bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of pentobarbitone on acetylcholine‐activated channels in mammalian muscle
Authors: Gage Peter W. , McKinnon David 
Published: July 2012

Acetylcholine‐activated single channel currents were recorded from the extrajunctional region of chronically denervated skeletal muscle of the rat by the patch clamp technique.
In control experiments, the cumulative open‐time, closed‐time and burst length distributions could be well described by the sum of two exponentials.
Pentobarbitone decreased the mean open time and increased the time constant of the fast component of the closed time distribution. These effects increased with drug concentration.
The mean burst length was relatively independent of pentobarbitone concentration over the range of concentrations used (10–500 μM).
These observations are inconsistent with a simple sequential blocking model and it is suggested that pentobarbitone has an allosteric site of action on receptor‐channel complexes that makes the open state less stable.
Desensitization of prostacyclin responsiveness in a neuronal hybrid cell line: selective loss of high affinity receptors
Authors: Leigh P. J. , MacDermot J. 
Published: July 2012

The binding of [3H]‐iloprost (ZK36374) to NCB‐20 membranes revealed a single population of high affinity receptors (KD = 9.55 nM, Bmax = 431 fmol mg−1 protein) and a low affinity, non‐saturable binding component.
Desensitization of prostacyclin‐responsiveness of NCB‐20 cells is induced by culture in the presence of the stable protacyclin analogue carbacyclin. Desensitization is accompanied by an increase in the Kact value for prostacyclin (64.1 nM to 175 nM), and a reduction in the prostacyclin‐dependent increase in adenylate cyclase activity (41.2 to 15.1 pmol cyclic AMP min−1 mg−1 protein).
Desensitization is not accompanied by changes in the coupling of the catalytic (C) to the regulatory (Ns) subunit of adenylate cyclase. In addition, the physical identity of the receptor molecule (as characterized by its sensitivity to electron bombardment in the beam of a linear accelerator) is not changed by desensitization.
Desensitization of prostacyclin‐dependent activation of adenylate cyclase may be explained most simply by a loss of prostacyclin receptors. The anomalous increase in the Kact (concentration of prostaglandin giving half‐maximum enzyme activation) for prostacyclin‐stimulated adenylate cyclase was not accompanied by a substantial change in the KD of [3H]‐iloprost binding, and is explained by a loss of spare receptors.
Prostacyclin responsiveness in non‐dividing cells may be restored after desensitization by prolonged culture (up to 48 h) in the absence of carbacyclin. Resensitization is accompanied by restoration of the high affinity Kact value (143 nM to 45.5 nM), and is dependent on de novo protein synthesis.
Interaction of prostaglandin D2 with prostacyclin, carbacyclin and the hydantoin prostaglandin, BW245C, in guinea‐pig platelets
Authors: Hamid S. , Whittle B.J.R. 
Published: July 2012

The anti‐aggregating actions of prostaglandin D2 (PGD2) have been compared to prostacyclin (PGI2), its stable analogue carbacyclin and a hydantoin prostaglandin, BW245C, in guinea‐pig platelets in vitro.
PGI2, carbacyclin and BW245C were potent inhibitors of ADP‐induced aggregation in guinea‐pig platelets, with ID50 values comparable to those obtained in human platelet‐rich‐plasma.
In contrast, PGD2 acted as a weak and partial inhibitor in guinea‐pig platelet aggregation, producing a bell‐shaped dose‐response relationship.
PGD2 induced a dose‐related antagonism of the inhibitory actions of BW245C, prostacyclin and carbacyclin on guinea‐pig platelets.
However, PGD2 did not antagonize the inhibitory actions of either forskolin or dibutyryl cyclic AMP on this platelet preparation.
The results suggest a non‐specific interaction of PGD2 with these prostanoid binding sites on guinea‐pig platelets.
Inhibitory effects of forskolin and papaverine on nerve conduction partially blocked by tetrodotoxin in the frog sciatic nerve
Authors: Ribeiro J.A. , Sebastião A.M. 
Published: July 2012

The effects of forskolin, sodium fluoride and papaverine on compound action potentials were investigated in de‐sheathed sciatic nerve preparations of the frog.
Forskolin decreased in a concentration‐dependent manner the amplitude of compound action potentials when nerve conduction was partially blocked by tetrodotoxin (TTX). In the presence of TTX a 50% decrease in the action potential amplitude recorded was obtained with about 2.5 μM forskolin.
Sodium fluoride did not modify the amplitude of compound action potentials partially blocked by TTX.
Papaverine also decreased the amplitude of compound action potentials partially inhibited by TTX. A 50% decrease in the action potential amplitude recorded in the presence of TTX was obtained with about 10 μM papaverine.
The possibility that cyclic AMP modulates axonal excitability by interfering with the entry of sodium through the TTX‐sensitive sodium channel is discussed.
Erythrosin B inhibits high affinity ouabain binding in guinea‐pig heart Na+‐K+‐ATPase without influence on cardiac glyoside induced contractility
Authors: Fricke Uwe 
Published: July 2012

Binding of [3H]‐ouabain to guinea‐pig heart membranes enriched in Na+‐K+‐ATPase revealed two different cardiac glycoside binding sites. High affinity binding was obtained at a KD = 2.2 × 10−7 mol 1−1 (Bmax = 16.8 pmol ouabain mg−1 protein) whereas low affinity ouabain binding occurred at a KD > 10−6 mol 1−1.
To discover whether the two ouabain binding sites are functional in guinea‐pig heart muscle, erythrosin B, an inhibitor of the high affinity ouabain binding in rat brain tissue, was tested in guinea‐pig isolated heart muscle preparations. Erythrosin B proved to be a potent inhibitor of the Mg2+(Na+)‐dependent‐, as well as Na+‐K+‐activated ATPase (ID50 = 9 × 10−6 mol 1−1). Contractility of guinea‐pig isolated papillary muscles, however, was not influenced by erythrosin B in concentrations up to 1 × 10−5 mol 1−1. Only very high concentrations (4 × 10−4 mol 1−1) resulted in a slightly negative inotropic effect (about 20%).
Erythrosin B dose‐dependently inhibited [3H]‐ouabain binding to the Na+‐K+‐ATPase (KD = − 3.6 × 10−6 mol 1−1). In a concentration of 1 × 10−5 mol 1−1 the dye abolished high affinity [3H]‐ouabain binding without affecting the low affinity binding sites.
In contrast, in guinea‐pig isolated atria, no functional antagonism between erythrosin B (5 × 10−5 mol 1−1) and ouabain was observed.
As there is a coincidence between the high affinity binding (KD = 2.2 × 10−7 mol 1−1) and the concentration for half maximum inotropic effects of ouabain (ED50 = 1.6 × 10−7 mol 1−1), the lack of effect of erythrosin B on ouabain‐induced inotropy may be caused by an inaccessibility of the dye to the (internal) ATP‐site of the Na+‐K+‐ATPase.
Autoradiographic localization of β‐adrenoceptor subtypes in guinea‐pig kidney
Authors: Lew R. , Summers R.J. 
Published: July 2012

The distribution of β‐adrenoceptor subtypes in slide‐mounted sections of guinea‐pig kidney has been examined by the technique of in vitro labelling combined with autoradiography.
Binding of (‐)‐[125I]‐cyanopindolol (Cyp) to kidney sections equilibrated and dissociated slowly, was saturable and stereoselective with respect to the isomers of propranolol and pindolol. These characteristics were appropriate for binding to β‐adrenoceptors.
Delineation of β‐adrenoceptor subtypes was achieved by use of betaxolol (β1‐adrenoceptors) and ICI 118,551 (β2‐adrenoceptors) and computer assisted curve fitting techniques. Both β1‐ and β2‐adrenoceptors were present in the proportions 1:2.
3H‐Ultrofilm images of (‐)‐[125I]‐Cyp binding to guinea‐pig kidney sections showed localized patches of binding in the cortex and concentrated binding in the outer stripe of the medulla. Cortical receptors were of the β1 subtype and those associated with the outer stripe of the medulla were of the β2‐adrenoceptor subtype. β1‐Adrenoceptors were concentrated over glomeruli and β2‐adrenoceptors over the straight portion of the proximal tubule.
[3H]‐rauwolscine binding to α2‐adrenoceptors in the mammalian kidney: apparent receptor heterogeneity between species
Authors: Neylon C.B. , Summers R.J. 
Published: July 2012

Binding of the α2‐adrenoceptor antagonist [3H]‐rauwolscine was characterized in membrane preparations from the kidneys of mouse, rat, rabbit, dog, and man.
In all species, binding reached equilibrium within 45 min and dissociated at a single exponential rate after addition of phentolamine 10 μM.
Saturation studies showed that the affinity of [3H]‐rauwolscine was similar in all species (2.33‐3.03 nM) except man where it was significantly higher (0.98 nM). Marked differences were seen in the density of binding sites, increasing in the order: man < dog < rabbit < rat < mouse. In all cases, Hill coefficients were not significantly different from unity.
[3H]‐rauwolscine binds with low affinity (KD > 15 nM) to membranes prepared from guinea‐pig kidney. The low affinity binding is not due to the absence of particular ions in the incubation medium or to receptor occupation by endogenous agonist.
The binding in all species was found to be stereoselective with respect to the isomers of noradrenaline. However, differences were seen in the characteristics of agonist interactions with the binding site both between isomers and between species.
Marked differences in affinity of particular α‐adrenoceptor antagonists were observed for α2‐adrenoceptors labelled by [3H]‐rauwolscine. These differences were most evident with the α1‐adrenoceptor selective antagonist prazosin which displayed inhibition constants (Ki values) of 33.2, 39.5, 261, 570 and 595 nM in rat, mouse, dog, man and rabbit, respectively.
Differences are apparent in the characteristics of α2‐adrenoceptors labelled by [3H]‐rauwolscine between species and it is suggested that the differences observed for α1‐selective antagonists such as prazosin may be related to binding to additional sites in the vicinity of the α2‐adrenoceptor.
Regional variation in the sensitivity of longitudinal smooth muscle to histamine at H1‐receptors in guinea‐pig ileum and colon
Authors: Barker L.A. 
Published: July 2012

The sensitivity of the distal ileum, proximal colon, medial colon, and distal colon of the guinea‐pig to histamine has been evaluated.
The rank order of sensitivity was ileum > medial colon > proximal colon ∼ distal colon.
The mean ‐ log EC50 values at receptors in the ileum, medial, proximal, and distal colon were 6.74, 6.18, 5.79, and 5.72, respectively.
The apparent dissociation constant for the interaction of histamine with receptors in the various regions was determined.
The ‐ log Kd values at receptors in the ileum, proximal colon, medial colon, and distal colon were 4.68, 4.65, 4.62, and 4.44, respectively.
The mean apparent ‐ log Kd values for the antagonism of histamine by mepyramine were 9.0, 9.0, 9.1, and 8.9 for receptors on the ileum, proximal, medial, and distal colon, respectively.
The results of these experiments provide no evidence that histamine receptors in the colon are distinguishable from H1‐preceptors as characterized on the ileum.
The differences in sensitivity to histamine in the various regions of the intestine may be due to differences in the density of H1‐preceptors.
Actions of dihydroavermectin B1α on insect muscle
Authors: Duce I.R. , Scott R.H. 
Published: July 2012

Muscle bundle 33 of the locust (Schistocerca gregaria) extensor tibiae muscle, which is sensitive to γ‐aminobutyric acid (GABA) and receives inhibitory innervation, exhibited both reversible and irreversible responses to dihydroavermectin B1α (DHAVM). These responses involved increases in Cl− permeability.
DHAVM (0.000075‐0.0075 μg ml−1) induced reversible dose‐dependent increases in Cl− permeability and partially blocked GABA‐induced Cl− conductance. These effects appear to be due to an interaction of DHAVM with the GABA receptor‐Cl− ion channel complex.
DHAVM (0.01‐1.0 μg ml−1) induced an irreversible increase in Cl− conductance which continued to rise after DHAVM application was stopped. At these concentrations DHAVM potentiated GABA‐induced Cl− conductances which were in turn reduced by microperfusion of DHAVM (0.01‐1.0 μg ml−1) during bath application of GABA.
DHAVM (0.0001‐1.0 μg ml−1) induced only irreversible increases in Cl− conductance when applied to fast muscle bundles (21–26) of the locust extensor tibiae muscle, which are GABA‐insensitive and have no inhibitory innervation.
The actions of DHAVM on locust muscle appear to involve more than one site. Reversible actions of DHAVM appear to be related to GABA sensitivity and may involve the GABA receptor‐ionophore complex. This is unlikely to be the site of action for the irreversible increases in Cl− conductance caused by DHAVM.
The relative potencies of some agonists at M2 muscarinic receptors in guinea‐pig ileum, atria and bronchi
Authors: Barlow R.B. , Weston‐Smith Penelope 
Published: July 2012

The effects of some agonists on isolated preparations of guinea‐pig ileum, atria and bronchial muscle have been compared with those of carbachol. The concentrations producing comparable responses were used to estimate the equipotent molar ratio relative to carbachol.
Arecaidine propargyl ester was 4 to 5 times as active as carbachol on the ileum but more than 10 times as active as carbachol on atrial rate or atrial force, so the results confirm that this compound has a 2 to 3 fold selectivity for receptors in atria.
Ethoxyethyltrimethylammonium iodide was one‐quarter to one‐third as active as carbachol on ileum but only one‐tenth as active as carbachol on atrial rate or atrial force and so shows a 3 to 4 fold selectivity for receptors in ileum.
The other compounds tested, which included acetylcholine, methacholine, n‐pentyltrimethyl‐ammonium iodide and bethanechol showed less selectivity.
There were no obvious differences between effects on atrial rate and effects on atrial force, though with esters it was often difficult to obtain effects on atrial rate in the absence of an inhibitor of cholinesterase.
Activity on bronchial muscle was generally similar to activity on ileum.
Selective effects of thiol reagents on the binding sites for imipramine and neurotransmitter amines in the rat brain
Authors: Biassoni Roberto , Vaccari Andrea 
Published: July 2012

The action of the antithyroid drugs methimazole (MMI) and propylthiouracyl (PTU) on the binding of [3H]‐imipramine, [3H]‐5‐hydroxytryptamine ([3H]‐5‐HT) (to 5‐HT1‐receptors) and [3H]‐spiperone (to 5‐HT2‐, D2‐receptors) of rat brain membranes has been examined. The synaptosomal uptake of [3H]‐5‐HT was also studied.
Micromolar concentrations of the disulphide bond reducing agents MMI, PTU, dithiothreitol (DTT) and mercaptoethanol increased both the binding of [3H]‐imipramine and the uptake of [3H]‐5‐HT. In contrast, they decreased the number of 5‐HT1‐receptors, and did not affect 5‐HT2‐ and D2‐sites.
Reaction with membrane‐bound sulphydryl (SH) groups by micromolar concentrations of N‐ethylmaleimide (NEM), hydroxymercuribenzoic acid (PCMB), or Ellman's reagent (DTNB) decreased the binding of [3H]‐imipramine, the number of 5‐HT1‐receptors, and the uptake of [3H]‐5‐HT. Millimolar concentrations of NEM were necessary in order to decrease partially 5‐HT2‐ and D2‐receptors.
The effects of NEM on imipramine recognition sites and on the uptake of 5‐HT could be prevented by DTT; protection was not obtained in other receptor systems.
Three groups of receptors have been, thus, postulated, based upon their different sensitivity towards alterations in membrane [disulphide bridges SH] equilibrium: Group I, including imipramine recognition sites and the uptake system for 5‐HT; Group II, including 5‐HT]‐receptors; Group III, including 5‐HT2‐ and D2‐receptors.
No inotropic action of enkephalins or enkephalin derivatives on electrically‐stimulated atria isolated from lean and obese rats
Authors: Saunders W.S. , Thornhill J.A. 
Published: July 2012

Inotropic actions of the endogenous enkephalins, leucine enkephalin ([Leu] enkephalin) and methionine enkephalin ([Met] enkephalin), and derivatives, [D‐Ala2‐methionine] enkephalinamide (DAMEA) and [D Ala2‐leucine]enkephalinamide (DALEA) were tested, alone or in combination with noradrenaline (NA), (±)‐isoprenaline or carbachol, on electrically‐stimulated atria excised from Sprague‐Dawley, fatty, Zucker (fa/fa) and lean, hooded heterozygous (Fa/fa) rats.
[Met] enkephalin, [Leu] enkephalin, DAMEA and DALEA (4 × 10−7 M to 4 × 10−4 M) caused no significant changes in atrial tension in any group compared to pre‐injection control values or those following the infusion of Krebs‐Henseleit control solution.
NA and isoprenaline (10−7 to 10−6 M) caused significant, dose‐related increases in atrial tension in each of the three strains of rats tested with the Fa/fa group showing the greatest change and fastest rate of tension development. [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 × 10−6 M) infused concurrently with NA or isoprenaline (10−6M) evoked atrial tension changes within each group that were not different from those observed when NA or isoprenaline was administered alone.
Carbachol (10−9 and 10−8M) caused a dose‐related decrease (10% and 30–40%, respectively, from pre‐injection control values) in atrial tension in auricles excised from all three groups. Again, infusion of [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 × 10−6M) together with carbachol (10−8M) did not affect atrial tension changes of auricles isolated from any group compared to when carbachol was given alone.
The results indicate that the endogenous pentapeptides, ([Met] or [Leu] enkephalin), or derivatives (DAMEA and DALEA) do not affect atrial tension of electrically‐stimulated auricles isolated from Sprague‐Dawley, fa/fa or Fa/fa rats. In addition, these pentapeptides do not modify the positive inotropic actions of NA or isoprenaline or the negative inotropic effects of carbachol. It is suggested that in vivo, the enkephalins or enkephalin derivatives do not have a direct action on the heart to alter myocardial contractility.
The cardiovascular and platelet actions of 9β‐methyl carbacyclin (ciprostene), a chemically stable analogue of prostacyclin, in the dog and monkey
Authors: Allan G. , Follenfant M.J. , Lidbury P. , Oliver P.L. , Whittle B.J.R. 
Published: July 2012

9β‐Methyl carbacyclin (9βMe; ciprostene) is a synthetic, chemically stable analogue of prostacyclin (PGI2; epoprostenol). The platelet anti‐aggregating and cardiovascular effects of 9βMe have been compared to PGI2 in anaesthetized monkeys and dogs. In addition, their haemodynamic effects have been compared in open‐chest anaesthetized dogs and conscious dogs.
Intravenous infusion of 9βMe and PGI2 to the anaesthetized monkey resulted in a dose‐dependent hypotension, tachycardia and inhibition of ex vivo ADP‐induced platelet aggregation. 9βMe was 72 times less active than PGI2 both as a hypotensive and anti‐aggregating agent.
Intravenous infusion of 9βMe and PGI2 to the anaesthetized beagle dog resulted in a qualitatively similar haemodynamic profile. Thus both substances induced a dose‐dependent hypotension accompanied initially by a slightly increased heart rate, a dose‐dependent increase in cardiac output, stroke volume and an increased peak LV dP/dt. At the higher doses studied, the initial increases in the parameters measured were succeeded by dose‐dependent falls. 9βMe was 76 times less active than PGI2 as a hypotensive agent.
In the anaesthetized greyhound, a dose‐dependent anti‐aggregating and hypotensive effect was seen with either drug, with 9βMe being 23 and 40 times less active than PGI2, respectively.
Intravenous infusion of 9βMe and PGI2 to the conscious beagle dog induced a dose‐dependent hypotension and a variable effect on heart rate. 9βMe was 33 times less active than PGI2 as an hypotensive agent.
The duration of the hypotensive response induced by 9βMe was not significantly different from that induced by PGI2 in either monkey or beagle dog.
Pharmacological characterization of D‐aminophosphonovaleric acid antagonism of amino acid and synaptically evoked excitations on frog motoneurones in vitro: an intracellular study
Authors: Corradetti R. , King Anne E. , Nistri A. , Rovira Catherine , Sivilotti Lucia 
Published: July 2012

The effect of D‐aminophosphonovaleric acid (D‐APV) on the depolarizations induced by N‐methyl‐D‐aspartate (NMDA), glutamate, aspartate or quisqualate was studied with intracellular recordings from frog motoneurones in vitro.
D‐APV (0.5–10 μM) produced a slight hyperpolarization of the motoneuronal membrane without significant changes in input conductance.
In control and tetrodotoxin‐containing solutions the depolarizations induced by NMDA were strongly reduced by D‐APV while quisqualate depolarizations were unaffected. Responses to glutamate and aspartate were antagonized to an intermediate level. The relatively small conductance increases evoked by excitatory amino acids were unaltered in solutions containing D‐APV.
The amplitude of monosynaptic excitatory postsynaptic potentials (e.p.s.ps) was strongly depressed by D‐APV. The amplitude of polysynaptic e.p.s.ps was little changed but their decay time was reduced.
It is suggested that D‐APV is a powerful and selective NMDA receptor antagonist and that an endogenous amino acid acting via NMDA receptors may be the transmitter of monosynaptic e.p.s.ps on frog motoneurones.
The positive inotropic action of the nifedipine analogue, Bay K 8644, in guinea‐pig and rat isolated cardiac preparations
Authors: Finet M. , Godfraind T. , Khoury G. 
Published: July 2012

The inotropic effect of Bay K 8644 has been studied in rat and guinea‐pig atria and ventricular strips stimulated at 1 Hz, in a medium containing CaCl2 1.8 mM. The positive inotropic effect at maximal effective concentrations of Bay K 8644 was in the following order: guinea‐pig ventricle > rat ventricle > guinea‐pig atria >> rat atria.
In rat preparations, the tension recorded at maximum effective concentrations of Bay K 8644 was similar at three different calcium concentrations (0.7, 1.8, 3.0 mM). The amplitude of the positive inotropic effect evoked by Bay K 8644 increased when atrial and ventricular contractions were reduced by lowering the external calcium concentration.
The contractile tension reached in the presence of maximum effective concentrations of Bay K 8644 (3 × 10−7 − 1 × 10−6 M) was greater than that produced by the maximum effective concentration of external calcium (3 mM) in rat ventricles but not in rat atria.
High doses of nifedipine (3 × 10−7 − 1 × 10−6 M) depressed the contraction of rat atria more than the contraction of rat ventricles.
In rat ventricles, nifedipine shifted to the right the inotropic dose‐effect curve of Bay K 8644.
It is concluded that the interaction between nifedipine and Bay K 8644 occurred at the same binding sites. These sites have some characteristics of the low affinity binding sites of nifedipine and other related dihydropyridines.