bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relaxing actions of procaterol, a β2‐adrenoceptor stimulant, on smooth muscle cells of the dog trachea
Authors: Fujiwara T. , Sumimoto K. , Itoh T. , Suzuki H. , Kuriyama H. 
Published: July 2012

The effects of procaterol, a β2‐adrenoceptor agonist, on smooth muscle cells of the dog trachea were investigated by use of microelectrode and isometric tension recording methods, and by measurement of Ca transients as estimated fromthe fura‐2 fluorescence, adenosine 3′: 5′‐cyclic monophosphate (cyclic AMP) and breakdown of phosphatidylinositols.
Procaterol hyperpolarized the membrane and increased the ionic conductance (above 10 nm) in a dose‐dependent manner. These actions were inhibited by propranolol.
Procaterol inhibited the mechanical responses evoked by acetylcholine (ACh), histamine or 5‐hydroxytryptamine (5‐HT), in the presence or absence of Ca2+ in the bath solution, but not that evoked by high concentrations of ACh (1 μm). The ID50 value of procaterol for the peak amplitude of the ACh‐induced contraction (30 nm) was 0.3 nm. The equivalent values for the histamine‐induced phasic and tonic responses (10 μm) were 0.15 and 0.01 nm), respectively.
Procaterol (over 1 nm) increased the amount of cyclic AMP in a dose‐dependent manner which was blocked by prior application of propranolol.
Procaterol did not alter the changes in the amounts of phosphatidylinositol 4,5‐bisphosphate (PI‐P2) and phosphatidic acid (PA) induced by ACh, histamine or 5‐HT. Thus, the synthesis of inositol 1,4,5‐trisphosphate is not affected by stimulation of the β2‐adrenoceptor.
ACh increased the free Ca2+ concentration to a greater extent than that produced by histamine or 5‐HT. These changes were reduced by procaterol, except for those induced by high concentrations of ACh (over 1 μm).
It is concluded that procaterol relaxes tissues precontracted by various agonists due to a reduction in the free Ca2+. This inhibitory action may be due to an increase in the amount of cyclic AMP but does not result from an inhibition of the hydrolysis of phosphatidyl inositols. The hyperpolarization induced by procaterol may partly contribute to the observed relaxation.
Effects of the potassium channel blocking dendrotoxins on acetylcholine release and motor nerve terminal activity
Authors: Anderson A.J. , Harvey A.L. 
Published: July 2012

The effects of the K+ channel blocking toxins, the dendrotoxins, on neuromuscular transmission and motor nerve terminal activity were assessed on frog cutaneous pectoris, mouse diaphragm and mouse triangularis sterni nerve‐muscle preparations. Endplate potentials (e.p.ps) and miniature e.p.ps were recorded with intracellular microelectrodes, and nerve terminal spikes were recorded with extracellular electrodes placed in the perineural sheaths of motor nerves.
Dendrotoxin from green mamba (Dendroaspis angusticeps) venom and toxin I from black mamba (D. polylepis) venom increased the amplitude of e.p.ps by increasing quantal content, and also induced repetitive e.p.ps.
Perineural recordings revealed that dendrotoxins could decrease the component of the waveform associated with K+ currents at the nerve terminals, and induce repetitive activation of nerve terminals.
In frog motor nerves, dendrotoxins are known to block the fast f1 component of the K+ current at nodes of Ranvier. Blockade of a similar component of the K+ current at motor nerve terminals may be responsible for the effects of these toxins on neuromuscular transmission.
Similar conclusions can be drawn from the results obtained from mouse neuromuscular junctions.
Antagonism of N‐methylaspartate and synaptic responses of neurones in the rat ventrobasal thalamus by ketamine and MK‐801
Authors: Salt T.E. , Wilson D.G. , Prasad S.K. 
Published: July 2012

Extracellular single neurone recordings were made in the ventrobasal thalamus of urethaneanaesthetized rats.
Iontophoretically and intravenously administered ketamine and MK‐801 were found to be selective antagonists of responses of neurones to iontophoretically applied N‐methylaspartate.
Both antagonists, administered in N‐methylaspartate‐selective quantities, reduced the synaptic responses of ventrobasal thalamus neurones to a two‐second air jet directed at the peripheral receptive field.
Evidence for depressant 5‐HT1‐like receptors on rat brainstem neurones
Authors: Davies Michael , Wilkinson Lawrence S. , Roberts Malcolm H.T. 
Published: July 2012

The technique of microiontophoresis was used to evaluate the contribution of 5‐HT1‐like, 5‐HT2‐ and 5‐HT3‐receptors to the depressant effects of 5‐hydroxytryptamine (5‐HT) on neurones in the midline of the medullary brainstem of the rat in vivo.
Depressant responses to 5‐HT were resistant to antagonism by the 5‐HT2‐receptor antagonist ketanserin and the 5‐HT3‐receptor antagonist MDL 72222 applied either microiontophoretically or administered systemically.
Microiontophoretic or systemic administration of the 5‐HT antagonist metergoline, which shows nanomolar affinity for the 5‐HT1‐binding site, also failed to attenuate the depressant responses to 5‐HT.
Systemic administration of high doses of methysergide (30–40 mg kg−1) attenuated the depressant responses to 5‐HT but did not block depressant responses to GABA or excitatory responses to glutamate.
The depressant effects of 5‐HT were potently mimicked by the 5‐HT1‐like receptor agonists 5‐carboxamidotryptamine and 8‐OH‐DPAT.
These results indicate that neither 5‐HT2‐receptors nor 5‐HT3‐receptors are involved in the depressant effects of 5‐HT on midline brainstem neurones. The depressant effects of 5‐carboxamidotryptamine (5‐CT) and 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) and blockade of the response to 5‐HT by high doses of methysergide suggests the involvement of 5‐HT1‐like receptors. The lack of effect of metergoline, however, indicates that this receptor may be different from any of the 5‐HT1 binding sites yet described.
Effects of neostigmine and physostigmine on the acetylcholine receptor‐ionophore complex in frog isolated sympathetic neurones
Authors: Jun‐Ichi Sadoshima , Tokutomi Naofumi , Akaike Norio 
Published: July 2012

The effects of neostigmine and physostigmine, reversible carbamate acetylcholinesterase (AChE)‐inhibitors, on nicotinic acetylcholine‐induced inward currents (IACH) were investigated in enzymatically isolated single sympathetic ganglion cells from the bullfrog. The ‘concentration clamp’ technique which combines intracellular perfusion with a rapid external solution change under single electrode voltage‐clamp conditions was used.
Pretreatment with neostigmine and physostigmine did not enhance IAch at any concentrations, suggesting that AChE activity had already disappeared during the enzymatic treatment of the preparation.
Both neostigmine and physostigmine inhibited IAch in a dose‐dependent manner with IC50 values of 7.0 × 10−4 m and 1.1 × 10−4 m, respectively. The blockade by neostigmine was competitive, while that by physostigmine was non‐competitive.
The inhibition of IAch by neostigmine and physostigmine showed no apparent voltage dependency.
Neostigmine did not cause obvious changes of the kinetics of IAch. However, physostigmine reduced both the fast and slow time constants of inactivation of IAch, thus facilitating the rate of inactivation without affecting the activation kinetics of IAch.
These results suggest that neostigmine and physostigmine have different direct actions on the ACh receptor‐ionophore complex. Neostigmine may act on the ACh‐receptor (the binding site of ACh) while physostigmine may interact with the ACh‐gated cation channels.
Neonatal capsaicin treatment of rats reduces ACTH secretion in response to peripheral neuronal stimuli but not to centrally acting stressors
Authors: Donnerer Josef , Lembeck Fred 
Published: July 2012

Plasma adrenocorticotrophic hormone (ACTH) concentrations were measured in rats following exposure to anaesthetic agents, after stimulation of peripheral sensory nerves, and during psychological stress.
In rats, kept in their home cages, the i.p. injection of sodium pentobarbitone did not cause an increase in plasma ACTH, whereas injection of urethane increased plasma ACTH several times. In rats transferred to a glass dessicator and inhaling oxygen, plasma ACTH was more than 3 fold higher than in rats in their home cage. Exposure to nitrous oxide, halothane or ether in a glass dessicator produced significantly higher plasma ACTH concentrations when compared to exposure in the home cage.
In rats anaesthetized with pentobarbitone, the electrical stimulation of large myelinated afferents in the sciatic nerve did not trigger a measurable increase in ACTH secretion, whereas stimulation of afferent Aδ‐ and C‐fibres significantly elevated plasma ACTH concentrations. Rats treated as neonates with capsaicin showed an attenuated ACTH response to A and C‐fibre stimulation.
Similarly, capsaicin pretreatment reduced the increase in ACTH secretion during morphine withdrawal; a similar effect was produced by clonidine.
ACTH secretion following open field exposure, ether stress or hypoglycaemia was not changed by capsaicin pretreatment.
It was concluded that capsaicin‐sensitive afferents are involved in the secretion of ACTH elicited by somatosensory forms of stress. Centrally evoked ACTH release is not affected by capsaicin pretreatment.
Immediate anaphylactic bronchoconstriction induces airway hyperreactivity in anaesthetized guinea‐pigs
Authors: Daffonchio Luisa , Payne Adrian N. , Lees Ian W. , Whittle Brendan J.R. 
Published: July 2012

The possible acute occurrence of airway hyperreactivity after immediate‐type bronchial anaphylaxis has been investigated in anaesthetized guinea‐pigs actively sensitized to ovalbumin (OA).Aerosol challenge (OA 10 mg ml−1, 5s) provoked immediate bronchoconstriction which was substantially, although incompletely, reversed by isoprenaline (Iso) infusion (1 μg kg−1min−1) for 10 min).Bronchoconstrictor responses to 5‐hydroxytryptamine (5‐HT) were enhanced in challenged animals when compared to those in non‐challenged animals that had also received Iso. This was seen as a leftward shift in the location of the dose‐response curve for the bronchoconstrictor effect of 5‐HT (dose‐ratio 2.45, 95% confidence limits 1.77–3.38;P< 0.01). This phenomenon was associated with pulmonary infiltration of polymorphonuclear leukocytes, which was not modified by Iso treatment.Iso infusion alone caused a slight enhancement of airway reactivity seen as a small leftward shift of the dose‐response curve for the bronchoconstrictor effect of 5‐HT (dose‐ratio 1.51, 95% confidence limits 1.07–2.13;P< 0.05).These results support a causal relationship between acute pulmonary inflammation and airway hyperreactivity in an animal model of human allergic asthma.
The influence of activation or inhibition of protein kinase C on the release of radioactivity from rat isolated atria labelled with [3H]‐noradrenaline
Authors: Ishac Edward J.N. , de Luca Anthony 
Published: July 2012

The release of radioactivity from rat isolated atria preloaded with [3H]‐noradrenaline ([3H]‐NA) evoked by electrical field stimulation (2Hz, 1 ms, 60s) of intraneuronal sympathetic nerves, high potassium (64.7 mm) or tyramine (0.3μm) was used as an index of noradrenaline release.
Activation of protein kinase C by phorbol 12‐myristate 13‐acetate (PMA) produced a concentration‐dependent enhancement of field stimulation‐induced outflow of radioactivity, whereas polymyxin B, an inhibitor of protein kinase C, reduced [3H]‐NA release evoked by field stimulation. The enhancement observed in the presence of PMA was attenuated by polymyxin B (10 and 70 μm).
Release of noradrenaline evoked by membrane depolarization in a high potassium medium was similarly affected by PMA and polymyxin B.
In contrast, the release of noradrenaline evoked by the indirectly acting sympathomimetic amine, tyramine, was not altered by PMA. Polymyxin B in a concentration of 70 μm, but not 10 μm caused a slight reduction in tyramine‐induced outflow of radioactivity.
The spontaneous outflow of radioactive compounds was not affected by either PMA or polymyxin B in the bathing medium.
The findings suggest that protein kinase C may play a role in the exocytotic release of noradrenaline but not in the displacement of noradrenaline by indirectly acting sympathomimetic amines.
Effects of leukotriene D4 on the mechanical and electrical properties of guinea‐pig isolated trachealis
Authors: McCaig Dorothy J. , Rodger I. W. 
Published: July 2012

The effects of leukotriene D4 (LTD4) on mechanical and electrical activity were examined in guinea‐pig isolated trachealis muscle and compared with two other bronchoconstrictors, methacholine and potassium chloride (KCl).
LTD4 elicited concentration‐dependent increases in tension in trachealis muscle which were slower in time course than responses induced by either methacholine or KCl. The maximum response to LTD4 was approximately 85% of the methacholine maximum.
At a concentration close to the EC50 for tension changes, LTD4 had no significant effect oneither transmembrane potential or slow wave activity recorded in single trachealis cells.
At a concentration close to the EC90 for tension changes, LTD4 caused significant membrane depolarization, transiently reduced the amplitude and increased the frequency of slow wave discharge and ultimately abolished slow wave discharge. LTD4‐induced depolarization was less marked, and developed more slowly, than that evoked by either methacholine or KCl.
These results show that LTD4 can elicit substantial increases in tension without altering transmembrane potential and are consistent with the view that LTD4 initiates contraction mainly through potential‐independent mechanisms. However, at high concentrations the depolarization evoked by LTD4 allows the possibility that potential‐dependent mechanisms may contribute to the spasm.
Flushing and haemodynamic responses to vasopressin peptides in the rhesus monkey
Authors: Brooks David P. , Koster Paul F. , Stassen Frans L. , Albrightson Christine R. , Huffman William F. , Wasserman Martin A. , Kinter Lewis B. 
Published: July 2012

The mechanism of the flushing, hypotension and tachycardia associated with i.v. administration of desGlyd(CH2)5D‐Tyr(Et)VAVP (SK&F 101926; 25 μg kg−1) and the selective V2 antidiuretic agonist, desamino‐8‐D‐arginine vasopressin (dDAVP; 3 μg kg−1) was studied in ketamine‐anaesthetized rhesus monkeys.
The flushing associated with SK&F 101926 was reduced by pretreatment with a mast cell stabilizer and by repeated administration of peptide (within 2–4 weeks). A similar desensitization to dDAVP‐associated flushing was observed on repeated administration.
Treatment with dDAVP also resulted in reduced SK&F 101926‐associated flushing.
The hypotension associated with SK&F 101926 was not affected by pretreatment with a mast cell stabilizer. A similar degree of hypotension was observed with repeated administration of either SK&F 101926 or dDAVP.
The tachycardia associated with SK&F 101926 was reduced by pretreatment with a mast cell stabilizer or repeated administration of SK&F 101926. Repeated administration of dDAVP, however, resulted in an enhanced tachycardia.
Indomethacin (5 mg kg−1 i.v.) did not alter the flushing or the hypotension associated with the administration of either SK&F 101926 or dDAVP, but resulted in an enhanced tachycardia to SK&F 101926.
Administration of a selective V1 vasopressor antagonist did not result in flushing, hypotension or tachycardia.
It was concluded that the flushing response to vasopressin‐like peptides in rhesus monkeys may be due to an action on mast cells, whereas the haemodynamic responses are not, but probably involve direct vasodilator actions.
Early induction by crotoxin of biphasic frequency changes and giant miniature endplate potentials in frog muscle
Authors: Hawgood Barbara J. , Smith I. Christopher H. , Strong Peter N. 
Published: July 2012

Following the addition of crotoxin (250 nm) at the frog neuromuscular junction, there was an initial fall in frequency of miniature endplate potentials (m.e.p.ps), followed by a secondary rise which was characterized by the appearance of large spontaneous potentials (giants, g.m.e.p.ps) and an occasional large potential of the burst type.
In the presence of 2‐(4‐phenylpiperidino)cyclohexanol (AH5183, vesicamol), an inhibitor of vesicular acetylcholine uptake, the frequency of g.m.e.p.ps induced by crotoxin was reduced.
The characteristic changes in m.e.p.p. frequency and amplitude distribution were absent with crotoxin in Sr‐EGTA Ringer. In the presence of high concentrations of Mn (3.6 or 5.4 mM with 0.9 mM Ca), the crotoxin‐induced initial fall and the onset of the secondary rise in m.e.p.p. and g.m.e.p.p. frequencies were slower. The timing of these phases was unaffected by Ca concentrations ranging from 6.3 to 0.9 mM.
High concentrations of Mn ions partially inhibited the phospholipase A2 activity of crotoxin on artificial phospholipid membranes. This also supports the involvement of the Ca‐dependent phospholipase A2 subunit in both phases of the physiological action of the toxin.
G.m.e.p.ps were associated with a moderate increase in m.e.p.p. frequency (2–3 s−1) and were of a time‐course similar to that of m.e.p.ps. They persisted after washing with medium lacking Ca ions and in the presence of Ca‐Mn Ringer that blocked evoked responses.
It is concluded that crotoxin, acting through its phospholipase A2 subunit, produces specific disturbances of synaptic exocytosis and vesicle formation in the axolemma of the motor nerve terminal which lead to biphasic changes in m.e.p.p. frequency and the onset of large spontaneous potentials.
Effects of clonidine and yohimbine on a C‐fibre‐evoked blood pressure reflex in the rat
Authors: Donnerer Josef , Yan Zhao , Lembeck Fred 
Published: July 2012

The involvement of α2‐adrenoceptors in a capsaicin‐induced depressor reflex in the rat has been investigated.
The reflex fall in blood pressure following an intra‐arterial injection of capsaicin was partially blocked by an intrathecal infusion of clonidine (1 μg) at the spinal cord level L4‐L5, an effect which was abolished by the prior intrathecal infusion of yohimbine (5 μg).
Clonidine (1μg) given intracisternally blocked the depressor reflex almost completely; however, it also produced a gradual, prolonged fall in mean carotid pressure.
Yohimbine (20 μg) given intracisternally did not change mean blood pressure but had a dual effect on the depressor reflex in response to the capsaicin injection: a short period of enhanced reflex response was followed by a long lasting inhibition of the response.
It was concluded that α2‐adrenoceptors in the spinal cord inhibit the capsaicin‐evoked depressor reflex and that pre‐ and postsynaptic α2‐adrenoceptors in the brain stem modulate this reflex.
Perinatal lead exposure alters the development of δ‐but not μ‐opioid receptors in rat brain
Authors: McDowell Julia , Kitchen Ian 
Published: July 2012

Low level lead exposure has been shown to impair the development of opioid peptide levels in the brain, and to impair antinociceptive responses to opioid drugs. We have now studied the effects of lead exposure on the development of opioid receptors using ligand binding studies.
The ontogenesis of μ‐ and δ‐opioid binding sites was studied using rat whole brain membranes and [3H]‐[D‐Ala2MePhe4‐Gly‐ol]enkephalin and [3H]‐[D‐Pen2,D‐Pen5]enkephalin as binding ligands. Rats were exposed to lead during development by addition of lead acetate (at 100–1000 p.p.m.) to the maternal drinking water from conception to postnatal day 14.
Perinatal lead exposure had no significant effects on the binding affinity (KD) or binding capacity (Bmax) for the μ‐opioid receptor measured at postnatal days 10, 21 and 30. Lead exposure (at 1000 p.p.m.) increased the KD for the δ‐opioid receptor at postnatal days 15, 21, 35 and 50 but had no effect on the binding capacity. No indications of overt toxicity were observed and blood lead levels were in the ranges considered to represent subclinical lead toxicity in man.
The lack of effect of lead on μ‐receptor binding contrasts with previously described impairment of antinociceptive effects of μ‐agonists suggesting that the toxicity is not manifested at the μ‐binding site. However, the δ‐opioid receptor appears to be more sensitive to lead exposure and the persistent changes in δ‐site affinity after cessation of lead exposure suggest irreversible damage in the production of the receptor protein.
Effect of soluble factors from nerve and muscle on α‐bungarotoxin binding sites in isolated sarcolemmal membranes of the rat
Authors: Harborne Alan J. , Smith Margaret E. 
Published: July 2012

Sarcolemmal membranes were isolated from normal and from denervated muscles and the specific binding of [125I]‐α‐bungarotoxin to the membranes was determined.
Cytosol prepared from either slow (soleus) or fast (extensor digitorum longus) muscle increased the toxin binding. Similar effects were seen with cytosol from muscles which had been denervated 5 to 7 days previously and with cytosol from sciatic nerve. A purified preparation of a bacterial phospholipase C also produced this effect.
Bathing medium in which normal or denervated muscles had been incubated, increased the toxin binding to normal membranes, but the normal bathing medium decreased the binding to membranes prepared from denervated muscles.
The possibility that pre‐existing latent acetylcholine receptors can be activated by intracellular factors released from muscles is discussed.
Bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs
Authors: Sassen L.M.A. , den Boer M.O. , Rensen R.J. , Saxena P.R. , Verdouw P.D. 
Published: July 2012

The ability of the cardioselective β‐adrenoceptor antagonist bisoprolol ((±)−1‐[4‐(2‐isopropoxyethoxymethyl)‐phenoxy]‐3‐isopropyl‐amino‐2‐propanol hemifumarate, EMD 33512) to suppress isoprenaline‐induced increases in heart rate and maximal rate of rise in left ventricular pressure (LVdP/dtmax) was studied in 6 anaesthetized pigs given 4 cumulative doses (16, 64, 256 and 1024 μg kg−1). Bisoprolol was about 2 times more effective in suppressing isoprenaline‐induced increases in LVdP/dtmax than those in heart rate.
In 8 animals which had a partial stenosis of the left anterior descending coronary artery (LADCA), the effects of 3 consecutive doses (50, 200 and 750 μg kg−1) of bisoprolol were studied on systemic haemodynamics, regional myocardial perfusion and function. The effects of the drug were compared with those obtained in a group of 9 animals with LADCA stenosis which did not receive any treatment.
The lowest dose of bisoprolol (50 μg kg−1) increased perfusion of the ischaemic myocardium (which had been reduced from 123 ± 20 ml min−1 100 g−1 to 42 ± 11 ml min−1 100 g−1) by 21 ± 10 ml min−1 100 g−1 (P < 0.05). In particular the subendocardial layers, which were most severely affected by the stenosis (a decrease from 128 ± 19 ml min−1 100 g−1 to 20 ± 6 ml min−1 100 g−1) benefited from the administration of the drug (an increase of 30 ± 10 ml min−1 100 g−1). Perfusion of the subepicardium was not significantly affected. With the higher dose only a minor additional improvement in perfusion of the ischaemic myocardium was observed.
The negative chronotropic response is the most likely factor leading to the improvement in perfusion.
Myocardial wall thickening, which decreased from 41 ± 2% to 9 ± 4% (P < 0.05) due to the hypoperfusion, did not improve after administration of the drug. This lack of improvement may possibly be due to the duration of ischaemia before and the magnitude of the flow deficit after bisoprolol administration.
Between 15 and 60 min of ischaemia, 5 of the 9 untreated animals had an episode of ventricular fibrillation compared with only 1 of the 8 animals treated with bisoprolol, in spite of an initially larger flow reduction in the treated animals. The more homogeneous flow distribution after bisoprolol might account for the lower incidence of arrhythmias in this group.
It was demonstrated that bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs even at doses (50 μg kg−1) that only moderately antagonize isoprenaline‐induced cardiostimulatory effects.