bluuebunny/crossref_metadata_2025_split huggingface dataset:
The combined electrophysiological effects of lignocaine and sotalol in canine isolated cardiac Purkinje fibres are rate‐dependent
Authors: Lathrop David A. , Varró András 
Published: July 2012

The frequency‐dependent electrophysiological effects of lignocaine, sotalol, and their combination were studied in dog isolated cardiac Purkinje fibres, both at various constant rates of stimulation and following abrupt changes in pacing cycle length.
The combined effect of 18 μm lignocaine and 30 μm sotalol selectively lengthened duration of premature action potentials evoked at a diastolic interval of 40 ms (from 172.2 ± 5.4 to 201.7 ± 4.9 ms, n = 6, P > 0.01) without significantly changing the durations of action potentials evoked at the basic cycle length of 500 ms (259.1 ± 7.7 vs 251.9 ± 3.9 ms, n = 11).
The combination of lignocaine with sotalol, like lignocaine alone, displayed a use‐dependent depression of and revealed a slow component for a recovery of (τ = 173.5 ± 16.0 ms, n = 5).
The kinetics for restitution of action potential duration were also slowed by the combination of the two dwo drugs (τf = 173.6 ± 16.7, before, vs 268.5 ± 8.5 ms, after; n = 5, P > 0.01), while the maximum action potential duration attained in this relation was not increased as it was by sotalol alone.
Lignocaine, therefore, appeared to inhibit the sotalol‐induced lengthening of action potential duration at slow pacing rates and at long diastolic intervals. The combination of lignocaine with sotalol also completely abolished the occurrence of sotalol‐induced early afterdepolarizations.
Finally, sotalol alone moderately increased the range of premature action potential durations, while the combination of the two drugs significantly decreased this parameter.
These findings indicate that the combination of lignocaine with sotalol may provide important, and unique, beneficial electrophysiological alterations that might be expected to provide enhanced antiarrhythmic efficacy in patients.
Dual effects of capsaicin on responses of the rabbit ear artery to field stimulation
Authors: Moritoki Hideki , Takase Hideshi , Tanioka Asao 
Published: July 2012

The effects of capsaicin (Cap) on contractions of ring segments of rabbit ear artery induced by field stimulation were studied.
At low concentrations (0.3–3 μm) Cap caused transient enhancement and at higher concentrations (above 3 μm) inhibition of stimulation‐induced contractions, without affecting noradrenaline (NA)‐induced contractions.
In the continuous presence of high concentrations of Cap, rebound facilitation was observed after inhibition, and at this stage, Cap elicited less inhibition of the response.
Repeated application of Cap at 60 min intervals irreversibly desensitized the artery to the inhibitory effect of Cap.
Functional removal of the endothelium enhanced the facilitatory effect of low concentrations of Cap and attenuated its inhibitory effect.
Pretreatment with indomethacin abolished the facilitatory effect of Cap and enhanced its inhibitory effect, indicating that prostaglandins are involved in the action of Cap. The effect of indomethacin was more marked in preparations from which the endothelium had been removed.
Desensitization to substance P (SP) or substance K (SK), did not affect either the inhibitory or the facilitatory effect of Cap.
These results suggest that the dual effects of Cap on stimulation‐induced contractions of rabbit ear artery may arise from the release of multiple mediators that act prejunctionally to modulate NA release. The stimulant effect seems to be mediated by prostanoids, while the inhibitory effect seems to be caused by a substance(s) that is not SP or SK. The possibility that the mediator is calcitonin gene‐related peptide requires further study.
Effect of the nootropic drug oxiracetam on field potentials of rat hippocampal slices
Authors: Pugliese Anna Maria , Corradetti Renato , Ballerini Laura , Pepeu Giancarlo 
Published: July 2012

The effect of the nootropic drug oxiracetam on hippocampal neurotransmission was investigated in the CA1 region of the rat hippocampal slice in vitro by use of extracellular recordings.
Superfusion of oxiracetam (0.1–100 μm) produced a concentration‐dependent, wash‐resistant (>90 min), increase in initial slope and amplitude of the dendritic field excitatory postsynaptic potential (e.p.s.p.). This increase was maximal at a concentration of 1 μm (70%).
Input‐output curves relating the initial slope to the amplitude of the afferent volley were significantly (P < 0.05) steeper and showed a greater maximal response in the presence of 1 μm oxiracetam than in control conditions.
Two trains of high frequency stimulation (100 Hz, 0.4 s, 5 min apart) delivered in the stratum radiatum 30 min after washout of oxiracetam (1 μm) still elicited a long‐term potentiation (LTP) of the field e.p.s.p. However, the absolute magnitude of the LTP produced did not differ from that obtained in untreated slices.
After induction and establishment of LTP, oxiracetam (1 μm) had a smaller (27%) and reversible effect on the evoked field e.p.s.p.
d‐2‐Amino‐5‐phosphonopentanoic acid (AP‐5), at the same concentration (50 μm) which in our conditions prevented the induction of LTP, blocked the action of 1 μm oxiracetam and strongly depressed the effect of higher concentrations of the nootropic drug.
It is concluded that oxiracetam provokes an enduring increase of neurotransmission in the CA1 rat hippocampal region. This action appears to share some features with LTP as indicated by its persistence, sensitivity to AP‐5 and lack of additivity with electrically‐induced LTP.
The effects of pyrogallol and hydroquinone on the response to NANC nerve stimulation in the rat anococcygeus and the bovine retractor penis muscles
Authors: Gillespie John S. , Sheng Hong 
Published: July 2012

The effects of pyrogallol and hydroquinone on the bovine retractor penis (BRP) and rat anococcygeus muscles to non‐adrenergic, non‐cholinergic (NANC) nerve stimulation have been examined. Both drugs at a concentration of 10−4 m significantly reduced the response in the rat anococcygeus muscle but had no effect in the BRP muscle.
The inhibition of the NANC response in the rat anococcygeus muscle by pyrogallol was completely reversed by superoxide dismutase suggesting it was due to the generation of superoxide anions.
Pyrogallol inhibited the response to nitric oxide (NO) in the rat anococcygeus muscle but not that to 3‐isobutyl‐1‐methyl‐xanthine (IBMX) which confirmed a selective action.
These results suggest that the NANC neurotransmitter in the rat anococcygeus muscle is susceptible to superoxide anions and may be NO or a substance that can liberate NO.
Caffeine acting on pregnant rat myometrium: analysis of its relaxant action and its failure to release Ca2+ from intracellular stores
Authors: Savineau Jean‐Pierre , Mironneau Jean 
Published: July 2012

The effect of caffeine on mechanical activity was studied in pregnant rat myometrium.
In muscle cells with intact plasmalemmae, caffeine (0.1–50 mm) produced no contraction whatever the experimental conditions.
Caffeine (0.1–10 mm) inhibited, in a concentration‐dependent manner, contractions induced by electrical stimulation, potassium‐rich (60 mm K+) solution, sodium‐free solution or oxytocin (22.5 nm).
In Ca2+‐free solution, various substances (oxytocin, sodium orthovanadate and prostaglandin E2) evoked sustained contractions that were suppressed by caffeine (5–10 mm). When caffeine (> 5 mm) was applied during Ca2+‐loading of the tissue (2.1 mm Ca2+, 5 min) in the presence of a K+‐rich solution, the subsequent transient contraction induced by a short application (10 s) of oxytocin (22.5 nm) in Ca‐free solution was reduced (63 ± 3.5% reduction for 20 mm caffeine, n = 4).
In saponin‐skinned strips, application of caffeine (5–10 mm) during loading of the Ca2+‐store increased the subsequent contraction induced by myo‐inositol 1,4,5 trisphosphate (IP3, 10 μm). Caffeine (10–30 mm) decreased calcium‐activated contractions in skinned fibres lacking a functional internal Ca‐store. This effect was reduced by the cyclic AMP‐dependent protein kinase inhibitor Thr‐Thr‐Tyr‐Ala‐Asp‐Phe‐Ile‐Ala‐Ser‐Gly‐Arg‐Thr‐Gly‐Arg‐Arg‐Asn‐Ala‐Ile‐His‐Asp (8 μm).
In conclusion, it is suggested that the inability of caffeine to cause spasm of rat myometrium is due to the absence of a caffeine‐sensitive calcium‐release channel in the sarcoplasmic reticulum. Relaxant effects of caffeine can be explained by mechanisms leading to a decrease in both the cytoplasmic free Ca2+ concentration and the Ca2+‐sensitivity of the contractile machinery.
Characterisation of stereospecific binding sites for inositol 1,4,5‐trisphosphate in airway smooth muscle
Authors: Chilvers E.R. , Challiss R.A.J. , Willcocks A.L. , Potter B.V.L. , Barnes P.J. , Nahorski S.R. 
Published: July 2012

A ‘P2’ membrane fraction of bovine tracheal smooth muscle displays high affinity (KD 3.8 ± 0.2 nm), saturable (Bmax 1003 ± 170 fmol mg−1 protein) and reversible binding of d‐myo[3H]‐inositol 1,4,5‐trisphosphate ([3H]‐Ins(1,4,5)P3).
This binding site shows strict stereo‐ and positional specificity for the d‐Ins(1,4,5)P3 isomer with l‐Ins(1,4,5)P3, dl‐Ins(1,3,4,5)P4 and d‐Ins(1,3,4)P3 displacing [3H]‐Ins(1,4,5)P3 with Ki values of 20 μm, 0.35 μm and 2.4 μm, respectively.
Specific binding of [3H]‐Ins(1,4,5)P3 is enhanced at alkaline pH values (maximal at pH 7.75) and, in distinct contrast to [3H]‐Ins(1,4,5)P3 binding in rat cerebellum membranes, is not inhibited by Ca2+ (5–500 μm).
Heparin displaces [3H]‐Ins(1,4,5)P3 specific binding with an IC50 of 7.6 ± 1.0 μg ml−1.
Comparative studies demonstrated specific [3H]‐Ins(1,4,5)P3 binding in bovine cardiac atrial preparations (Bmax 75 ± 5 fmol mg−1 protein) and very low specific [3H]‐Ins(1,4,5)P3 binding in bovine cardiac ventricle and skeletal muscle membranes (≤ 25 fmol mg−1 protein).
The action of atriopeptin III on renal function in two models of chronic renal failure in the rat
Authors: Johns Edward J. , Rutkowski Bolesław 
Published: July 2012

The natriuretic and diuretic effects of atriopeptin III (125, 250 and 500 ng kg−1, i.v.) were studied in groups of rats anaesthetized with pentobarbitone which were either sham controls, unilaterally nephrectomized controls, adenine‐fed or subtotal nephrectomy chronic renal failure models.
Atriopeptin III given at these doses to the sham control animals had no effect on blood pressure, renal blood flow or glomerular filtration rate but reversibly increased urine flow, between 46% to 54%, absolute sodium excretion, between 52% to 61%, and fractional sodium excretion, between 48% to 54% (all P values <0.05) from the lowest to the highest dose. The adenine‐fed chronic renal failure group of rats had a reduced renal blood flow of between 30 and 75%, and glomerular filtration rate of approximately 20%, compared to the sham controls. Administration of atriopeptin at 125, 250 and 500 ng kg−1 to the animals with renal failure increased water and sodium excretion to the same degree as observed in the sham group of rats.
In the group of unilaterally nephrectomized rats, atriopeptin III, at 125, 250 and 500 ng kg−1 increased urine flow by 36%, 47% and 72%, respectively, absolute sodium excretion by 37%, 57% and 106%, respectively, and fractional sodium excretion by 46%, 45% and 102%, respectively. A similar pattern of responses was observed in the subtotal nephrectomy, chronic renal failure group in which filtration rate was approximately 4 times less than the controls. Although the magnitude of the urine flow and absolute sodium excretion responses were the same, the increases in fractional sodium excretion were all significantly larger than in the unilaterally nephrectomized control group.
These results show that in two different models of chronic renal failure, atriopeptin III still caused a natriuresis and diuresis. This suggests that the nephrons retain sensitivity to the atrial natriuretic peptides in diseases such as chronic renal failure and that these compounds may be useful in mobilizing body fluids in this situation.
The role of the endothelium in mediating the actions of ATP, adenosine and acetylcholine on flow through blood vessels in the rabbit knee joint
Authors: Ferrell W.R. , Khoshbaten A. 
Published: July 2012

An in vitro preparation of the rabbit knee joint, perfused with oxygenated Locke solution, was used to investigate the presence of purinoceptors and the role of endothelium within articular blood vessels.
The basal tone of the blood vessels was not affected by adenosine or acetylcholine. Adenosine 5′‐triphosphate (ATP) injection produced vasoconstriction which was unaffected by removal of the endothelial layer, but diminished by α, beta methylene ATP, a compound which desensitizes P2‐purinoceptors.
When knee joint blood vessel tone was raised by perfusion with vasopressin (10−8m) or 5‐hydroxytryptamine (10−5 m), acetylcholine, ATP and adenosine were all found to induce concentration‐dependent relaxation of these vessels. ATP was found to have a dual effect of transient constriction followed by longer‐lasting dilatation.
3‐Methylxanthine, a P1‐purinoceptor antagonist significantly reduced the relaxation response to adenosine but had no effect on the vasodilator effect of ATP.
Removal of the endothelial layer virtually abolished the vasodilator effects of acetylcholine and ATP but not adenosine.
These results demonstrate that articular blood vessels supplying the rabbit knee contain P1‐purinoceptors located on the vascular smooth muscle which mediate vasodilatation. P2‐purinoceptors mediating a constrictor effect are also present on this smooth muscle. It is likely that the vasodilator effect of ATP is mediated via P2‐purinoceptors located on the endothelial layer.
Specific but differential antagonism by glibenclamide of the vasodepressor effects of cromakalim and nicorandil in spinally‐anaesthetized dogs
Authors: Yamada Hiroaki , Yoneyama Fumiya , Satoh Keisuke , Taira Norio 
Published: July 2012

Whether the vasodepressor effects of cromakalim and nicorandil, potassium channel openers, were differentially antagonized by glibenclamide, a supposed specific antagonist of potassium channel openers, was investigated in spinally‐anaesthetized dogs in which arterial pressure was maintained elevated by i.v. infusion of noradrenaline.
Cumulative administration of cromakalim (3–100 μg kg−1, i.v.), nicorandil (30–1000 μg kg−1, i.v.), diltiazem (3–300 μg kg−1, i.v.) and nitroglycerin (0.3–100 μg kg−1, i.v.) caused dose‐dependent decreases in mean arterial pressure. In dogs which received glibenclamide (3 mg kg−1, i.v.), the dose‐vasodepressor response curves for cromakalim and nicorandil were located on the right in parallel to the respective curves determined in control dogs, but those for diltiazem and nitroglycerin were not different. ED50% values increased about 6.7 fold for cromakalim and 2.2 fold for nicorandil.
The depression of LV dP/dtmax produced by a high dose of cromakalim (100 μg kg−1 i.v.) was abolished by glibenclamide and that produced by nicorandil was not only antagonized but converted to an increase.
These results suggest that the vasodepressor action of cromakalim is due predominantly to potassium channel opening, but that of nicorandil involves not only potassium channel opening but its action as a nitrate.
Tachykinins activate guinea‐pig alveolar macrophages: involvement of NK2 and NK1 receptors
Authors: Brunelleschi Sandra , Vanni Lucia , Ledda Fabrizio , Giotti Alberto , Maggi Carlo Alberto , Fantozzi Roberto 
Published: July 2012

The effects of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were evaluated on superoxide anion () production by guinea‐pig alveolar macrophages (AM).
SP dose‐dependently (ED50 = 0.7 nm) evoked production from guinea‐pig AM; the N‐terminal heptapeptide, SP(1–7), was ineffective. In the presence of thiorphan (10−5 m), an enkephalinase inhibitor, the stimulating effects of SP were not significantly modified. NKA and NKB were both able to induce production from guinea‐pig AM, ED50 values being 0.1 and 1.3 nm, respectively. Therefore, the rank order of activity of natural tachykinins was NKA > SP > NKB. Tachykinin‐evoked effects were quantitatively similar to those elicited by the autacoid mediator PAF‐acether and less than those induced by the synthetic peptide N‐formylmethionyl‐leucyl‐phenylalanine (FMLP).
The NK2 receptor agonist [β‐Ala8]‐NKA (4–10) dose‐dependently evoked production from guinea‐pig AM; the NK1 receptor agonist [Pro9]‐SP sulphone acted only at high concentrations, while the NK3 receptor agonist [Me, Phe7]‐NKB was ineffective.
These findings indicate that guinea‐pig AM possess NK2 and possibly some NK1 tachykinin receptors and further suggest tachykinin involvement in lung pathophysiology.
Caffeine‐induced behavioural stimulation is dose‐ and concentration‐dependent
Authors: Kaplan Gary B. , Tai Nhan T. , Greenblatt David J. , Shader Richard I. 
Published: July 2012

The relationship between plasma and brain caffeine and metabolite concentrations and behavioural stimulation was investigated over a 4 h time course.
CD‐1 mice receiving single intraperitoneal doses of caffeine‐sodium benzoate solution (caffeine doses: 0, 20, and 40 mg kg−1) were evaluated in an activity monitor, and their plasma and brain caffeine and metabolite concentrations were determined by high performance liquid chromatography (h.p.l.c.).
Kinetic variables for caffeine at low and high caffeine doses were: volume of distribution (Vd), 1.16 and 0.881 kg−1; plasma elimination half‐life (t1/2), 1.25 and 1.62 h; brain t1/2, 0.93 and 1.30h; clearance, 0.64 and 0.381 h−1 kg−1, respectively, with Vd and brain t1/2 differing significantly between the two caffeine doses.
Low‐dose caffeine stimulated vertical behaviours significantly more than high‐dose, during the first 150 min post‐dosage; both doses stimulated vertical behaviours significantly more than vehicle treatment.
Low‐dose and high‐dose caffeine stimulated horizontal and stereotypic behaviours equivalently, during the first 150 min post‐dosage; both doses stimulated these behaviours significantly more than vehicle.
Only later, 150 min post‐dosage, did high‐dose caffeine stimulate all behaviours significantly more than both low‐dose and vehicle treatment; this occurred when caffeine concentrations had fallen to approximately 10 μg g−1 in the high‐dose group.
The maximal stimulant effects of caffeine occurred in an intermediate concentration range, between 10–20 μg g−1, while lower and higher concentrations produced either no additional stimulation or decrements in activity.
Cationic factors affecting phospholipase activities from human lung
Authors: Yeats D.A. , Bakhle Y.S. 
Published: July 2012

The effects of varying H+ and other cation concentrations on phospholipase activity were investigated on two particulate fractions from human lung, corresponding to the mitochondrial and microsomal fractions.
Three 14C‐labelled substrates, arachidonyl‐phosphatidylcholine (PC), ‐phosphatidylethanolamine (PE) and ‐phosphatidylinositol (PI) were used.
For two substrates, PE and PI, hydrolysis was maximal at pH 6, with either subcellular fraction.
Hydrolysis of all three substrates was strongly inhibited by EDTA and EGTA (10–25 mm). Addition of 2,2‐dipyridyl, o‐phenanthroline, 8‐hydroxyquinoline or desferrioxamine (10 μm‐1 mm) did not inhibit but often increased hydrolysis of all substrates.
Addition of Zn2+, as ZnCl2, (10 μm‐1 mm) inhibited PE and PI, but not PC, hydrolysis.
The phospholipase activities from human lung appear to be dependent on Ca2+ for maximal activity and to be inhibited by other metal ions including Zn2+.
The effects of granisetron, ICS 205–930 and ondansetron on the visceral pain reflex induced by duodenal distension
Authors: Moss Helen E. , Sanger Gareth J. 
Published: July 2012

Distension of the duodenum in anaesthetized rats, by rapid application of intraluminal pressures (10–75 cmH2O), evoked falls in diastolic blood pressure and intragastric pressure.
The distension‐induced responses were blocked by pretreatment with morphine (20 mg kg−1, s.c.), an action reversible by injection of naloxone (5 mg kg−1, i.v.).
Bilateral cervical vagotomy reduced the distension‐evoked fall in intragastric pressure but had no effect on the corresponding fall in blood pressure.
Granisetron or ICS 205–930 (1–1000 μg kg−1, i.v.) had no effects on duodenal intraluminal pressure, but reduced the responses to distension with a bell‐shaped dose‐response relationship. Ondansetron (1–1000 μg kg−1, i.v.) did not reduce the reflex responses.
These results show that the 5‐HT3 receptor antagonists used exerted different effects on the reflex responses to duodenal distension.
Effects of tetraethylammonium and 4‐aminopyridine on outward currents and excitability in canine tracheal smooth muscle cells
Authors: Muraki K. , Imaizumi Y. , Kojima T. , Kawai T. , Watanabe M. 
Published: July 2012

The effects of tetraethylammonium (TEA) and 4‐aminopyridine (4‐AP) on membrane currents and on single channel K currents in smooth muscle cells isolated from canine trachea were examined by use of tight seal whole cell‐ and patch‐clamp techniques.
Depolarizing current applied through a recording pipette did not elicit an action potential under current clamp. A strong outward rectification was observed.
In most cells under voltage‐clamp, only an outward current was observed upon depolarization from −60 mV when a pipette solution contained mainly KCl. The outward current consisted of three components; a large initial transient, a following sustained component and an additional component of irregular small transients on the sustained one. The two transient components were almost abolished when extracellular and pipette solutions contained 2.2 mm Cd2+ (0 mm Ca2+) and 10 mm EGTA, respectively. The sustained component was well maintained under these conditions.
TEA at low concentrations (<1 mm) effectively decreased the transient components and made the outward current smooth; it also suppressed the sustained component at higher concentrations. In outside‐out patches, external 1 mm TEA reduced the single channel conductance of Ca‐activated K channels by about 87% whereas 3 mm 4‐AP did not. 4‐AP at low concentrations (<3 mm) selectively reduced the sustained component of the outward current.
A Ca current recorded after the suppression of outward current by internal Cs+ had a peak of approximately 200 pA at + 10 mV (holding potential: −60 mV). The half inactivation voltage in the steady‐state was approximately −30 mV.
Simultaneous application of 1 mm TEA and 4‐AP reduced the outward current and unmasked a Ca current. Under these conditions, an action potential with overshoot was easily elicited under current clamp.
It is concluded that the low excitability of canine tracheal smooth muscle cell upon depolarization is due to a large outward K current which consists of Ca‐dependent and Ca‐independent components. The peak amplitude of the Ca current is similar to that in highly excitable smooth muscle cells such as those of the ureter.