bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potassium induces relaxation and hyperpolarization of circular muscles but contraction of longitudinal muscles of pig duodenum
Authors: Kimura I. , Kimura M. , Kimura M. 
Published: July 2012

The mechanisms by which K+ relaxes circular muscles of pig duodenum were investigated, and compared with the response of the longitudinal muscles to K+.
Circular muscles were concentration‐dependently relaxed by 8.3–23.6 mm K+, but contracted by 47.2–143.4 mmK+.
Longitudinal muscles were contracted by 11.8–94.4 mm.K+.
The relaxation of circular muscles was correlated with hyperpolarization (4 mV), but evoked Ca2+ spikes were not suppressed.
Neither ouabain (0.14 μm) nor phentolamine (10 μm) blocked the relaxation, but tetrodotoxin (TTX, 0.63 μm) blocked both the relaxation and hyperpolarization. Mesaconitine (0.16 μm) increased the relaxation. Inhibitory junction potentials and concomitant relaxations were also blocked by TTX.
The results suggest that K+‐induced relaxation is caused by the release of a non‐adrenergic inhibitory transmitter.
Inhibition of GABA uptake potentiates the conductance increase produced by GABA‐mimetic compounds on single neurones in isolated olfactory cortex slices of the guinea‐pig
Authors: Brown D.A. , Scholfield C.N. 
Published: July 2012

Membrane potential and input conductance were recorded in single neurones in slices of guinea‐pig olfactory cortex in vitro. γ‐Aminobutyric acid (GABA) and GABA‐mimetic compounds were applied by bath‐perfusion. Potency was measured as the concentration required to double the input conductance.
The potency of GABA was increased (i.e. the equi‐effective concentrations were reduced) by 15.5 ± 2.3 times (mean ± s.e.mean) on reducing external [Na+] from 144 to 20 mmol l−1, by replacement with Mg2+. Corresponding potency changes for other agonists were + 10.8 ± 2.5 for 3‐aminopropanesulphonic acid (3‐APS); 3.25 ± 1.06 for isoguvacine and 2.43 ± 0.69 for muscimol.
Nipecotic acid (0.5 mm) produced the following increases in potency: GABA 2.68 ± 0.82; 3‐aminopropanesulphonic acid, 3.11 ± 0.07; isoguvacine, 1.92 ± 0.34; muscimol, 2.24 ± 0.17.
The concentration of GABA in the bathing fluid necessary to double input conductance increased with increasing depth of the recording site from the cut surface. The apparent potency fell 10 times for each 60 μm depth increment up to 150 μm. The recording depth also affected the apparent potency of muscimol and 3‐APS but to a lesser extent. Reduction of external [Na+] reduced the depth‐dependence of both GABA and 3‐APS potency.
No clear change in the duration of the recurrent inhibitory postsynaptic conductance could be detected in the presence of 0.5 mmol l−1 nipecotic acid.
It is suggested that agonist uptake by a Na+‐dependent, nipecotic acid‐sensitive mechanism severely attenuates the responses of olfactory neurones to exogenous GABA and to its analogues 3‐APS, muscimol and isoguvacine, but has little immediate influence on the duration of the GABA‐mediated inhibitory postsynaptic conductance.
Influence of heart rate on the effects of prenalterol on regional myocardial blood flow and function during coronary stenosis in dogs
Authors: Berdeaux A. , Bonhenry C. , Duhazé P. , Giudicelli J.F. , Thuillez C. 
Published: July 2012

The effects of prenalterol, a selective β1‐adrenoceptor agonist with potent cardiac positive inotropic properties have been investigated on regional myocardial blood flow (RMBF) (microspheres) and contractile function (ultrasonic crystals) during partial circumflex coronary artery stenosis in 8 open‐chest anaesthetized dogs.
Prenalterol was investigated at two intravenous doses: 5 μg kg−1, which increased myocardial contractility (dP/dt max: +29%) more than heart rate (+ 12%, up to 150 beats min−1) and 20 μg kg−1 which induced almost similar increases in contractility (+35%) and heart rate (+31% up to 175 beats min−1). The induced modifications of regional flow and function were then compared to those produced in another series of 6 dogs by atrial pacing at 150 and 175 beats min−1 respectively.
Prenalterol significantly increased RMBF and segment length (SL)‐shortening in a dose‐dependent manner in the nonischaemic zone. In the ischaemic zone, RMBF was maintained and SL‐shortening increased with prenalterol, 5 μg kg−1 whereas both RMBF and contractile function were severely decreased with prenalterol, 20 μg kg−1.
Atrial pacing had almost no effect on RMBF and SL‐shortening in the nonischaemic zone. In the ischaemic zone, atrial pacing rate‐dependently decreased both RMBF and SL‐shortening.
Thus, a significant increase in contractility, associated with little tachycardia (prenalterol, 5 μg kg−1), induces beneficial effects on RMBF and function in both the nonischaemic and ischaemic myocardium. In contrast, a strong tachycardia, whether accompanied by positive inotropic effects (prenalterol, 20 μg kg−1) or not (atrial pacing at 175 beats min−1) induces deleterious effects on RMBF and cardiac function in the ischaemic myocardium.
A direct protective effect of sulphinpyrazone on ischaemic and reperfused rat hearts
Authors: Karmazyn Morris 
Published: July 2012

Initiation of 60 min ischaemia to rat isolated hearts produced a depression in developed tension and heart rate. Subsequent reperfusion caused a greatly exacerbated creatine phosphokinase (CPK) efflux and limited functional recovery.
Sulphinpyrazone (100 ng ml−1 and 1 μg ml−1) significantly reduced CPK release, particularly after reperfusion, the lower concentration being more effective.
A reduction in the mechanical depression during ischaemia and enhanced recovery after reperfusion were seen only with 100 ng ml−1 sulphinpyrazone. Heart rate and coronary perfusion pressure were unaffected by drug treatment.
The reduction in reperfusion‐induced CPK efflux by 100 ng ml−1 sulphinpyrazone was maximal when the drug was present throughout the perfusion period although some protection was evident when sulphinpyrazone was present either during ischaemia or reperfusion only. An enhanced recovery in contractility was seen only when the drug was present throughout all phases of perfusion.
It is suggested that sulphinpyrazone exerts a direct protective effect on the heart particularly during reperfusion. The degree of protection is critically dependent on the concentration of sulphinpyrazone.
Effects of the antagonists MDL 72222 and ketanserin on responses of cat carotid body chemoreceptors to 5‐hydroxytiyptamine
Authors: Kirby G.C. , McQueen D.S. 
Published: July 2012

The effects of intracarotid (i.c.) injections of 5‐hydroxytryptamine (5‐HT; 1–50 μg) on carotid chemoreceptor activity recorded from the carotid sinus nerve have been studied in anaesthetized cats.
Three separate components in the complex response of the chemoreceptors to injected 5‐HT were identified. Firstly, a transient burst of activity was obtained during the injection period in 56% of the recordings. Secondly, in all the recordings a period of chemodepression commenced a few seconds after completing the injection and was usually dose‐related. Thirdly, a delayed longer‐lasting chemoexcitation occurred in many experiments, concomitant with a fall in systemic blood pressure.
The neuronal 5‐HT receptor antagonist MDL 72222 (10–100 μg kg−1, i.c.) virtually abolished the transient chemoexcitation evoked during 5‐HT injections and also significantly increased the mean ID50 for 5‐HT‐induced chemodepression; in 37% of recordings 5‐HT caused a dose‐related chemoexcitation after the high dose of MDL 72222. Neither the delayed chemoexcitation nor the hypotension caused by 5‐HT were much affected by the antagonist. MDL 72222 itself had a biphasic effect on chemosensory discharge, causing depression followed by a delayed excitation.
The 5‐HT2‐receptor antagonist ketanserin (100 μg kg−1, i.c.) had no appreciable effect on the transient chemoexcitation evoked during 5‐HT injections and caused a slight but significant increase in the mean ID50 for 5‐HT‐induced chemodepression. The delayed chemoexcitation and accompanying hypotension associated with 5‐HT were both substantially reduced or abolished by the antagonist. Ketanserin itself caused a short‐lasting period of chemoexcitation.
All the effects of injected 5‐HT on chemosensory discharge could be abolished by the combination of MDL 72222 and ketanserin (100 μg kg−1, i.c.).
Neither MDL 72222 nor ketanserin had any significant effect upon the response of the carotid chemoreceptors to hypoxia. The rate at which discharge increased, and also the steady‐state discharge before and during hypoxia, were unaffected by the antagonists, alone or in combination.
At least two types of 5‐HT receptor appeared to be involved in the response of carotid body chemoreceptors to 5‐HT. Transient excitation and chemodepression wer*** mediated via MDL 72222‐sensitive (peripheral neuronal) receptors whereas the delayed chemoexcitation and associated hypotension involved a ketanserin‐sensitive, presumably 5‐HT2‐, receptor. It appears unlikely that 5‐HT plays a crucial role in chemoreception.
Interactions between receptors that increase cytosolic calcium and cyclic AMP in guinea‐pig liver cells
Authors: Cocks T.M. , Jenkinson D.H. , Koller Karin 
Published: July 2012

The action of agonists which increase the K+ permeability of liver cells was studied by using a K+‐sensitive electrode to record the net movement of K+ between guinea‐pig isolated hepatocytes and their suspension medium.
Two types of agonist were examined. Type 1 comprised angiotensin II, ATP, noradrenaline and amidephrine, all of which are thought to raise cytosolic Ca2+ in hepatocytes. The Type 2 agonists were isoprenaline and glucagon, which activate adenylate cyclase.
Each type of agonist initiated K+ loss from the hepatocytes though the response to Type 2 agonists was more variable than that to Type 1, and sometimes absent.
Simultaneous application of a small concentration of an agonist from each class caused a loss of K+ which was much larger than the sum of that seen with each agonist alone, i.e. potentiation occurred.
The α‐adrenoceptor antagonist, WB 4101, abolished potentiation if applied after an α‐agonist, and before a Type 2 agonist, showing that both receptors have to be active for potentiation to occur.
Simultaneous application of a maximal concentration of each type of agonist caused a larger loss of K+ (˜ 17% of the cell total within 45 s) than did a maximal concentration of a Type 1 agonist alone (˜ 10%).
Since the K+ loss caused by these agonists is thought to be a consequence of a rise in cytosolic Ca2+, the influence of both types of agonist on 45Ca and 42K efflux from guinea‐pig liver slices was studied.
The effect of isoprenaline on 45Ca and 42K efflux became much greater following a previous application of the α‐adrenoceptor agonist, amidephrine.
In the presence of apamin, the potentiated effect of isoprenaline on 42K efflux was greatly reduced whereas that on 45Ca efflux was little affected.
The effects of Type 1 and Type 2 agonists separately and together on the cyclic AMP content of isolated hepatocytes were examined. Type 2 agonists increased cyclic AMP in the expected way. The increase became slightly smaller, if anything, when a Type 1 agonist was applied at the same time. Hence potentiation could not be ascribed to changes in cyclic AMP formation.
Possible mechanisms for potentiation are discussed. Our evidence suggests, albeit indirectly, that it is a consequence of an interaction between the effects of the two types of agonist on cytosolic Ca2+.
A comparison of dimaprit, nordimaprit, methylamine and chloroquine as inhibitors of mitogen‐induced lymphocyte activation
Authors: Dale M. Maureen , Ladd R. 
Published: July 2012

Methylamine and chloroquine both ‘lysosomotropic’ agents (i.e. agents which sequester in lysosomes) caused a dose‐related inhibition of mitogen‐induced lymphocyte activation in the concentrations which have previously been shown to increase the pH of lysosomes.
The dose‐response curves of inhibition of mitogen‐induced lymphocyte activation for chloroquine and methylamine are very steep and are similar to the dose‐response curves obtained with dimaprit and nordimaprit, but very different from the flat dose‐response curves previously described for histamine. Approximate IC50 values were methylamine 6.4 mm, dimaprit 0.13 mm, nordimaprit 0.03 mm and chloroquine 18 μm.
It is suggested that the mechanism of action of methylamine and chloroquine may be related to their lysosomotropic action and consequent interference with ligand‐receptor processing, and that dimaprit and nordimaprit but not histamine may act by a similar mechanism.
In vivo platelet aggregation in the rat: dependence on extracellular divalent cation and inhibition by nonsteroidal anti‐inflammatory drugs
Authors: Mallarkey G. , Smith G.M. 
Published: July 2012

Using the Technicon Autocounter, the mechanisms involved in collagen‐induced platelet aggregation in vivo have been studied without the interference of an anticoagulant.
Extracellular divalent cation was essential for in vivo platelet aggregation.
Non‐steroidal anti‐inflammatory drugs completely inhibited the aggregation induced by collagen in platelet‐rich plasma in in vitro or ex vivo studies. In vivo only a maximum of 50% inhibition was achieved when release of thromboxane A2 (TXA2) was completely inhibited. Therefore in vivo, collagen causes aggregation through more than one pathway which operate independently of each other and which are all dependent on extracellular divalent cation.
In vivo, when different doses of collagen were compared, aggregation produced by low doses of collagen was more dependent upon prostaglandin endoperoxide/TXA2 formation.
Electromechanical effects of bepridil on rabbit isolated hearts
Authors: Anno Takafumi , Furuta Tatsuji , Itoh Masanori , Kodama Itsuo , Toyama Junji , Yamada Kazuo 
Published: July 2012

Electromechanical effects of a new antianginal agent, bepridil, on Langendorff‐perfused rabbit hearts were compared with those of verapamil and lidocaine.
Bepridil at concentrations above 2 × 10−7m caused a dose‐related decrease in heart rate (HR), a prolongation of the atrio‐His bundle conduction time (A‐H interval) and a prolongation of the functional refractory period (FRP) of the atrioventricular (A‐V) node. Similar changes in HR, A‐H interval and the FRP of the A‐V node were observed with verapamil at concentrations above 2 × 10−8m. Lidocaine at above 4 × 10−5m prolonged slightly the A‐H interval and the FRP of the A‐V node but did not decrease the HR.
Bepridil at concentrations above 10−6m prolonged both the His bundle‐ventricular conduction time (H‐V interval) and the effective refractory period (ERP) of ventricular muscles. Similar changes in the H‐V interval and in the ERP of ventricular muscles were observed with lidocaine at above 10−5m. Verapamil ranging between 5 × 10−8m and 8 × 10−7m had no effect on the H‐V interval and appreciably shortened the ERP of ventricular muscles.
Bepridil at concentrations above 2 × 10−6m reduced the developed tension as did verapamil at above 10−7m.
On a molar basis, the depressant effect of bepridil on HR and the A‐V nodal conduction, which may reflect inhibitory action on the slow channels, was less than one tenth that of verapamil. Bepridil was more potent than lidocaine in prolonging the H‐V interval and the ERP of ventricular muscles indicating a possible inhibition of the fast sodium channels. Both of these electrophysiological effects of bepridil may afford significant bases for the antiarrhythmic action of the drug.
Androgenic repression of hexobarbitone metabolism and action in Crl:CD‐1 (ICR)BR mice
Authors: Shapiro Bernard H. , Szczotka Susan M. 
Published: July 2012

Mice of the Crl:CD‐1 (ICR)BR strain exhibit a sexual dimorphism in hexobarbitone metabolism and action. Compared to females, males have a lower Vmax and a higher Km for hepatic microsomal hexobarbitone hydroxylase. In agreement with the enzyme studies, hexobarbitone‐induced sleeping times were greater for males than for females.
Results from experiments measuring hexobarbitone metabolism and action in castrate, testosterone and gonadotropin‐treated mice indicate that the sexual differences in drug metabolism and action found in Crl:CD‐1 (ICR)BR mice are due to the normally repressive effects of testicular androgens on the activities of the hepatic mono‐oxygenases. These findings are in dramatic contrast to studies with rats where it has been shown that androgens induce mono‐oxygenases. Furthermore, in the case of the mouse, changes in the activity of hexobarbitone hydroxylase in response to alterations in androgen levels require weeks, while in the rat, androgenic‐induced changes are apparent within a matter of days.
Vascular reactivity in rats with glycerol‐induced acute renal failure
Authors: Bowmer C. J. , Clarke Colette A. , Comer M. B. , Yates M. S. 
Published: July 2012

The vascular reactivity of rats with glycerol‐induced acute renal failure was assessed in vitro and in vivo.
The contractile responses to noradrenaline, angiotensin and potassium chloride of aortic strips and portal vein segments from uraemic rats were significantly smaller than the responses obtained in vessels from control animals.
The pressor responses to angiotensin were reduced significantly in rats with acute renal failure when compared to those in control rats.
The reduced vascular responses to a range of spasmogens suggests that in this model of renal failure there is a defect in some mechanism of vascular contraction common to all three constrictor agents.
Contractile responses to substance P and related peptides of the isolated muscularis mucosae of the guinea‐pig oesophagus
Authors: Kamikawa Yuichiro , Shimo Yasuo 
Published: July 2012

The site of action of substance P and related tachykinins with respect to isotonic contractions was examined on the isolated muscularis mucosae attached to the submucous plexus of the guinea‐pig oesophagus.
Substance P (> 30 nm) produced a concentration‐dependent contraction of the muscularis mucosae (EC50 1.9 ± 0.5 μm, n = 10). The contractions were rapid in onset (2 min or less), sustained, reversible by washing and the preparation did not show tachyphylaxis.
Eledoisin and physalaemin produced similar sustained contraction of the muscularis mucosae. The order of sensitivity was eledoisin > substance P > physalaemin. Contractions induced by 1 μm of each tachykinin were not significantly modified by incubation of the tissue with substance P or eledoisin (10 μm for 30 min).
The contractile responses to tachykinins were unaffected by tetrodotoxin (0.3 μm), atropine (0.3 μm), phentolamine (1 μm), chlorpheniramine (1 μM), methysergide (1 μM) baclofen (100 μm) and verapamil (10 μm), but were abolished by the incubation of the tissue with calcium‐free, EGTA (0.1 mm)‐containing Tyrode solution.
A substance P antagonist, [d‐Pro2, d‐Trp7,9]‐substance P (>0.1 μm), produced a transient contraction of the muscularis mucosae and the smooth muscle regained its original tone within 6 to 10 min. Contractions to the tachykinins were now inhibited by the antagonist (0.1–10 μm) in a concentration‐dependent manner, the order of sensitivity being physalaemin > substance P = eledoisin.
The cholinergically mediated electrically (0.1 Hz, 0.5 ms, supramaximal voltage)‐induced twitch contractions of the muscularis mucosae were not significantly modified by substance P (0.01–0.3 μm).
The present results indicate that substance P and related tachykinins contract the isolated muscularis mucosae of the guinea‐pig oesophagus by a direct action on the smooth muscle, probably by stimulating SP‐E receptors.
The response of cat spinal motoneurones to the intracellular application of agents with local anaesthetic action
Authors: Engberg I. , Flatman J.A. , Lambert J.D.C. 
Published: July 2012

QX‐222 (the trimethyl analogue of lignocaine), methylxylocholine, lignocaine and pentobarbitone were iontophoresed intracellularly into cat lumbosacral motoneurones. Iontophoresis and recording was either from a triple‐barrelled microelectrode unit or from two separately advanced microelectrodes.
QX‐222 and methylxylocholine caused a very slow reversible block of the current‐evoked and antidromic action potentials (AP) with no significant change of membrane potential (EM). Lignocaine had a minimal blocking effect on the AP.
No change, or only a small decrease, of membrane slope conductance (GM) was seen when the APs had been totally abolished.
QX‐222 and methylxylocholine reduced the massive Gm increase evoked by the passage of large depolarizing currents and converted the post‐current hyperpolarization (time constant 120–150 ms) into a depolarization of similar time course. It is suggested that the quaternary local anaesthetics can reduce the fast and slow voltage‐dependent potassium conductances.
Both agents totally blocked AP generation without decreasing the magnitude of the Ia e.p.s.p.
It is suggested that intracellularly iontophoresed QX‐222 (on account of its low lipid solubility) could be used as a pharmacological tool to block specifically the active Na and K channels in only the cell impaled by the microelectrodes.
Pharmacological studies into cyclo‐oxygenase, lipoxygenase and phospholipase in smooth muscle contraction in the isolated trachea
Authors: Mitchell H.W. 
Published: July 2012

Indomethacin (1 μm) enhanced histamine‐induced contractions in pig and guinea‐pig isolated tracheae. Mepacrine (30–50 μm) abolished this effect of indomethacin suggesting that contractile metabolites of arachidonate are involved in the response to indomethacin.
Mepacrine (100 μm) in the absence of indomethacin also markedly reduced histamine‐induced contractions (81.2% inhibition) in the pig trachea, without affecting responses to acetylcholine. Histamine‐induced responses in the guinea‐pig trachea were similarly reduced, but with a higher concentration of mepacrine (300 μm).
BW755c (226 μm) enhanced histamine‐induced contractions in some pig tracheal preparations and caused inhibition in others. These effects of BW755c were negatively correlated to the initial reactivity of the muscle to histamine such that weak contractions were potentiated and strong contractions were inhibited. A similar effect was seen with phenidone (100 μm).
The results with BW755c and phenidone suggest that muscle reactivity (to histamine) may be partly determined by the balance between the release of inhibitory and contractile arachidonate metabolites. Mepacrine exerts a different effect indicating that histamine‐induced contractions are regulated by a mepacrine‐sensitive process which appears to be separate from the metabolism of arachidonate.