASUREMENT FOR DIAGNOSIS
Authors: Bachmann Anthony W. , Hawkins Peter G. , Gordon Richard D. 
Published: June 2007

SUMMARY1. Urinary noradrenaline (NA) and adrenaline (ADR) determinations are a more sensitive index than plasma measurements for the diagnosis of phaeochromocytoma (phaeo).2. Even though urinary NA excretion serve as a sufficient single diagnostic test for the majority of phaeos, it is necessary to measure urinary ADR excretion if ADR‐only secreting phaeos are not to be missed, particularly in patients with multiple endocrine neoplasia (MEN) syndrome.3. The clonidine suppression test confirmed all tumour diagnoses, and in this series was not responsible for any false negative or false positive results.
EFFECT OF ENALAPRIL ON HANDLING OF A SODIUM CHLORIDE LOAD BY GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: Ledingham Janet M. , Simpson F. O. 
Published: June 2007

SUMMARY1. Enalapril was given in the drinking water (300 mg/L) for 4.5 days to normotensive (N) and genetically hypertensive (GH) rats on zero sodium intake. An intraperitoneal NaCl load was given 12 h after enalapril was started.2. Enalapril did not increase the maximum rate of sodium excretion, but caused the rats to excrete more than the load in the first 24 h and then to have a slow fall in body sodium while on a sodium‐free diet.3. In terms of the Strauss et al. (1958) concept of body sodium, enalapril appears to lower the basal level. However, in addition it causes a slow leak of sodium which becomes apparent when sodium intake is very low.
EFFECT OF Na+ PUMP SUPPRESSION ON REACTIVITY OF RAT TRACHEALIS TO COOLING
Authors: Chen W. Y. 
Published: June 2007

SUMMARY1. This study tests the hypothesis that suppression of Na+ pump would increase the rate of tension development and the magnitude of contraction induced by cooling in airway smooth muscle.2. Rat tracheal preparations were incubated in ouabain for 8 h and tested hourly for their response. In a representative specimen the rate of tension development increased from the control value of 0.7 mg/s to 5.5 mg/s after 7 h of incubation in ouabain concentration of 4 × 10−4 mol/L; likewise, the magnitude of contraction increased from the control value of 80 mg to 550 mg.3. Using ouabain concentrations between 9 × 10−5mol/Land6 × 10−3mol/L, the rate of tension development and the magnitude of contraction first increased in a dose‐dependent manner up to 8 × 10−4 mol/L, then declined with higher doses but the responses were still greater than the control values at all concentrations.4. After 3 h incubation in ouabain at 8 × 10−4 mol/L, the mean rate of tension development and the mean magnitude of contraction increased to 647% and 578% of the control value, respectively.5. These results indicate that depression of Na+ pump results in hypersensitivity and hyper‐reactivity of the airway smooth muscle to cooling.
DOES PERIPHERAL COLLATERALIZATION ALSO CAUSE COLLATERALIZATION IN THE CANINE HEART?
Authors: Hengy Ben , Watanabe Noriyasu , Williams Arthur G. , Downey H. Fred 
Published: June 2007

SUMMARY1. Experiments were conducted in chronically prepared dogs to determine if gradual obstruction of the proximal femoral arteries would also cause collateralization in the coronary circulation.2. Peripheral coronary pressure was measured before and after peripheral collateralization as an index of coronary collateral function. Coronary collateral blood flow was measured with radioactive microspheres after peripheral collateralization.3. Peripheral coronary pressure was not significantly altered by peripheral collateralization. Coronary collateral blood flow measured after peripheral collateralization was similar to that reported in non‐collateralized hearts.4. Results indicated that the mechanism(s) reponsible for peripheral collateralization do not act systemically, at least not on the coronary circulation.
RENAL EFFECTS OF ATRIAL NATRIURETIC FACTOR (99–126) IN WATER‐DEPRIVED SHEEP
Authors: Yates N. A. , Coghlan J. P. , Scoggins B. A. , McDougall J. G. 
Published: June 2007

SUMMARY1. The renal response to renal arterial infusion of synthetic human atrial natriuretic factor (ANF) (99–126) at 50 μg/h was examined in conscious sheep dehydrated by 48 h water deprivation and was compared with the response of normally hydrated animals.2. Renal arterial infusion of ANF produced increases in the excretion of Na, K, Ca and urine in both dehydrated and normally hydrated animals, although the effect was significantly blunted in dehydrated animals compared with normally hydrated animals.3. The attenuation of renal effects of ANF in dehydrated animals is probably due to the negative sodium and/or fluid balance of the dehydrated animals.
EFFECTS OF RESERPINE PRETREATMENT ON NEUROEFFECTOR TRANSMISSION IN THE VAS DEFERENS
Authors: Cunnanc T. C. , Manchanda R. 
Published: June 2007

SUMMARY1. The effects of reserpine pretreatment on neurotransmission in the guinea‐pig vas deferens have been re‐examined with a view to study the role of noradrenaline (NA) in mediating postjunctional electrical responses and, in particular, excitatory junction potentials (EJP).2. Reserpine (5 mg/kg, i.p.) caused almost total depletion (below detection levels) of the NA content of the vas deferens. However, spontaneous and evoked excitatory junction potentials (SEJP, EJP) and currents (SEJC, EJC) could still be recorded in NA‐depleted tissues. The amplitude distribution of SEJC in control and reserpinized tissues was similar.3. Facilitation of EJP and EJC was markedly slowed in reserpinized tissues, EJP taking 50–60 pulses to facilitate fully. However the amplitudes of fully facilitated EJP were comparable to EJP recorded in control tissues.4. EJPs in reserpinized vasa deferentia were unaffected by the NA synthesis inhibitor, α‐methyl tyrosine, but were abolished in the presence of the stable ATP analogue α,β‐methylene ATP which desensitizes postjunctional P2‐purinoceptors.5. Local application of ATP, but not NA, mimicked the EJP. These results indicate that EJP are mediated by a non‐noradrenergic neurotransmitter, possibly ATP.
DOES SUPPRESSION OF RESPONSIVENESS TO β‐ADRENOCEPTOR ACTIVATION EXPLAIN THE ENHANCEMENT OF VASOCONSTRICTOR RESPONSES BY α2‐ADRENOCEPTOR AGONISTS?
Authors: Rand M. J. , Xiao X.‐H. , Rajanayagam S. , Story D. F. 
Published: June 2007

SUMMARY1. The α2‐adrenoceptor agonist TL99, in concentrations that had no other observable effect, enhanced constrictor responses to phenylephrine in perfused segments of the rat tail artery.2. Vasoconstrictor responses to phenylephrine were also enhanced by propranolol (0.3 μmol/L).3. Vasoconstrictor responses to phenylephrine in the presence of propranolol were further enhanced by TL99 (10 nmol/L).4. The enhancement of vasoconstrictor responses by α2‐adrenoceptor agonists is not due to the removal of a counteracting vasodilator component produced by activation of p‐adrenoceptors.
EFFECT OF HAEM ON CYTOCHROME P‐450 SYNTHESIS
Authors: May Brian K. , Hansen Antony J. 
Published: June 2007

SUMMARY1. The expression of the phenobarbital‐inducible cytochrome P‐450 mRNA species (P‐450 IIB1 and IIB2) were investigated in different tissues of rats following treatment with 2‐allyl‐2‐isopropylacetamide.2. The mRNAs were detected as a single 2.1 kb mRNA species by Northern blot analysis. These mRNAs were readily detected in liver, lung and kidney but were not detected in testis, brain or erythroid tissue.3. When rats were administered 2‐allyl‐2‐isopropylacetamide, cytochrome P‐450 levels were elevated specifically in the liver and kidney but remained undetectable in testis, brain and erythroid spleen. Thus these cytochrome P‐450 mRNAs are expressed and induced by drug in a tissue‐specific fashion. Levels of mRNA for 5‐aminolaevu‐ linate synthase, the rate controlling enzyme of haem biosynthesis, were also induced by drug in a similar tissue‐specific fashion.4. The proposal that haem is required for the transcription of cytochrome P‐450 IIB1/IIB2 and other cytochrome P‐450 genes was investigated in rat liver using succinylacetone, a specific inhibitor of the haem biosynthetic pathway.5. While 2‐allyl‐2‐isopropylacetamide induced levels of cytochrome P‐450 IIB1/IIB2 mRNAs, succinylacetone administration did not affect this induction. However, succinylacetone substantially elevated both basal and drug‐induced levels of mRNA for 5‐aminolaevulinate synthase.6. Since 5‐aminolaevulinate synthase mRNA synthesis is inhibited by the end‐product haem, the results show that lowered haem levels do not affect cytochrome P‐450 gene transcription. The work does not provide evidence for the suggestion that haem is required for cytochrome P‐450 gene transcription.
CHARACTERIZATION AND REGULATION OF RAT LIVER UDP GLUCURONOSYLTRANSFERASES
Authors: Mackenzie P. I. , Chowdhury N. Roy , Chowdhury J. Roy 
Published: June 2007

SUMMARY1. The use of DNA recombinant techniques to study UDP glucuronosyltrans‐ferases is reviewed.2. The cloning and sequencing of the cDNAs to five forms of UDP glucuronosyl‐transferase demonstrated that these proteins are encoded by a superfamily of genes.3. The substrate specificities of four isozymes have been analysed by expression of their corresponding cDNAs in cell culture.4. Analysis of liver mRNA levels using radiolabelled DNA probes demonstrated that one isozyme, UDPGTr‐2, is elevated by phenobarbital whereas a second isozyme, 4‐nitrophenol GT is elevated by 3‐methylcholanthrene. The levels of other isozymes are unaffected by these two prototypic inducers of drug metabolizing enzymes.5. The level of 4‐nitrophenol GT mRNA is elevated 10–15‐fold in hyperplastic nodules in livers of rats treated with 2‐acetylaminofluorene. Similar increases were not observed for mRNAs encoding other forms of UDP glucuronosyltransferase.
DOPAMINE RECEPTORS: CLASSIFICATION, PROPERTIES AND DRUG DEVELOPMENT
Authors: Beart Philip M. 
Published: June 2007

SUMMARY1. The pharmacology, biochemistry and structure‐activity relationships pertinent to the Dl and D2 subtypes of dopamine receptors are reviewed.2. Recent advances in receptor purification and our understanding of the secondary messenger systems involved are presented.3. Dl and D2 receptors of central nervous, endocrine and peripheral systems are identical.
THE CLASSIFICATION OF 5‐HYDROXYTRYPTAMINE RECEPTORS
Authors: Mylecharane Ewan J. 
Published: June 2007

SUMMARY1. The current classification of receptors for 5‐hydroxytryptamine (5‐HT) is based on functional studies, and encompasses three main receptor types.2. 5‐HT1‐like receptors mediate inhibition of release of various neurotransmitters from central and peripheral sites, smooth muscle contraction and relaxation (and release of endothelium‐derived relaxing factor), tachycardia, a variety of behavioural actions (for example, forepaw treading, hypothermia, hyperphagia, drug discriminative stimulus properties, nociceptive pathway modulation, and anxiolytic, anti‐aggressive and prosexual effects), and central neuronal excitatory and inhibitory activity. Selective antagonists for this receptor are not yet available, but the 5‐HT2 receptor antagonists methysergide and methiothepin have appreciable affinity for 5‐HT1‐like receptors, and 5‐carboxamidotryptamine is a selective agonist.3. 5‐HT2 receptors mediate smooth muscle contraction, platelet aggregation, increased capillary permeability, some behavioural syndromes (for example, head twitch and wet‐dog shakes) and drug discriminative stimulus properties, central neuroexcitatory effects, and some neuroendocrine functions. Ketanserin and cypro‐heptadine are selective antagonists.4. 5‐HT3 receptors mediate peripheral afferent and efferent neuroexcitatory actions, anxiogenic effects, and modulation of cytotoxic drug‐induced emesis, gastric emptying, and dopamine‐related mesolimbic hyperactivity. Selective antagonists include cocaine, MDL 72222 and ICS 205–930; 2‐methyl‐5‐HT is a selective agonist.