bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facilitation by tachykinins of neurotransmission in guinea‐pig pulmonary parasympathetic nerves
Authors: Hall Anthony K. , Barnes Peter J. , Meldrum Lorna A. , Maclagan Jennifer 
Published: July 2012

The effect of tachykinins on cholinergic neurotransmission was studied in an innervated tracheal tube preparation isolated from guinea‐pigs anaeshetized with urethane. The tracheal tube was bathed in Krebs‐Henseleit solution containing 5 μm indomethacin.
Neurokinin A (NKA), eledoisin (El) and substance P (SP) caused concentration‐dependent increases in intraluminal pressure (ILP), with an order of potency NKA > El >> SP.
Low concentrations of tachykinins, that had little effect on ILP, caused an increase in the contractions elicited by stimulation of the preganglionic vagal nerve fibres and by postganglionic (transmural) stimulation. The order of potency was NKA ≤ El > SP. Contractions induced by exogenous acetylcholine (ACh) were not increased by the tachykinins.
The magnitude of the tachykinin‐induced augmentation of responses to nerve stimulation was inversely related to stimulation voltage and frequency.
These results suggest that tachykinins act on NK2 receptors, both on the trachealis muscle and on postganglionic pulmonary parasympathetic nerve terminals. Activation of the neuronal receptors may increase the probability of transmitter release from the nerve terminals.
Effect of aminophylline on cisplatin nephrotoxicity in the rat
Authors: Heidemann H.Th. , Müller St. , Mertins L. , Stepan G. , Hoffmann K. , Ohnhaus E.E. 
Published: July 2012

The effect of the methylxanthine aminophylline on cisplatin (5 mg kg−1 i.v.)‐induced acute renal failure was investigated in the rat. Renal function was measured 5 days after cisplatin administration.
Cisplatin caused a polyuric acute renal failure. The creatinine clearance was significantly reduced.
Aminophylline (24 mg kg−1 12 h−1) ameliorated the cisplatin nephrotoxicity when administered during the maintenance phase of acute tubular necrosis. However, it had no effect when only administered prophylactically before the cisplatin application.
Enprofylline (20 mg kg−1 4 h−1 with dose adjustment), a methylxanthine lacking adenosine receptor antagonism in comparison to aminophylline, had no protective effect on cisplatin nephrotoxicity.
Adenosine is a renal vasoconstrictor and decreases glomerular filtration rate. Endogenous adenosine in the kidney is formed by degradation of ATP and is thought to be involved in various forms of acute renal failure. The results suggest that adenosine may be involved in the haemodynamic changes in the kidney induced by cisplatin.
Vasoactive actions of local anaesthetics on human isolated umbilical veins and arteries
Authors: Monuszko Eileen , Halevy Simon , Freese Kenneth , Liu‐Barnett Maida , Altura Burton 
Published: July 2012

An in vitro study, using helical preparations of human umbilical arteries and veins obtained from healthy women at term pregnancy, was designed to determine: (a) whether three local anaesthetics commonly utilized in obstetric anaesthesia (bupivacaine, 2‐chloroprocaine, and lignocaine) can induce contraction or relaxation of resting umbilical vessels; (b) whether these agents can induce contraction or relaxation of umbilical vessels which have been previously induced to contract by a known activator, potassium chloride (KCl); and (c) the relative potency of these agents as compared to KCl.
The results indicate that: (a) these local anaesthetics are vasoactive on human umbilical vascular smooth muscle; (b) bupivacaine induces contraction in over 90% of the resting vessels examined, while 2‐chloroprocaine consistently causes relaxation and lignocaine causes a small degree of contraction in 40% of vessels examined; (c) bupivacaine causes further contraction (or potentiation) of KCl‐contracted muscle in 50% of the vessels studied, while 2‐chloroprocaine and lignocaine both induce relaxation of these contracted vessels.
Tissue noradrenaline and the polyol pathway in experimentally diabetic rats
Authors: Lucas P.D. , Qirbi A. 
Published: July 2012

The effects of a six week period of streptozotocin‐induced diabetes on tissue catecholamines and on in vivo noradrenaline turnover were assessed in rats.
Noradrenaline concentrations measured in heart ventricle, terminal ileum, vas deferens, spleen and adrenal tissue from the diabetic rats were all found to be elevated compared to those found in control rat tissues. The adrenaline contents of the adrenal glands were also raised in these animals.
Noradrenaline turnover in heart ventricle, terminal ileum and vas deferens was estimated from the decline in tissue content of the amine following inhibition of its synthesis with α‐methyl‐p‐tyrosine. Turnover was found to be increased in all three tissues.
The involvement of the polyol pathway in the above changes was investigated by examining the effects of continuous treatment with an aldose reductase inhibitor, Statil (ICI 128436) or dietary myo‐inositol supplementation. Either treatment was found to prevent or reduce the increases in tissue noradrenaline and in its turnover. Myo‐inositol treatment also partially prevented the rise in adrenal adrenaline.
It is concluded that the elevation of tissue catecholamines and of noradrenaline turnover by diabetes was related to myo‐inositol depletion secondary to excessive sorbitol synthesis. Possible mechanisms for the observed increase in noradrenaline turnover could involve Na+, K+‐ATPase depression.
Limited interference of specific Paf antagonists with hyper‐responsiveness to Paf itself of lungs from actively sensitized guinea‐pigs
Authors: Pretolani Marina , Lefort Jean , Vargaftig B. Boris 
Published: July 2012

The interference of various platelet‐activating factor (Paf) antagonists with Paf‐ and antigen‐induced effects in isolated lungs from actively sensitized guinea‐pigs was investigated.
WEB 2086 and BN 52021, two antagonists structurally unrelated to Paf, at concentrations 10–100 fold above those exerting a potent and selective inhibition of the effects of Paf in lungs from non‐immunized guinea‐pigs, failed to inhibit bronchoconstriction and mediator release evoked by the phospholipid when administered into lungs from actively sensitized animals.
In contrast to WEB 2086 and BN 52021, antagonists such as Ro 19–3704 and Ro 19–1400, structurally related to the Paf molecule, at concentrations which abrogate the effects of Paf in lungs from non‐immunized guinea‐pigs, inhibited bronchoconstriction and release of histamine and leukotriene‐like material evoked by the intra‐arterial administration of Paf into lungs from actively sensitized animals.
Ro 19–3704 and Ro 19–1400 also inhibited markedly the release of leukotriene C4 (LTC4)‐like material and, to a smaller extent, the histamine secretion induced by 10 μg arachidonic acid.
CV 6209, another Paf antagonist structurally related to the phospholipid, failed to antagonize its bronchopulmonary and secretory effects in sensitized lungs.
All the antagonists used, irrespective of their ability to interfere or not with bronchoconstriction and mediator release triggered by Paf, suppressed oedema formation as measured by the increase in lung wet weight induced by either Paf or ovalbumin.
Our results indicate that: (i) the increase in vascular permeability and the subsequent oedema formation on one hand and the bronchopulmonary effects of Paf on the other hand are mediated by different mechanisms; and (ii) active sensitization provokes a marked modification of the lung reactivity to Paf.
Interaction of palmitoyl carnitine with calcium antagonists in myocytes
Authors: Patmore Leslie , Duncan Greig P. , Spedding Michael 
Published: July 2012

Beating of aggregates of embryonic chick myocytes, in primary culture, was quantified by use of a motion‐detector and video‐recorder technique. Interactions of palmitoyl carnitine, a putative endogenous ligand at Ca2+ channels, with calcium antagonists were investigated.
Bay K 8644 (1–100 nm) and palmitoyl carnitine (0.2–30 μm) increased edge movement of the aggregates; beats fused so that there was an increase in baseline ‘tone’. The concentrations required to produce a 50% increase in edge movement were 2.5 nm for Bay K 8644 and 2 μm for palmitoyl carnitine. Higher concentrations (20–30 μm) of palmitoyl carnitine caused tachycardia of abrupt onset but resulted in cessation of beating. The effects of palmitoyl carnitine were not stereo‐selective in that the (+)− and (−)‐isomers were equieffective. Lysophosphatidyl choline (LPC) had no effect in concentrations up to 10 μm but higher concentrations caused tachycardia followed by cessation of beating. High concentrations of both palmitoyl carnitine and LPC (100 μm) caused break‐up of the aggregates, presumably as a result of detergent effects.
Palmitoyl carnitine (1–100 μm) reversed the inhibitory effects of nisoldipine (0.3 μm), diltiazem (10 μm) and verapamil (1 μm). Ouabain was ineffective in reversing the effects of nisoldipine, differentiating the effects of palmitoyl carnitine from those of Na+/K+ATPase inhibition. In contrast, palmitoyl carnitine did not reverse the inhibitory effects of pimozide (2 μm) or lidoflazine (7 μm); palmitoyl carnitine showed a similar profile to Bay K 8644 in this respect.
These findings indicate that the effects of palmitoyl carnitine closely resemble those of Bay K 8644 and can be differentiated from those of lysophospholipids. As palmitoyl carnitine accumulates in the sarcolemma during myocardial ischaemia, the mode of action in the Ca2+ channel may have clinical relevance for the use of calcium antagonists in ischaemia.
Interference of WEB 2086 and BN 52021 with Paf‐induced effects on guinea‐pig trachea
Authors: Brunelleschi Sandra , Renzi Daniela , Ledda Fabrizio , Giotti Alberto , Fantozzi Roberto , Brink Charles , Benveniste Jacques 
Published: July 2012

The thienotriazolodiazepine WEB 2086 and the gingkolide BN52021 have been evaluated as antagonists of Paf‐acether (Pal) by studying their effects on Paf‐induced relaxation and Paf‐induced prostaglandin E2 (PGE2) production in histamine‐contracted guinea‐pig tracheal preparations.
Relaxation induced by Paf 4 μm in histamine‐contracted guinea‐pig tracheal preparations was 39.67 ± 3.5% (n = 30). At the same concentration, Paf significantly increased PGE2 production from histamine‐contracted guinea‐pig tracheal preparations.
WEB 2086 inhibited in a dose‐related manner (IC50 = 21.2 nm) the relaxant effect induced by Paf and, at 1 μm, suppressed Paf‐induced release of PGE2.
BN 52021 100 μm inhibited to about 60% Paf‐induced relaxation of histamine‐contracted guinea‐pig tracheal preparations, but completely abolished Paf‐induced increase in PGE2.
Both antagonists had no effects on relaxations induced by arachidonic acid 10 μm or PGE2 0.1–1 μm in histamine‐contracted guinea‐pig tracheal preparations.
The results are consistent with the presence of specific Paf receptors in guinea‐pig trachea and indicate that a relaxant prostanoid, namely PGE2, at least partially mediates Paf‐induced relaxation in this experimental model.
m‐Octopamine injected into the paraventricular nucleus induces eating in rats: a comparison with noradrenaline‐induced eating
Authors: Fletcher P.J. , Paterson I.A. 
Published: July 2012

The effects on food intake in rats of injection of m ‐and p‐octopamine into the paraventricular nucleus (PVN) of the hypothalamus were examined, and compared to the effects of noradrenaline (NA).
m‐Octopamine injected into the PVN induced a dose‐dependent increase in food intake, with the maximal effect occurring at a dose of 25 nmol. p‐Octopamine did not elicit eating unless it was administered to animals pretreated with the monoamine oxidase inhibitor, pargyline.
The effects of pretreatment with various adrenoceptor antagonists, injected into the PVN, on the eating responses induced by 25 nmol m‐octopamine and NA were examined. The α1‐adrenoceptor antagonist, corynanthine, and the β‐adrenoceptor antagonist, propranolol, failed to alter the eating induced by m‐octopamine or NA. The effects of these two amines were susceptible to blockade of α2‐adrenoceptors. Idazoxan reversed the eating induced by m‐octopamine and noradrenaline. However, yohimbine was effective only against the eating induced by m‐octopamine. Thus, both m‐octopamine and NA appear to act via α2, but not α1 or β‐adrenoceptors.
Injection of α‐methyl‐p‐tyrosine into the PVN attenuated the effect of m‐octopamine, but not of NA. This result suggests that m‐octopamine elicits eating, at least in part, by releasing endogenous NA.
The NA and octopamine uptake inhibitor, desipramine, significantly potentiated the eating induced by a low dose of m‐octopamine. This effect may occur because desipramine would prolong the synaptic activity of released NA.
The results indicate that m‐octopamine elicits a marked and reliable eating response which is mediated largely by a release of endogenous NA, which acts at α2‐receptors. These results are consistent with the view that octopamine may function as a modulator of NA activity in the central nervous system.
Inhibition of bradykinin‐induced bronchoconstriction in the guinea‐pig by a synthetic B2 receptor antagonist
Authors: Jin L.S. , Seeds E. , Page C.P. , Schachter M. 
Published: July 2012

Intravenous bradykinin (Bk) elicited bronchoconstriction in the anaesthetized ventilated guinea‐pig which was not mimicked by the B1 receptor agonist, des‐Arg9‐Bk.
Bradykinin‐induced bronchoconstriction was inhibited by the B2 receptor antagonist B4881, but not by the B1 receptor antagonist des‐Arg9‐Leu8‐Bk. The effect of B4881 was short‐lived.
The B2 receptor antagonist as B4881 was selective for bradykinin as B4881 did not significantly inhibit bronchoconstriction induced by i.v. bombesin, platelet activating factor, acetylcholine, histamine or vagal stimulation.
These results suggest that bradykinin‐induced bronchoconstriction in the guinea‐pig is via activation of a B2 receptor population and that B4881 is a selective B2 antagonist that may be useful for investigating the involvement of bradykinin in the lung.
Subclassification of α1‐adrenoceptor recognition sites by urapidil derivatives and other selective antagonists
Authors: Hanft Gertraud , Gross Gerhard 
Published: July 2012

The affinities of urapidil derivatives and other antagonists for α1‐adrenoceptors labelled by [3H]‐prazosin were determined on membranes of six different rat tissues.
Urapidil and its 5‐acetyl‐, 5‐formyl‐ and 5‐methyl‐derivative displaced [3H]‐prazosin from α1‐adrenoceptor binding sites in a concentration‐dependent manner which varied with tissue. IC50 values were lower in vas deferens, hippocampus and cerebral cortex than in heart, liver and spleen. For 5‐methyl‐urapidil, binding to two distinct sites could be demonstrated with mean K1 values of about 0.6 and 45 nM. Saturation binding studies with [3H]‐prazosin in the presence of 5‐methylurapidil indicated a competitive type of interaction between 5‐methyl‐urapidil and [3H]‐prazosin.
The proportion of [3H]‐prazosin binding sites with high affinity for 5‐methyl‐urapidil was 58% in vas deferens, 69% in hippocampus, 41% in cerebral cortex and 23% in myocardium. In liver and spleen virtually no high affinity sites were found. These values were in good agreement with the percentages of binding sites with high affinities for WB‐4101 and phentolamine, indicating that all these antagonists bind to the same subtype of α1 ‐recognition sites, whereas other α‐antagonists like BE 2254, yohimbine and unlabelled prazosin did not discriminate between two binding sites.
Preincubating membranes of the cerebral cortex with chloroethylclonidine preferentially inactivated [3H]‐prazosin binding sites with low affinity for 5‐methyl‐urapidil.
The antagonist potencies of 5‐methyl‐urapidil and WB‐4101 against α1‐adrenoceptor‐mediated contractile responses were higher in vas deferens than in myocardium. The α1‐mediated effects in vas deferens but not in the heart were highly susceptible to nitrendipine.
Using 5‐methyl‐urapidil, the existence of two distinct α1‐adrenoceptor recognition sites could be demonstrated which correspond to the proposed α1A‐ and α1B‐subtypes. Since 5‐methyl‐urapidil is one of the ligands with most selectivity between these subtypes in binding studies it may serve as a valuable tool for such investigations.
α1‐Adrenoceptor function and autoradiographic distribution in human asthmatic lung
Authors: Spina Dom , Rigby Paul J. , Paterson James W. , Goldie Roy G. 
Published: July 2012

The autoradiographic distribution of α1‐adrenoceptors was investigated in non‐diseased and asthmatic human lung by use of [3H]‐prazosin (H‐PZ). To validate binding and autoradiographic methods, H‐PZ binding was also measured in rat heart.
Significant levels of specific H‐PZ binding were detected in sections of rat heart. This binding was associated with a single class of non‐interacting sites of high affinity (dissociation constant, Kd = 1.17 ± 0.26 nm). The maximum binding capacity (Bmax) was 59.5 ± 4.5 fmol mg−1 protein.
In sharp contrast, very low levels of specific H‐PZ binding were found in both human non‐diseased and asthmatic bronchus, although a high level of binding of [125I]‐iodocyanopindolol (I‐CYP, 50 pm) to β‐adrenoceptors was detected in these airways. Furthermore, very low levels of autoradiographic grains representing specific H‐PZ binding were found in all airway structures in human non‐diseased or asthmatic lung parenchyma.
Consistent with these data, the α‐adrenoceptor agonist phenylephrine failed to induce significant increases in tone in bronchi isolated from either non‐diseased or asthmatic human lung. Results indicate that asthma does not involve significant increases in airway α1‐adrenoceptor function.
κ‐Opioid‐induced changes in renal water and electrolyte management and endocrine secretion
Authors: Ashton N. , Balment R.J. , Blackburn T.P. 
Published: July 2012

Subcutaneous injection of the κ‐opioid agonist U50,488 into conscious, saline‐loaded rats was associated with a diuresis, antinatriuresis and antikaliuresis which lasted for up to 3 h. Plasma renin activity and corticosterone levels were elevated but plasma vasopressin (AVP) and aldosterone levels were unaltered in similarly treated rats.
U50,488 administration to adrenal demedulated rats was not associated with a diuresis but produced an antinatriuresis, though sodium excretion rates were higher in demedullated than in sham‐operated animals. Plasma AVP and corticosterone levels were not affected by demedulation or subsequent U50,488 treatment. Sham‐operated, U50,488‐treated rats showed the expected increase in plasma corticosterone levels.
U50,488 administration resulted in an antidiuresis and an antinatriuresis in AVP‐deficient Brattleboro DI rats.
When coupled with fasting stress U50,488 administration resulted in similar but attenuated renal responses compared with those observed in unfasted rats. Basal plasma corticosterone levels were elevated in fasted animals and were further increased by U50,488.
Both water and electrolyte handling by the kidney are altered by U50,488. The diuretic effects of U50,488 were reversed by adrenal demedullation and in the absence of endogenous AVP, but the antinatriuretic actions were not altered, suggesting that the effects upon renal water and electrolyte excretion may be mediated by separate mechanisms.
The effect of atrial natriuretic peptide on human isolated resistance arteries
Authors: Hughes A.D. , Nielsen H. , Sever P.S. 
Published: July 2012

The action of (1–28) α‐human atrial natriuretic peptide (ANP) was studied on human isolated resistance arteries.
Renal, skeletal muscle, omental and subcutaneous resistance arteries were taken from tissue removed at surgery and isometric tension responses were measured with a myograph.
ANP (10−9–10−6m) relaxed precontracted segments of renal and skeletal muscle arteries in a concentration‐dependent manner. ANP failed to relax isolated omental or subcutaneous arteries.
The effect of ANP on human isolated resistance arteries varies depending on the site of origin of the artery.
Sodium pentobarbitone enhances responses of thalamic relay neurones to GABA in rat brain slices
Authors: Sykes T.C.F. , Thomson Alex M. 
Published: July 2012

In rat isolated thalamic slices, intracellular recordings were made of responses to electrophoretically applied γ‐aminobutyric acid (GABA) in the absence and presence of sodium pentobarbitone (NaPb).
Responses to electrophoretically applied GABA were biphasic in the majority of neurones studied. They consisted of an early, negative‐going and later, positive‐going phase, when recorded close to reversal potential.
An increase in the GABA ejection current caused an enhancement of the late positive‐going phase, along with a shift in the reversal potential of the whole response to a more positive value. These changes were accompanied by an increase in GABA‐induced conductance (decrease in resistance) and an increase in the duration of the response.
Application of NaPb to the GABA response produced similar effects, namely an enhancement of the late positive‐going phase, a shift in the reversal potential to a more positive value, an increase in conductance and an increase in duration.
GABA‐mediated inhibitory postsynaptic potentials (i.p.s.ps) were evoked by electrical stimulation of the nucleus reticularis thalami. Application of NaPb caused an increase in the duration of the i.p.s.p. and a shift in its reversal potential to a more positive value.
Sympathetic vascular control of the pig nasal mucosa: adrenoceptor mechanisms in blood flow and volume control
Authors: Lacroix Jean‐Silvain , Lundberg Jan M. 
Published: July 2012

The adrenoceptor mechanisms influencing the total blood flow, volume and superficial blood flow in the nasal mucosa of pigs anaesthetized with pentobarbitone have been characterized by use of various agonists and antagonists.
Local intra‐arterial bolus injection of the selective α1‐agonist phenylephrine, the selective α2‐agonist UK 14.304, the mixed α1/α2‐agonist oxymetazoline and the mixed α/β‐agonists noradrenaline (NA) and adrenaline induced dosed‐related reduction of nasal arterial blood flow (BF), nasal mucosal volume (V, reflecting capacitance vessel function) and the laser Doppler flowmetry signal (LDF, reflecting superficial movement of blood cells). The rank order of α‐agonist potency regarding BF reduction was UK 14.304 > oxymetazoline > NA > phenylephrine = adrenaline. For the volume response the potency order was UK 14.304 > oxymetazoline = NA = adrenaline > phenylephrine while for the reduction of the LDF signal the potency was UK 14.304 = NA = adrenaline > oxymetazoline > phenylephrine. The selective β2‐agonist terbutaline caused dose‐dependent increase of BF whereas only a small augmentation of the V was obtained upon the highest dose (40 nmol) while no modification of the LDF signal was observed.
After pretreatment with the selective α1‐antagonist prazosin, the response to phenylephrine was abolished while the selective α2‐antagonist idazoxan attenuated the effect of UK 14.304. After pretreatment with α‐antagonists, both NA and adrenaline caused biphasic effects with constriction followed by vasodilatation for BF, but not for V or LDF. This vasodilatation was blocked by the β‐antagonist propranolol.
The reduction in nasal BF and V upon sympathetic nerve stimulation was attenuated both by prazosin and idazoxan. Propranolol enhanced the remaining reduction of BF but not of V in the presence of α‐antagonists.
It is concluded that α2‐adrenoceptor mechanisms in the pig nasal mucosa are dominating for the BF, V and LDF responses to exogenous agonists, α1‐Adrenoceptors also seem to be involved in the sympathetic control of BF, V and LDF. Activation of β2‐receptors increases mainly BF and does not influence the LDF signal.