bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential release of eicosanoids by bradykinin, arachidonic acid and calcium ionophore A23187 in guinea‐pig isolated perfused lung
Authors: Bakhle Y.S. , Moncada S. , DE Nucci G. , Salmon J.A. 
Published: July 2012

The effects of infusions of bradykinin (0.2 μM), calcium ionophore A23187 (0.5 μM) and arachidonic acid (13 μM) on the release of eicosanoids from the guinea‐pig isolated perfused lung were investigated using radioimmunoassay for thromboxane B2 (TXB2), 6‐oxo‐prostaglandin F1α (6‐oxo‐PGF1α), PGE2, leukotriene B4 (LTB4) and LTC4 and bioassay using the superfusion cascade.
Bradykinin released more 6‐oxo‐PGF1α than TXB2, whereas arachidonic acid and ionophore released more TXB2 than 6‐oxo‐PGF1α.
The time course of eicosanoid release varied with the stimulus: bradykinin and arachidonic acid produced an immediate release, whereas the ionophore showed a slower onset of release.
Although the amounts of LTB4 and LTC4 released by the ionophore were very low according to radioimmunoassays, there was evidence from the bioassay of release of a leukotriene‐like substance, thought to be LTD4.
The leukotriene antagonist FPL 55712 lacks specificity in the guinea‐pig trachea; at the concentration used (2 μM) it antagonized contractions of the tracheal strip to PGE2 as well as to LTC4.
Our results show that in the guinea‐pig perfused lung the metabolism of exogenous arachidonic acid is both qualitatively and quantitatively different from the metabolism of endogenous arachidonic acid; furthermore, the profile of eicosanoid production is stimulus‐dependent.
Adenosine‐induced secretion in the canine trachea: modification by methylxanthines and adenosine derivatives
Authors: Johnson Herbert G. , McNee Martha L. 
Published: July 2012

Adenosine alone at 0.1 and 1.0 mg per tracheal segment stimulated mucus secretion by 52% and 88%, respectively, compared to baseline (P < 0.0001).
The site of the potent secretagogue effect of adenosine in canine trachea was consistent with A2 activation.
A2 site activation and enhanced secretion were also induced by N‐ethylcarboxamide adenosine and dipyridamole.
N6‐R‐phenylisopropyl adenosine (PIA) and 2′,5′‐dideoxyadenosine (ddAdo) inhibited the adenosine‐induced secretion (35% and 42%, respectively). However, when PIA or ddAdo were administered in conjunction with the potent phosphodiesterase inhibitor, methylisobutylxanthine (MIX), the effects of PIA were potentiated and the effects of ddAdo were reversed, yielding stimulation (A2) and antagonism (A1) of secretion, respectively.
8‐Phenyltheophylline by aerosol was a very potent antagonist of the secretagogue effect of adenosine (70% inhibition; P < 0.00001).
The influence of blood gases on α1‐ and α2‐adrenoceptor‐mediated pressor responses in the pithed rat
Authors: Grant T.L. , McGrath J.C. , O'Brien J.W. 
Published: July 2012

The influence of blood gases on α1‐ and α2‐adrenoceptor‐mediated pressor responses was studied in the pithed rat by varying the inspired gas mixture or the ventilation stroke volume.
Acidosis favoured the peak responses to the α2‐adrenoceptor agonist, xylazine, while alkalosis favoured the peak responses to the α1‐adrenoceptor agonist, phenylephrine. A combination of hypoxia and hypercapnia greatly depressed the α1 response to phenylephrine whereas the α2 response to xylazine remained relatively unaffected.
When PaO2 was varied in either acidotic or alkalotic conditions the response to the phenylephrine increased as PaO2 increased.
To prevent hypoxia in air ventilated rats, large stroke volumes were required. This caused alkalosis and hence decreased responsiveness to xylazine. Consequently, air ventilated pithed rats gave poorer responses to xylazine than did those ventilated on 100% O2.
The results show that α1‐ and α2‐adrenoceptor‐mediated pressor responses can be differentially affected by blood gases. The relative contribution of α1‐ and α2‐adrenoceptors to vascular tone may be either under‐ or over‐estimated depending on the arterial blood gases.
The effects of sodium nitroprusside and 8‐bromo‐cyclic GMP on electrical and mechanical activities of the rat tail artery
Authors: Cheung D.W. , MacKay M.J. 
Published: July 2012

The effects of sodium nitroprusside and 8‐bromo‐guanosine 3′:5′‐cyclic monophosphate (8‐bromocyclic GMP) on the electrical and mechanical activities of the rat tail artery were compared.
The inhibitory effects of sodium nitroprusside on the contractions induced by noradrenaline, phenylephrine, KCl and clonidine were mimicked by 8‐bromo‐cyclic GMP.
Sodium nitroprusside and 8‐bromo‐cyclic GMP increased the resting membrane potential only in preparations with low initial resting membrane potentials.
In tissues previously contracted and depolarized with noradrenaline, KCl and clonidine, both sodium nitroprusside and 8‐bromo‐cyclic GMP caused relaxation without significantly affecting the membrane potential.
Both sodium nitroprusside and 8‐bromo‐cyclic GMP abolished neurally‐mediated contractions without any significant effect on the electrical responses.
These results suggest that the actions of sodium nitroprusside and 8‐bromo‐cyclic GMP are not related to membrane hyperpolarization or inhibition of membrane excitability.
[3H]‐tetracaine binding on rat synaptosomes and sodium channels
Authors: Grima Michèle , Schwartz Jean , Spach Marie‐Odile , Velly Jeanne 
Published: July 2012

[3H]‐tetracaine binding was studied in a rat synaptosomal preparation. [3H]‐tetracaine bound to a single class of binding sites with a mean KD of 188 ± 28 nM and a mean maximal binding capacity of 13 ± 0.7 pmol mg−1 protein.
[3H]‐tetracaine binding was inhibited by tetracaine, procaine and by β‐adrenoceptor blocking agents which possess local anaesthetic properties.
[3H]‐tetracaine binding was not modified by neurotoxins interacting specifically with the sodium channels.
Experimental testing of Mackay's model for functional antagonism in the isolated costo‐uterus of the rat
Authors: Henry Peter J. , Lulich Karmelo M. , Paterson James W. 
Published: July 2012

Several key predictions of a recently developed model for functional antagonism (Mackay, 1981) were experimentally tested using the rat isolated costo‐uterine preparation.
In the presence of the functional antagonist fenoterol (Fen), the functional affinity constants (KAF) for carbachol and oxotremorine (Oxo) were respectively 9.9 and 3.4 fold greater than their corresponding affinity constants (KA). According to Mackay's model for functional antagonism, the higher KAF/KA ratio for carbachol indicates that this cholinoceptor agonist has a greater efficacy than Oxo. This was confirmed by using conventional pharmacological methods.
As predicted from the model of functional antagonism, the plot of KAF/KA ‐ 1 against the fraction of cholinoceptors not irreversibly blocked by phenoxybenzamine (Pbz) was linear for both carbachol and Oxo and the lines of best fit crossed the axes at a point not significantly different from the origin.
The value of 4.6 for the relative efficacy of carbachol to Oxo estimated from functional antagonism studies was comparable to the value of 5.6 calculated using the method of irreversible antagonism proposed by Furchgott (1966).
Frequency‐dependent block of field potentials in the rat hippocampal slice caused by tricyclic antidepressants
Authors: Anwyl R. , Rowan M.J. 
Published: July 2012

The effect of the tricyclic antidepressants imipramine and desipramine were studied on field potentials in the rat hippocampal slice. The electrically evoked stratum radiatum nerve volley, excitatory postsynaptic potential (e.p.s.p.) and pyramidal cell layer population spike (PS) were recorded in the CA1 region.
At concentrations of 10−6 M to 10−5 M, impramine did not affect the amplitude of the nerve volley, e.p.s.p. or PS at low frequencies of stimulation (0.01 Hz). At higher frequencies of stimulation (1–100 Hz), imipramine caused a frequency‐dependent block of the nerve volley, e.p.s.p. and PS.
The time course of onset of the frequency‐dependent block in the presence of imipramine was very slow. Maximum inhibition was reached after 3–4 h treatment with imipramine.
Desipramine (10−6–10−5 M) also caused a frequency‐dependent block of the hippocampal field potentials.
Only slight frequency‐dependent block was observed in slices from rats injected in vivo with desipramine (10 mg kg−1) for 14 days.
Galanin: neuromodulatory and direct contractile effects on smooth muscle preparations
Authors: Ekblad E. , Håkanson R. , Sundler F. , Wahlestedt C. 
Published: July 2012

The effects of galanin, a newly isolated neuropeptide, and of a galanin fragment (galanin 1–10) were studied on various smooth muscle preparations in vitro. Direct motor effects as well as effects on electrically induced (neuronally mediated) responses (neuromodulatory effects) were observed.
Both gatanin and galanin 1–10 evoked a strong contractile response in rat jejunal longitudinal muscle. This effect was a direct one on the smooth muscle.
Addition of galanin to guinea‐pig taenia coli inhibited the contractile responses to electrical stimulation, mediated by endogenous substance P and acetylcholine. In the rabbit iris sphincter, galanin reduced the acetylcholine‐mediated but not the substance P‐mediated contraction evoked by electrical stimulation. The neuromodulatory effects seem to be presynaptic and require the whole or possibly only the C‐terminal part of the galanin molecule, since galanin 1–10 was ineffective.
Rabbit femoral artery and vein, gastroepiploic and basilar arteries and guinea‐pig trachea and main bronchi did not respond to either galanin or galanin 1–10.
Analysis of the α‐adrenoceptor‐mediated, and other, components in the sympathetic vasopressor responses of the pithed rat
Authors: Flavahan N.A. , Grant T.L. , Greig J. , McGrath J.C. 
Published: July 2012

The vascular receptors activated following sympatho‐adrenal stimulation were determined by analysing the effects of ‘selective’ antagonists on the vasopressor response to spinal sympathetic nerve activation in the pithed rat.
The net vascular response to adrenal stimulation was a balance between α‐adrenoceptor‐mediated vasoconstriction and β‐adrenoceptor‐mediated vasodepression. Part of the α‐adrenoceptor‐mediated response was ‘prazosin‐sensitive’ (α1) and the remainder was abolished by rauwolscine (α2).
As with adrenal stimulation, direct sympathetic nerve stimulation of the vasculature evoked pressor responses which were partly resistant to prazosin. Rauwolscine only partly blocked the prazosin‐sensitive component. Reserpine pretreatment led to smaller responses than prazosin plus rauwolscine. Thus, the response resistant to α‐adrenoceptor antagonists could be mediated, in part, by adrenoceptors distinct from α‐adrenoceptors, as currently defined.
α, β‐Methylene ATP reduced the nerve‐mediated pressor response after α‐adrenoceptor blockade or reserpine pretreatment but not in drug‐free controls.
The results suggest that stimulation of the adrenal medulla can produce a vasopressor response which consists of summating α1 and α2‐adrenoceptor‐mediated components, and is identical to the effect of injected adrenaline. In contrast, the response to vasopressor nerve stimulation appears to be essentially mediated by α1‐adrenoceptors, with a facilitatory influence from α2‐adrenoceptors. A further response obtained after α‐adrenoceptor blockade may contain a purinergic component and another which is adrenergic but not mediated by stimulation of α‐adrenoceptors.
Modulation of 5‐hydroxytryptamine‐induced head‐twitch response by drugs acting at GABA and related receptors
Authors: Handley Sheila L. , Singh Lakhbir 
Published: July 2012

The effects of drugs acting at the γ‐aminobutyric acid (GABA) receptors and other chloride ionophore‐related sites have been studied for their ability to modulate the head‐twitch induced by 1–5‐hydroxytryptophan (5‐HTP) in the mouse.
The GABAa receptor agonists, muscimol, imidazoleacetic acid and 3‐aminopropanesulphonic acid, produced a dose‐related potentiation, while bicuculline inhibited the head‐twitch. The GABAb receptor agonist, baclofen, produced dose‐related inhibition.
Diazepam potentiated the head‐twitch while the ‘inverse’ benzodiazepine receptor agonist ethyl‐β‐carboline‐3‐carboxylate inhibited the head‐twitch. The antagonist Ro15‐1788 also produced inhibition. Ro05‐4864, a ligand for the benzodiazepine ‘acceptor’ site, potentiated the head‐twitch.
Pentobarbitone and pentylenetetrazol potentiated the 5‐HTP‐induced head‐twitch at low doses, changing to inhibition as the dose was increased. Picrotoxin in subconvulsant doses, produced only potentiation. More than one site may be involved in the action of these substances.
GABA, amino‐oxyacetic acid and 1–2‐4‐diaminobutyric acid inhibited the head‐twitch, while the GABA‐depletor, 3‐mercaptopropionic acid potentiated it.
Of all the agents tested, only muscimol produced head‐twitching when given alone.
It was concluded that both GABAa and GABAb receptors modulate the head‐twitch response to 5‐HTP.
Effects of lidocaine, procaine, procainamide and quinidine on electrophysiological properties of cultured embryonic chick hearts
Authors: Neto Francisco Riccioppo , Sperelakis Nicholas 
Published: July 2012

The effects of lidocaine, procaine, procainamide and quinidine were studied on organ‐cultured embryonic chick (2–3 day‐old) ventricular cells.
Lidocaine (10−5 − 10−4 M), in a dose‐dependent manner, reduced the rate of pacemaker discharge, the action potential amplitude (APA), the maximum rate of rise (Vmax) of the upstroke of the action potential and the action potential duration at 50% repolarization (APD50). These changes occurred without alterations in the maximum diastolic potential (MDP). Extracellular electrical field stimulation could still evoke action potentials in cells arrested by 10−4 M lidocaine, but 10−3 M lidocaine completely abolished electrical activity.
Procaine, procainamide and quinidine, at 5 × 10−5 M to 10−3 M, depolarized the cells to around − 30 mV and reduced APA and Vmax. Procaine and procainamide increased APD50, but quinidine shortened it. All the effects described disappeared completely in about 40 min of superfusion with drug‐free Tyrode solution.
Isoprenaline (5 × 10−7 M) and adrenaline (10−6 M) restored spontaneous firing of preparations arrested by any of the antiarrhythmic agents and repolarized ventricular cells depolarized by procaine, procainamide or quinidine. Propranolol (5 × 10−7 M) did not affect the depolarization produced by procaine (5 × 10−4 M), but antagonized its reversal by isoprenaline.
In contrast, isoprenaline (10−6 M) did not produce recovery of automaticity of preparations arrested by verapamil (10−5 M).
Histamine (10−5 M) or strontium (10 mM) were not able to restore rhythmic activity in cells arrested procaine.
Application of long (10–15 s duration) hyperpolarizing currents did not reverse the blocking effect of procaine, procainamide and quinidine.
The input resistance increased during the procaine‐induced depolarization.
It is suggested that the four agents studied block the slow Na+ channels responsible for the upstroke of the action potential in young chick heart cells. A drug‐induced decrease in PK may occur in those cells arrested at low levels of membrane potential.
Electrophysiological and other aspects of the relaxant action of isoprenaline in guinea‐pig isolated trachealis
Authors: Allen S.L. , Beech D.J. , Foster R.W. , Morgan G.P. , Small R.C. 
Published: July 2012

In guinea‐pig isolated trachealis isoprenaline (0.001‐0.1 μmol 1−1) caused concentration‐dependent relaxation. Propranolol (1μmol 1−1) antagonized the effects of isoprenaline by more than 100 fold but did not modify the relaxant action of sodium nitrite.
The tracheal relaxant actions of isoprenaline and ATP were unaffected by apamin (0.1 μmol 1−1) but apamin profoundly antagonized the effects of noradrenaline and ATP on guinea‐pig isolated taenia caeci.
Tetraethylammonium (TEA; 8 mmol 1−1) and procaine (5 mmol 1−1) each evoked tracheal spasm but neither agent antagonized the isoprenaline‐evoked relaxation of the trachealis.
Trachealis exposed to K+‐rich (120 mmol 1−1) Krebs solution developed near‐maximal tension. Both isoprenaline and sodium nitrite relaxed the K+‐depolarized tissue though concentration‐effect curves for both relaxants were moved to the right compared to those obtained in non‐depolarized tissues. The maximal effect of sodium nitrite was markedly reduced.
Intracellular electrophysiological recording showed that isoprenaline (0.01–1 μmol 1−1) caused hyperpolarization and reduced or abolished slow wave discharge in trachealis muscle. These effects were accompanied by relaxation. Propranolol (1 μmol 1−1) virtually abolished both the electrical and mechanical responses to isoprenaline (0.1 μmol 1−1).
Apamin (0.1 μmol 1−1) did not alter the spontaneous electrical activity of trachealis cells or their electrical and mechanical responses to isoprenaline (0.1 μmol 1−1).
TEA (8 mmol 1−1) caused depolarization and often increased slow wave amplitude and induced spike discharge. Isoprenaline (0.01 μmol 1−1) failed to hyperpolarize TEA‐treated trachealis cells. Higher concentrations of isoprenaline suppressed TEA‐induced spasm, caused hyperpolarization and thereby increased slow wave or spike amplitude. Slow wave or spike frequency decreased as the hyperpolarization progressed but abolition of slow waves or spikes sometimes required more than 4 min exposure to isoprenaline.
Procaine (5 mmol 1−1) increased the amplitude of slow waves and induced spike discharge. Procaine markedly reduced the hyperpolarization induced by isoprenaline (0.1 and 1 μmol 1−1) but had little effect on isoprenaline‐induced relaxation.
It is concluded that isoprenaline activates β‐adrenoceptors in guinea‐pig trachealis and thereby evokes relaxation and hyperpolarization of the smooth muscle. The hyperpolarization does not involve the opening of apamin‐sensitive K+‐channels and it probably plays a supportive rather than a crucial role in the process by which isoprenaline‐induced relaxation is achieved.
Neuromuscular blocking agents inhibit receptor‐mediated increases in the potassium permeability of intestinal smooth muscle
Authors: Gater P.R. , Haylett D.G. , Jenkinson D.H. 
Published: July 2012

The neuromuscular blocking agents tubocurarine, atracurium and pancuronium have been tested for their ability to inhibit receptor‐mediated increases in the K+ permeability of intestinal smooth muscle.
All three agents, as well as the bee venom peptide apamin, reduced both the resting efflux of 86Rb and the increase in efflux caused by the application of either bradykinin (1 μM) or an α1‐adrenoceptor agonist, amidephrine (20 μM), to depolarized strips of guinea‐pig taenia caeci. This suggested that, like apamin, the neuromuscular blocking agents inhibit the Ca2+‐dependent K+ permeability (PK(Ca)) mechanism which in this tissue is activated by a variety of membrane receptors.
The concentrations (IC50s) of atracurium, pancuronium and (+)‐tubocurarine which reduced the effect of amidephrine on 86Rb efflux by 50% were 12, 37 and 67 μM respectively.
Also in keeping with an ability to block PK(Ca), the neuromuscular blockers and apamin reduced the inhibition by amidephrine and bradykinin of physalaemin‐mediated contractions of the taenia caeci. The IC50 values were 15, 31 and 120 μM for atracurium, tubocurarine and pancuronium respectively, and 2.3 nM for apamin.
Each of the neuromuscular blockers, and apamin, increased the spontaneous contractions of the rabbit duodenum and blocked the inhibitory effect of amidephrine thereon.
It is concluded that the PK(Ca) mechanism in the longitudinal smooth muscle of the intestine resembles that of hepatocytes and sympathetic ganglion cells in its susceptibility to inhibition by neuromuscular blocking agents, as well as by apamin.
Mechanism of gastric antisecretory effect of SCH 28080
Authors: Beil W. , Hackbarth I. , Sewing K.‐Fr. 
Published: July 2012

The mechanism of the gastric antisecretory action of SCH 28080 has been studied utilizing two different in vitro test systems, isolated and enriched parietal cells from the guinea‐pig and guinea‐pig gastric membranes purified and enriched with K+/H+‐ATPase.
In guinea‐pig isolated and enriched parietal cells SCH 28080 inhibited the acid response to histamine and high K+ concentrations with IC50 values not significantly different from each other.
SCH 28080 inhibited the purified K+/H+‐ATPase measured in the presence of 5 mM KCl with an IC50 value of 1.3 μM. Kinetic studies indicated a competitive inhibition of ATPase by SCH 28080 with respect to K+. Studies on Na+/K+‐ATPase showed that this enzyme was only slightly depressed by SCH 28080.
It is concluded that SCH 28080 acts with high selectivity on the parietal cell K+/H+‐ATPase, establishing its antisecretory effect by a competitive interaction with the high affinity K+‐site of the gastric ATPase.
The effect of chronic neostigmine treatment on channel properties at the rat skeletal neuromuscular junction
Authors: Gwilt M. , Wray D. 
Published: July 2012

We have studied the effects of chronic neostigmine treatment on single channel properties at the rat skeletal neuromuscular junction. Rats received 0.86 mg kg−1 neostigmine (s.c.) daily for 9–11 days. Microelectrode recordings were then made from the extensor digitorum longus muscle.
The amplitude of miniature endplate potentials was significantly reduced in muscles from neostigmine‐treated rats as compared with controls.
Acetylcholine (2–5 μM) applied in the bath produced a depolarization and associated channel opening frequency (from voltage noise analysis) which were significantly reduced in neostigmine‐treated muscles with respect to controls.
The depolarization resulting from the opening of a single channel (from voltage noise analysis) and single channel open time and conductance (from current noise analysis) were not significantly changed by chronic neostigmine treatment.
It is concluded that chronic neostigmine treatment causes an adaptive reduction in the number of functional acetylcholine receptors at the endplate without otherwise affecting single channel properties themselves.
Thyroxine treatment of aged or young rats demonstrates that vascular responses mediated by β‐adrenoceptor subtypes can be differentially regulated
Authors: O'Donnell Stella R. , Wanstall Janet C. 
Published: July 2012

Responses to vascular relaxant drugs were obtained on KCl (15 mM)‐contracted isolated ring preparations of pulmonary artery and aorta from young (1–2 months old) and aged (> 16 months old) rats. These vessels contain both β1‐ and β2‐adrenoceptors.
Relaxant responses (i.e. relaxation expressed as a % of the KCl‐induced contraction) to isoprenaline, procaterol (β2‐seleotive partial agonist), fenoterol (β2‐selective) and noradrenaline (β1‐selective) but not those to forskolin, 3‐isobutyl‐1‐methylxanthine, enprofylline or sodium nitrite, were smaller on preparations from aged rats than on those from young rats.
Thyroxine (T4)‐treatment (1 mg kg−1 s.c. thrice weekly for 3–5 weeks) of aged or young rats enhanced responses to isoprenaline and noradrenaline but reduced those to procaterol, when compared with preparations from age‐matched saline‐treated control rats.
The agonist order of potency, determined in young rats, was isoprenaline>noradrenaline>adrenaline in preparations from T4‐treated rats compared with isoprenaline > adrenaline > noradrenaline in saline‐treated control rats.
It is concluded (a) that the age‐related decline in vascular responses to β‐adrenoceptor agonists involves β‐adrenoceptor mechanisms specifically and possibly β2‐adrenoceptors more than β1‐adrenoceptors; and (b) that T4‐treatment of rats enhances β1‐adrenoceptor‐mediated and reduces, or does not change, β2‐adrenoceptor‐mediated responses of preparations of rat pulmonary artery and aorta. In preparations from control rats β2‐adrenoceptors were functionally predominant but in preparations from T4‐treated rats β1‐adrenoceptors appeared to become functionally predominant.