bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of adrenoceptor agonists and antagonists on smooth muscle cells and neuromuscular transmission in the guinea‐pig renal artery and vein
Authors: Makita Yuji 
Published: July 2012

In the guinea‐pig renal artery and vein, the membrane potential was — 66.8 mV and — 46.8 mV, the length constant 0.54 mm and 0.43 mm, and the time constant 240 ms and 98 ms, respectively. The maximum slope of the depolarization produced by a 10 fold increase [K]o was 46 mV in the renal artery and 39 mV in the renal vein.
Noradrenaline (NA over 5 × 10−7m in the artery and over 10−7m in the vein) depolarized the membrane and slightly reduced the membrane resistance, assessed from relative changes in the amplitude of electrotonic potential. The action of NA was suppressed by prazosin in the artery but by yohimbine in the vein, i.e. the α1‐adrenoceptor is present in the extra junctional muscle membrane in the renal artery while the α2‐adrenoceptor is present in the renal vein. Dopamine and isoprenaline did not modify the membrane properties.
In the renal artery, repetitive perivascular nerve stimulation (0.1 ms, 50 Hz, 5 shocks) evoked excitatory junction potential (e.j.p.). Applications of guanethidine (10−6m) or tetrodotoxin (3 × 10−7m) abolished the generation of the e.j.p. Low concentrations of phentolamine (5 × 10−7 m), prazosin (10−7 m) and yohimbine (5 × 10−7 m) enhanced the e.j.p. amplitude, while high concentrations of phentolamine (10−5 m) and prazosin (> 10−5 m) reduced the amplitude of e.j.p.s. NA, dopamine and Clonidine consistently suppressed the amplitude of e.j.ps, at any given concentration over 10−7m.
Spontaneously generated miniature e.j.ps (m.e.j.ps) were recorded on rare occasions. Phentolamine and yohimbine both at 5 × 10−7m and prazosin 10−7m increased the appearance of m.e.j.ps.
In the renal vein, repetitive nerve stimulation failed to generate the e.j.p. Sympathetic innervation to this tissue seems to be sparse.
Specificity of innervation and adrenoceptors present on smooth muscle cells in both the renal artery and vein are discussed, and the presynaptic regulation of NA release is compared with findings in other vascular tissues.
Studies on an isolated innervated preparation of guinea‐pig trachea
Authors: Blackman J.G. , McCaig Dorothy J. 
Published: July 2012

An isolated preparation of the guinea‐pig trachea with intact parasympathetic and sympathetic innervation has been devised. Responses to nerve stimulation were recorded as increases or decreases in intraluminal pressure from the fluid‐filled trachea.
The preparation maintained a positive resting intraluminal pressure of 3–4 cmH2O. This was unaffected by atropine, hexamethonium or propranolol.
Brief pressor responses, which could be completely blocked by atropine or hexamethonium, were obtained by applying short trains of stimuli to the cervical segment of the right vagus. The amplitude of responses was frequency‐dependent up to a maximum at 40 Hz.
Depressor responses, more delayed and prolonged than the pressor responses and blocked by propranolol but not by hexamethonium, were obtained by stimulation of the right cervical sympathetic trunk or stellate ganglion in 70% of preparations. Dual pressor‐depressor responses were observed in the remaining 30% of preparations. The pressor component was blocked by atropine, the depressor component by propranolol.
In the presence of atropine and propranolol, sustained sympathetic stimulation sometimes evoked a small, delayed pressor response which was blocked by phentolamine.
Under the same conditions, transmural stimulation produced a depressor response evidently due to non‐adrenergic, non‐cholinergic nerves.
Spontaneous activity was observed in some preparations under normal conditions, but could always be evoked by hypoxia. Responses to sympathetic stimulation were reduced both by hypoxia and during periods of spontaneous activity.
The principal advantage of this preparation is that it permits both excitatory and inhibitory responses to be elicited by stimulation of vagal and sympathetic nerves separately in the isolated trachea in the absence of agonist and antagonist drugs.
Adenosine inhibits and potentiates IgE‐dependent histamine release from human basophils by an A2‐receptor mediated mechanism
Authors: Church Martin K. , Holgate Stephen T. , Hughes Philip J. 
Published: July 2012

Adenosine added to human basophils before anti‐IgE challenge inhibited histamine release, whereas addition after challenge potentiated release. Peak responses for the two effects occurred 15 min before and after challenge respectively.
The effects of adenosine on histamine secretion were dose‐related over concentration ranges of 1–100 μm for inhibition and 0.01–1 μm for potentiation.
The capacity of adenosine to inhibit and potentiate histamine secretion was inversely related to the strength of immunological challenge.
The ability of theophylline (50 μm) to inhibit and dipyridamole (1 μm) to enhance slightly adenosine‐induced responses, and the differing pharmacological effect of 2′,5′‐dideoxyadenosine suggested that adenosine's effects on basophil histamine secretion were mediated by stimulation of cell surface adenosine receptors.
The order of potency of adenosine and its analogues l‐ and d‐ N6‐phenylisopropyladenosine (PIA) and 5′‐N‐ethylcarboxamideadenosine (NECA) in inhibiting and potentiating IgE‐dependent histamine release from basophils indicated that both responses were mediated by stimulation of the adenosine A2‐receptor subtype.
The capacity of adenosine to cause a transient increase of cyclic AMP levels in 40–70% basophil‐enriched leucocytes confirmed the association between stimulation of A2‐receptors and activation of adenylate cyclase.
Barbiturates increase the rate of voltage‐dependent inactivation of the calcium current in snail neurones
Authors: Nishi K. , Oyama Y. 
Published: July 2012

Effects of barbiturates (thiopentone, pentobarbitone, phenobarbitone and barbitone) on the calcium current (ICa) in identified Helix neurones were studied, using a conventional suction pipette technique.
Barbiturates depressed the maximal peak amplitudes (MPA) of ICa in a dose‐dependent manner without shifting the current‐voltage relationships along the voltage axis.
Barbiturates accelerated the decay phase of ICa at high concentrations (1 × 10−4 to 3 × 10−3 m), at which concentrations double‐pulse experiments showed the increased rate of a voltage‐dependent inactivation of ICa.
It is concluded that the acceleration of the decay phase of ICa by barbiturates may be due to the increased rate of the voltage‐dependent inactivation of ICa.
Homotaurine: a GABAB antagonist in guinea‐pig ileum
Authors: Giotti A. , Luzzi S. , Spagnesi S. , Zilletti Lucilla 
Published: July 2012

Homotaurine (3‐aminopropane sulphonic acid) did not inhibit the twitch response in guinea‐pig ileum longitudinal muscle whilst γ‐aminobutyric acid (GABA) and (−)‐baclofen evoked dose‐dependent inhibitions.
The inhibitory effects of GABA and (−)‐baclofen were prevented in the presence of homotaurine 2 × 10−4 and 10−3 M.
The log dose‐effect curves of GABA and (−)‐baclofen were shifted in a parallel manner compatible with competitive antagonism. The pA2 of homotaurine with GABA (4.22 ± 0.05) and (−)‐baclofen (4.26 ± 0.1) were the same.
Homotaurine did not antagonize the inhibitory effects of morphine (ED50 4 × 10−7 M), noradrenaline (ED50 10−6 M) or ATP (ED50 1.5 × 10−5 M).
The inferior homologue of homotaurine, taurine 10−3 M, did not modify the inhibitory effects of GABA and (−)‐baclofen.
Picrotoxin 5 × 10−5 M antagonized GABAA receptor‐mediated contraction but did not affect GABAB receptor‐mediated inhibition. At the same concentration the drug did not influence the antagonistic action of homotaurine, thus showing no GABAA receptor‐mediated interference.
It may be concluded that homotaurine is a competitive antagonist of GABAB mediated effects in the guinea‐pig ileum.
The effects of chloroquine and other weak bases on the accumulation and efflux of digoxin and ouabain in HeLa cells
Authors: Griffiths N. , Lamb J.F. , Ogden P. 
Published: July 2012

We have studied the effects of the weak bases chloroquine, NH4Cl and amantadine on the handling of certain cardiac glycosides by HeLa cells.
When these weak bases are applied acutely to HeLa cells they have only minor effects on the binding of cardiac glycosides to the sodium pumps and on the recovery of pump function following block.
When cells are grown in these weak bases there is a variable (10–30%) reduction in pump numbers. This effect is additive to that of chronic treatment with cardiac glycosides.
If all sodium pumps are blocked with ouabain, digoxin or digitoxin then recovery of function recovers with a T1/2 of about 7 h (10% h−1); digoxin and digitoxin molecules are excreted at a similar rate but ouabain excretion occurs at a much slower rate (3% h−1).
These weak bases greatly slow (× 3) the rate of excretion of digoxin and digitoxin but do not alter that of ouabain. The process affected by chloroquine was estimated to have a T1/2 of 8 h.
Cells grown in the presence of cardiac glycosides accumulate large numbers of glycoside molecules; chloroquine, NH4Cl and amantadine increase the accumulation of digoxin and digitoxin and may decrease that of ouabain.
Quantitatively these results fit a model whereby cardiac glycosides are accumulated by HeLa cells bound to the sodium pumps, are processed by the lysosomes and then excreted.
The results are consistent with a process of internalisation and renewal of sodium pumps by HeLa cells.
β‐Adrenoceptor heterogeneity in guinea‐pig airways: comparison of functional and receptor labelling studies
Authors: Carswell Heather , Nahorski Stefan R. 
Published: July 2012

The distribution of β‐adrenoceptor subtypes in guinea‐pig airways has been studied by radioligand binding assays and analysis of mechanical responses.
Binding studies with the ligands [3H]‐dihydroalprenolol and [125I]‐cyanopindolol, revealed that β‐adrenoceptors were unevenly distributed throughout the airways with the highest density located in the parenchyma and the lowest density in the trachea.
The relative proportion of β1:β2‐adrenoceptor binding sites was assessed by computer‐assisted analysis of the inhibition curves generated by selective agents. It was virtually identical in each region and in the order of 15:85%.
β‐Adrenoceptor agonists caused concentration‐dependent relaxations of both tracheal spirals and parenchymal lung strips. This response appeared to be mediated by both β1‐ and β2‐adrenoceptors in tracheal spirals as the pA2 value for the β1‐selective antagonist, atenolol, varied depending upon which agonist was used, and, in the presence of the β2‐adrenoceptor antagonist ICI 118,551, noradrenaline and isoprenaline produced biphasic concentration‐effect curves. In parenchymal lung strips only the one subtype was involved as antagonist pA2 values were not dependent on the agonist used and the properties were consistent with those expected for a β2‐adrenoceptor.
Structure‐activity studies on the potentiation of benzodiazepine receptor binding by ethylenediamine analogues and derivatives
Authors: Morgan P.F. , Stone T.W. 
Published: July 2012

The effect of ethylenediamine analogues on in vitro binding of [3H]‐diazepam to crude cerebral cortical synaptosomal membranes in the rat was studied.
Ethylenediamine significantly increased [3H]‐diazepam binding to a maximum potentiation of 154% control (EC50 = 18 × 10−4 M) and was the most active compound studied in terms of both potency and the maximum potentiation observed.
Potentiation of [3H]‐diazepam binding by ethylenediamine analogues is dependent on carbon‐chain length, appears to require two terminal amino groups, and is not observed in the rigid analogues studied.
Potentiation of [3H]‐diazepam binding by ethylenediamine analogues is mediated largely by a change in receptor number and not receptor affinity.
Results are discussed in terms of the possible nature of the ethylenediamine binding site.
Effects of histamine and the histamine antagonists mepyramine and cimetidine on human coronary arteries in vitro
Authors: Godfraind T. , Miller R.C. 
Published: July 2012

The effects of histamine have been studied on human isolated coronary artery preparations taken from hearts ranging in age from 9 to 73 years.
Histamine in large concentrations (100 μM) contracted arteries which were without tone or spontaneous activity and sometimes induced rhythmic contractile activity. If spontaneous rhythmic activity was present it was enhanced by histamine. The contractile effects of histamine were inhibited by mepyramine but not by cimetidine.
Arteries which were contracted by depolarization responded with relaxation to histamine concentrations lower than those required to evoke a contraction; arteries from younger hearts were more sensitive than those from older hearts.
Mepyramine potentiated the maximal relaxant effect of histamine in arteries from hearts of all ages but cimetidine had very little effect.
In the presence of mepyramine, cimetidine antagonized the relaxant effect of histamine, shifting the concentration‐effect curve to the right.
It is concluded that human coronary arteries contain both H1‐ and H2‐type receptors, the H1‐receptors mediating contraction. The relaxant effects of histamine can only be inhibited by a combination of both H1‐ and H2‐receptor antagonists.
Yohimbine and prolongation of stimulation pulse duration alter similarly 3H‐transmitter efflux in heart: an alternative to the negative feedback hypothesis
Authors: Kalsner Stanley 
Published: July 2012

The hypothesis of negative feedback regulation of noradrenaline release was studied in guinea‐pig left atrial halves mounted in vitro.
Tissues were transmurally stimulated with 30, 100 or 300 pulses at 2 Hz with pulse durations ranging from 50 μS to 2,000 μS, and the efflux of 3H‐transmitter determined.
The efflux of tritium increased with increasing pulse duration as was anticipated, but the effects of supposed presynaptic antagonism by yohimbine were opposite to expectations for a negative feedback system. The magnification of efflux by yohimbine, compared to untreated controls was less rather than more as stimulation‐induced transmitter efflux climbed with increases in pulse duration, and with all other parameters of stimulation held constant.
It is concluded that the neuronal effect of yohimbine is not linked to negative feedback or to any other system sensing the perineuronal concentration of previously released transmitter.
Analysis of the effects on tritium efflux of yohimbine and of prolongation of the stimulation pulse duration, reveals a similarity in the way that they promote transmitter release. Yohimbine increased efflux to approximately the same value at all pulse durations between 50 and 1,000 μS and the value reached was equivalent to that obtained in untreated atria during stimulation with very long pulses (2,000 μS duration). It is suggested that yohimbine prolongs the outward current attributable to the efflux of potassium from axon terminals, and by this means prolongs depolarization and the period of transmitter release.
Tetraethylammonium (TEA), a quaternary ion known to plug potassium efflux channels, had an effect on transmitter efflux that was, in some ways, similar to that of yohimbine but of greater magnitude. The present findings provide, for the first time, an alternative to the hypothesis of negative feedback, that might explain the presynaptic effects of adrenoceptor antagonists and possibly other compounds.
Hypothalamic regulation of the cardiovascular and respiratory systems: role of specific opiate receptors
Authors: Faden Alan I. , Feuerstein Giora 
Published: July 2012

Experiments were designed to evaluate the role of μ and δ opiate receptors in central cardiovascular control in the hypothalamic nucleus preopticus medialis of rats anaesthetized with pentobarbitone.
The highly selective μ opiate receptor agonist D‐Ala2‐MePhe4‐Gly5‐ol‐enkephalin was extremely potent in eliciting hypotension and bradypnoea; tachycardia was elicited by a low dose (0.064 nmol), but not by higher doses (0.64–6.4 nmol).
Other selective μ receptor agonists (morphine sulphate, morphiceptin) caused tachycardia at lower doses (0.64, 6.4 nmol), hypotension and bradypnoea after the highest dose (64 nmol).
The relatively selective δ receptor agonist D‐Ala2‐D‐Leu5‐enkephalin caused profound bradypnoea and hypotension at the high dose (64 nmol), tachycardia after the lowest dose (0.64 nmol), but bradycardia was found during the hypotension induced by the high dose (64 nmol).
All of the opiate/opioid effects were reversed by naloxone (0.5 mg kg−1, i.v.).
It is concluded that μ receptors may mediate the cardiovascular and respiratory effects of opiates and opioid peptides in the nucleus preopticus medialis of the rat.
The relationship between stimulus‐induced antidromic firing and twitch potentiation produced by paraoxon in rat phrenic nerve‐diaphragm preparations
Authors: Clark A.L. , Hobbiger F. , Terrar D.A. 
Published: July 2012

The relationship between stimulus‐induced repetitive antidromic firing (ADF) in the motor nerve and twitch potentiation produced by the organophosphate anticholinesterase paraoxon, has been investigated in rat diaphragm preparations.
Little or no ADF was produced by paraoxon in preparations bathed in a Tyrode solution containing 1 mM calcium and 1 mM magnesium ions although the preparations showed marked twitch potentiation.
Increases in the calcium: magnesium ion ratio produced a ratio‐dependent increase in the ADF but had no consistent effect on peak twitch potentiation.
Dithiothreitol, a disulphide bond reducing agent which decreases the affinity of acetylcholine for nicotinic cholinoceptors, abolished ADF but only modified the time course of twitch potentiation.
It is concluded that the initiation of ADF is a consequence of the prolonged action of acetylcholine within the synaptic cleft following inhibition of acetylcholinesterase, and that ADF is not the only mechanism by which twitch potentiation can be produced.
Inhibition of gastric acid secretion in the conscious dog by the mast‐cell stabilizing agent, FPL 52694
Authors: Canfield S.P. , Curwain B.P. 
Published: July 2012

The effects of the mast‐cell stabilizing agent, FPL 52694, on gastric acid secretion in conscious dogs with gastric fistulae have been studied.
FPL 52694 (5 or 10 mg kg−1 h−1) given intravenously during a plateau response to pentagastrin stimulation (2 μg'kg−1 h−1) caused a maximum inhibition of acid output of about 50% but had no significant effect on volume output so that the [H+] in the juice was markedly reduced. The ratio of mucosal blood flow/acid output (Ra) was increased in the presence of FPL 52694. There was no maintained reduction of [H+] when inhibition was due to cimetidine (4 μmol kg−1, i.V.).
Instillation of FPL 52694 (4.35 mg ml−1) directly into the stomach via the fistula for 30 min also resulted in an inhibition of acid output and reduction of [H+] during both pentagastrin‐(2 μg kg−1 h−1) and histamine‐stimulated (30 μg kg−1 h−1) secretion. Inhibition of pentagastrin‐stimulated acid output by intragastric administration of FPL 52694 was much greater than the maximum effect seen following intravenous infusion.
The results are discussed in relation to the possible mode of action of FPL 52694. It is concluded that FPL 52694 is active orally and has a novel action on acid secretion which may include stimulation of gastric bicarbonate secretion.
A comparison of the electrophysiological actions of phentolamine with those of some other antiarrhythmic drugs on tissues isolated from the rat heart
Authors: Northover B.J. 
Published: July 2012

Glass microelectrodes were used to record transmembrane electrical activity from cells located just beneath the endocardial surface of segments from the atrial and right ventricular free walls of rat hearts during superfusion and electrical stimulation in vitro at 37°C.
Availability of the fast sodium channels for current flow was inferred from the maximum rate of rise of membrane potential during phase 0 of the action potential.
Phentolamine mesylate (2 to 20 μM) caused a concentration‐dependent block of the fast sodium channel. This was reflected in prolongation of the refractory period and slowing of recovery of excitability following the action potential, without significant change in action potential duration or resting membrane potential.
Increase in the concentration of KCl in the superfusate from 5 to 10 mM depolarized the muscle and potentiated the blocking action of phentolamine. Both the depolarizing and the phentolamine‐potentiating actions of KCl were counteracted by simultaneous elevation of the concentration of CaCh in the superfusate from 2 to 10 mM.
The blocking action of phentolamine was enhanced by increasing the frequency of electrical stimulation in the range 0.01 to 10 Hz.
In respect of the properties listed above, lignocaine hydrochloride was similar to phentolamine but was different from quinidine sulphate in that the effects of the latter drug were not potentiated by KCl.
Two other α‐adrenoceptor antagonists, prazosin and yohimbine, both displayed actions similar to those shown by phentolamine. Tolazoline was only weakly active and dihydroergotamine (60 μM) was inactive. Dibenamine and phenoxybenzamine, unlike the previously named drugs, caused an irreversible block of the fast sodium channel. These blocking actions of α‐adrenoceptor antagonists were not prevented by simultaneous exposure to the α‐adrenoceptor agonist phenylephrine (1 HIM).
Muscle from both reserpine pretreated and non‐pretreated rats responded indistinguishably to phentolamine.
Tyramine‐induced noradrenaline release from rat brain slices: prevention by (‐)‐deprenyl
Authors: Glover Vivette , Pycock C.J. , Sandler M. 
Published: July 2012

Clorgyline (1 and 10 μM) and (+)‐deprenyl (10 μM) both significantly potentiated the tyramine (100 μM)‐induced release of [3H]‐noradrenaline from rat cerebral cortex slices. (‐)‐Deprenyl (50 μM) significantly reduced it, while lower concentrations had no effect on noradrenaline release. However, in combination, 1 μM (‐)‐deprenyl blocked the release‐facilitating action of 1 μM clorgyline, and 10 μM (‐)‐deprenyl that of 10 μM (+)‐deprenyl.
Low concentrations of (+)‐ and (‐)‐deprenyl (1 and 10 μM), both selectively inhibited phenylethylamine oxidation by monoamine oxidase B. Higher concentrations of (‐)‐deprenyl (20 and 50 μM) also inhibited 5‐hydroxytryptamine oxidation by monoamine oxidase A. Clorgyline (1 and 10 μM) inhibited both enzymes. Thus, the effects of these drugs on noradrenaline‐release cannot be explained solely in terms of irreversible inhibition of monoamine oxidase A and B, and other possible mechanisms are discussed.
If the brain‐slice model faithfully mirrors the sequence of events manifesting peripherally as the tyramine hypertensive response (‘cheese effect”), then it is possible that low doses of (‐)‐deprenyl, administered with antidepressant monoamine oxidase inhibitors, can prevent this adverse reaction.
Evidence for pharmacological similarity between α2,‐adrenoceptors in the vas deferens and central nervous system of the rat
Authors: Doxey J.C. , Gadie B. , Lane A.C. , Tulloch I.F. 
Published: July 2012

Seven α2‐adrenoceptor antagonists with diverse chemical structures have been examined for their effects at α2‐adrenoceptors in the vas deferens and central nervous system of the rat.
Antagonist potency assessed against the presynaptic α2‐adrenoceptor agonist action of clonidine in the isolated vas deferens (RX 781094 > AWy 26703 > yohimbine > rauwolscine > piperoxan > mianserin > RS 21361) was highly correlated with the ability of these drugs to displace saturable [3H]‐RX 781094 binding from cerebral cortex membranes.
Similarly, antagonist potency in the vas deferens was highly correlated with antagonist activity in reversing the centrally‐mediated mydriasis induced by the selective α2‐adrenoceptor agonist, guanoxabenz, in pentobarbitone‐anaesthetized rats.
The results indicate that the presynaptic α2‐adrenoceptors in the vas deferens are pharmacologically similar to characterized these α2‐adrenoceptors in the central nervous system of the rat.