bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is co‐transmission involved in the excitatory responses of the rat anococcygeus muscle?
Authors: Cunnane T.C. , Muir T.C. , Wardle Kay A. 
Published: July 2012

Electrical and mechanical responses to field (transmural) and extrinsic nerve stimulation were recorded simultaneously in the rat anococcygeus muscle. Membrane potential changes recorded intracellularly following either method of stimulation were indistinguishable. Single stimuli usually produced a slow depolarization; trains of pulses produced a fast excitatory junction potential (e.j.p.) initially, followed by a slow depolarization similar to that produced by single pulses. The fast e.j.ps, the slow depolarizations and the accompanying contractions were abolished by the α‐adrenoceptor antagonists, phentolamine (1 × 10−6 m) or prazosin (1 × 10−7 m) and by tetrodotoxin (TTX, 1 × 10−6 m) but unaffected by α, β‐methylene adenosine triphosphate (α, β‐MeATP, 1–10 × 10−6 m), an agent known to desensitize purinoceptors.
Application of noradrenaline (NA, 1 × 10−8‐1 × 10−6 m), by pressure ejection from a micropipette, depolarized the membrane and produced a localized contraction, both of which were abolished by phentolamine (1 × 10−6 m) or prazosin (1 × 10−7 m).
Application of adenosine‐5′‐triphosphate (ATP, 1 × 10−4‐1 × 10−3 m), by pressure ejection from a micropipette, produced a small membrane depolarization and localized contraction which were unaffected by phentolamine (1 × 10−6 m) or prazosin (1 × 10−7 m) but abolished by α, β‐MeATP (1 × 10−6 m).
The results show that, in the rat annococcygeus muscle, (1) field or extrinsic nerve stimulation released only one excitatory transmitter, namely NA, although receptors for both NA and ATP were present on the muscle, (2) α, β‐MeATP was selective for purinoceptors and (3) there was no evidence for excitatory co‐transmission in this tissue.
The effects of external and internal application of disopyramide on the ionic currents of the squid giant axon
Authors: Elliott J.R. , Hendry B.M. 
Published: July 2012

The actions of the class I anti‐arrythmic agent, disopyramide, on the ionic currents of the voltage‐clamped squid axon have been investigated, by use of both extra‐axonal and intra‐axonal routes of application.
Extra‐axonal application of 0.1 mm disopyramide produced no significant effects on the membrane currents. External disopyramide at 1.0 mm caused small, poorly reversible inhibition of both sodium and potassium currents. This block was use‐dependent and was enhanced by use of test stimuli to more positive membrane potentials.
Intra‐axonal application of 0.1 mm disopyramide caused a 40% reduction in the first‐pulse sodium current (tonic block) and an additional use‐dependent block. Analysis of first‐pulse currents in terms of the Hodgkin‐Huxley formalism indicated that the block resulted mainly from a reduction in the maximum available sodium conductance (gNa); there were no effects on the voltage dependence of the steady‐state activation and inactivation parameters, m∞ and h∞.
The use‐dependent actions of disopyramide were investigated with a double voltage‐clamp pulse protocol. The significant use‐dependent effects of the drug were a further reduction in gNa and an increase in the time constant of inactivation (∞h).
Disopyramide appears to enter a blocking site in the sodium channel which is only readily accessible from the axoplasmic phase. Partition to the site depends on membrane voltage and on the state of the channel gates. Disopyramide binds at a significant rate to both open and inactivated forms of the sodium channel.
Postjunctional α2‐adrenoceptors mediate venoconstriction in the hindquarters circulation of anaesthetized cats
Authors: Bentley Geoffrey A. , Widdop Robert E. 
Published: July 2012

A study was made of the subtypes of postjunctional α‐adrenoceptors which mediate arterial and venous constriction in the hindquarters circulation of anaesthetized cats, as measured by changes in perfusion pressure and vena cava blood flow, respectively.
It was found that, while noradrenaline caused constriction in both the arterial and venous compartments, methoxamine caused only arterial constriction. Clonidine and B‐HT 920 also caused arterial and venous constriction although autodesensitization to both drugs occurred.
The ability of either prazosin or yohimbine to antagonize the constrictor effects of noradrenaline was also examined. It was found that the combination of both antagonist drugs abolished both the arterial and venous constrictor effects of noradrenaline. However, there was a greater prazosin‐resistant response to noradrenaline in the venous compartment as compared with the arterial effects of noradrenaline. Yohimbine caused approximately equal reductions in the effect of noradrenaline in both arteries and veins, which was greater than that observed with prazosin.
These results suggest that, in the cat hindquarters, both α1‐ and α2‐adrenoceptors are present in the arterial circulation, whereas there are mainly α2‐adrenoceptors in the venous circulation.
Inhibitors of prostaglandin dehydrogenase (Ph CL 28A and Ph CK 61A) increase output of prostaglandins from rat isolated lung
Authors: Bakhle Y.S. , Pankhania J.J. 
Published: July 2012

Two potent inhibitors of prostaglandin dehydrogenase (PGDH), Ph CL 28A and Ph CK 61A, have been investigated for their effects on prostaglandin catabolism and synthesis in rat isolated lung.
Both CL 28A (0.3 μm) and CK 61A (0.5 and 5 μm) markedly increased the survival of prostaglandin E2 (PGE2) and PGF2α on a single passage through the pulmonary circulation.
Both inhibitors delayed the efflux of 14C following injection of [14C]‐PGE2 through the pulmonary circulation.
Output of PGE2 and PGF2α but not that of 6‐oxo‐PGF1α from exogenous arachidonic acid (AA) was increased by CL 28A.
Output of all three prostaglandins from endogenous AA stimulated by calcium ionophore A23187 was increased by CL 28A.
With CK 61A, output of 6‐oxo‐PGF1α from exogenous AA was not increased but that from endogenous AA was increased by either concentration of this inhibitor.
We conclude that it is possible to increase output of biologically active prostaglandins from lung by preventing their inactivation in situ.
The apparent selectivity of PGI2 synthesis from endogenous AA to potentiation by the inhibitors may have therapeutic possibilities.
α2‐Adrenoceptor blockade prevents cardiac glycoside‐evoked neurotransmitter release from sympathetic nerves in dog saphenous vein
Authors: Powis D.A. 
Published: July 2012

The effect of α‐adrenoceptor antagonists upon neurotransmitter release evoked by cardiac glycosides from sympathetic nerve terminals has been investigated in dog saphenous vein.
In rings of saphenous vein preloaded with [3H]‐noradrenaline, acetylstrophanthidin (ACS) caused a concentration‐dependent efflux of 3H (EC50 ca. 4.4 μm) that was attenuated by phentolamine and yohimbine but not by prazosin.
In helical strips of saphenous vein superfused with ACS at EC50 the efflux of 3H‐compounds in general, and of [3H]‐noradrenaline in particular, occurred after a short delay and increased with time to a maximum reached at 75 min. Phentolamine and phenoxybenzamine, but not prazosin reduced the efflux of [3H]‐noradrenaline and of total 3H‐compounds throughout the time‐course of the ACS‐evoked effect.
In helical strips of saphenous vein the glycoside ouabain also caused an increase in [3H]‐noradrenaline and in total 3H‐efflux that was attenuated by phentolamine.
By contrast with the above, in bovine adrenal medullary chromaffin cells, which appear to have no functional α‐adrenoceptors, ACS caused a small, but significant increase in 3H‐efflux which was not prevented by phentolamine.
Phentolamine, at concentrations that attenuate markedly the ouabain‐or ACS‐evoked increase in 3H‐efflux from dog saphenous vein, did not cause significant inhibition of cocaine‐sensitive [3H]‐noradrenaline uptake nor did it reduce the extent of the 3H‐efflux evoked either by tyramine or by reduced extracellular Na+. These findings imply that phentolamine does not affect ACS‐evoked neurotransmitter release by an action on the catecholamine uptake mechanism.
It is concluded that the cardiac glycoside‐evoked increase in neurotransmitter release from noradrenergic nerve terminals of dog saphenous vein is modulated by a mechanism that involves an α2‐adrenoceptor.
Selective inhibition by gossypol of endothelium‐dependent relaxations augments relaxations to glyceryl trinitrate in rabbit coeliac artery
Authors: Alheid Ute , Dudel Christian , Förstermann Ulrich 
Published: July 2012

Acetylcholine, substance P, prostaglandin E, and the nitrovasodilator glyceryl trinitrate induced concentration‐dependent relaxations of endothelium‐intact strips of rabbit coeliac artery precontracted with noradrenaline.
Endothelium‐denuded strip preparations contracted to acetylcholine and showed no response to substance P. The relaxant response to prostaglandin E1 was unimpaired after removal of endothelium, whereas the response to glyceryl trinitrate was increased.
A 20 min exposure of endothelium‐intact strips to gossypol, an irreversible inhibitor of the production and/or release of endothelium‐derived relaxing factor, abolished vasodilatation in response to the endothelium‐dependent agents acetylcholine and substance P, did not change relaxations to prostaglandin E1, but significantly enhanced relaxations in response to glyceryl trinitrate.
In view of the assumed common mechanism of action of endothelium‐derived relaxing factor and nitrovasodilators, these results suggest an interference of the two active principles at the level of the vascular smooth muscle cell.
Lack of evidence for increased descending inhibition on the dorsal horn of the rat following periaqueductal grey morphine microinjections
Authors: Dickenson Anthony H. , Le Bars Daniel 
Published: July 2012

Recordings were made from 18 neurones in the dorsal horn of the rat, anaesthetized with halothane. All cells received A‐and C‐fibre inputs and responded to innocuous and noxious stimuli applied to their excitatory receptive fields located on the extremity of the ipsilateral hindpaw. Transcutaneous application of suprathreshold (mean 3.2T) 2 ms square‐wave pulses to the centre of the receptive fields resulted in responses to A‐and C‐fibre activation being observed; a mean 32.4 ± 6.0 C‐fibre latency spikes were evoked per stimulus.
A high dose (20 μg) of morphine in 0.5 μl sterile saline, microinjected into the periaqueductal grey matter (PAG) had no effect on the C‐fibre‐evoked activity of thirteen cells (72%) and facilitated 5 neurones (28%). Microinjection sites covered most of the PAG particularly the caudal medioventral zone.
A relatively high dose (6 mg kg−1, i.v.) of systemic morphine chloride, sufficient to elicit the direct spinal action of the opiate, inhibited all 5 cells tested.
We conclude that there is little evidence that the supraspinal action of morphine includes increased descending controls and depression of dorsal horn neurones in the rat.
[Met5]enkephalin acts via δ‐opioid receptors to inhibit pelvic nerve‐evoked contractions of cat distal colon
Authors: Kennedy Charles , Krier Jacob 
Published: July 2012

The effects of opioids on the sacral parasympathetic outflow to cat distal colon were studied in vitro using muscle strips orientated in the axis of the longitudinal muscle layer, with pelvic nerves attached. Electrical stimulation of the pelvic nerves evoked contractions that were blocked by atropine (1 × 10−6 m) and tetrodotoxin (3 × 10−7 m).
[d‐Pen2, d‐Pen5]enkephalin and [Met5]‐ and [Leu5]enkephalin caused concentration‐dependent, reversible inhibition of pelvic nerve‐evoked contractions, with IC50 values of 8.3 × 10−10 m, 2.2 × 10−9 m and 2.1 × 10−9 m respectively.
Morphine (1 × 10−7‐1 × 10−5 m) and [d‐Ala2, MePhe4, Gly‐ol5]enkephalin (1 × 10−8‐1 × 10−6 m) and U‐50,488H (1 × 10−8‐1 × 10−6 m) were much less potent as inhibitors than [Met5]‐ or [Leu5]enke‐phalin.
Naloxone (1 × 10−7 m), an antagonist at each of the three opioid receptor types, antagonized the effects of both [Met5]enkephalin and morphine. However, ICI 174,864, a specific δ‐opioid receptor antagonist, antagonised the effects of [Met5]enkephalin only.
The inhibitory actions of [Met5]enkephalin were inversely related to frequency of pelvic nerve stimulation. Also, [Met5]enkephalin at a concentration (3 × 10−9 m) which produced a large inhibition of neurogenic contractions, had no effect on contractions to exogenous acetylcholine. These results suggest a prejunctional site for inhibitory opioid receptors.
In summary, prejunctional inhibitory δ‐opioid receptors are present on the sacral parasympathetic outflow to cat distal colon; κ‐and/or μ‐opioid receptors may also be present, but appear to be of lesser importance.
Renal vascular effects of leukotriene C4 in the isolated perfused kidney of the rat
Authors: Frölich Jürgen C. , Yoshizawa Mamoru 
Published: July 2012

The vascular effects of leukotriene C4 (LTC4) were investigated in the isolated perfused kidney of the rat.
LTC4 (6.4 × 10−10 to 3.2 × 10−8 mol kg−1 min−1 given over 5 min) resulted in a prompt, dose‐dependent increase in renal vascular resistance in a recirculating system, which lasted for more than 60 min.
LTC4 was 10 to 20 fold and 1000 to 2000 fold, respectively, less active on a molar basis than noradrenaline and angiotensin II in eliciting renal vasoconstriction.
The vascular response to LTC4 was blocked dose‐dependently by FPL 55712, an antagonist of slow reacting substance of anaphylaxis. OKY 1581, a specific thromboxane synthetase inhibitor, and indomethacin, a cyclo‐oxygenase inhibitor, did not influence the LTC4 response.
LTC4 given in a single‐pass perfusion system resulted in a short lasting response with baseline values for renal vascular resistance reached after 4 min.
These results show that LTC4 is a short acting renal vasoconstrictor with less potency than noradrenaline and angiotensin II. Its pressor effects seem to be mediated by specific leukotriene receptors and independent of cyclo‐oxygenase products. The long‐lasting effect in the recirculating arrangement, in contrast to the single pass system, is compatible with formation of active metabolite(s).
Evidence that 8‐hydroxy‐2‐(n‐dipropylamino)tetralin (8‐OH‐DPAT) is a selective α2‐adrenoceptor antagonist on guinea‐pig submucous neurones
Authors: Crist J. , Surprenant Annmarie 
Published: July 2012

Intracellular recordings were made from neurones of the submucous plexus and from submucosal arteriolar smooth muscle of the guinea‐pig ileum for the purpose of examining the actions of 8‐hydroxy‐2‐(n‐dipropylamino)tetralin (8‐OH‐DPAT).
8‐OH‐DPAT (10 nm‐20 μm) had no direct presynaptic or postsynaptic actions on submucous plexus neurones.
Membrane hyperpolarizations induced in neurones by noradrenaline or UK 14304 were competitively antagonized by 8‐OH‐DPAT. For dose‐ratios up to 40, Schild plots were linear with slopes not significantly different from unity; pA2 values for the 8‐OH‐DPAT antagonism of postsynaptic α2‐adrenoceptors were 6.9‐7.2.
The inhibitory synaptic potential, which is due to activation of α2‐adrenoceptors located on submucous plexus neurones, was selectively inhibited by 8‐OH‐DPAT; the IC50 value for inhibition of the inhibitory synaptic potential was 250 nm.
Neuronal hyperpolarizations mediated through activation of δ‐opioid receptors or somatostatin receptors were unaffected by 8‐OH‐DPAT (0.1–1 μm).
The ability of noradrenaline and UK 14304 to inhibit the release of acetylcholine at synapses in the submucous plexus, and to inhibit the release of the transmitter which mediates the excitatory junction potential in the submucosal arteriolar smooth muscle, was also blocked by 8‐OH‐DPAT.
These results suggest that some of the actions of 8‐OH‐DPAT previously ascribed to agonism at 5‐hydroxytryptamine (5‐HT)1 receptors may actually result from blockade of the actions of endogenously released noradrenaline acting on α2‐adrenoceptors.
Increased GABAB receptor function in mouse frontal cortex after repeated administration of antidepressant drugs or electroconvulsive shocks
Authors: Gray Julian A. , Green A. Richard 
Published: July 2012

Addition of baclofen to a medium containing slices of mouse frontal cortex inhibited the potassium‐evoked release of 5‐hydroxytryptamine (5‐HT) in a concentration‐dependent manner. The degree of inhibition was increased in frontal cortex tissue taken from animals treated for 14 days with amitriptyline (10 mg kg−1, twice daily) at all concentrations of baclofen tested (10−6 m − 10−4 m).
Administration of either desipramine, mianserin or zimeldine (10 mg kg−1 daily) for 14 days also approximately doubled the degree of inhibition evoked by addition of baclofen (10−5 m) to the medium.
One day of treatment with the antidepressant drugs did not alter the inhibitory effect of baclofen on K+‐evoked 5‐HT release.
Addition of the antidepressant drugs to the medium had no effect on the K+‐evoked release of 5‐HT.
Repeated administration of electroconvulsive shock (5 seizures spread out over 10 days), like amitriptyline, produced a significant enhancement of the baclofen‐induced inhibition of 5‐HT release over the range of baclofen concentrations studied. A single electroconvulsive shock had no effect.
These data suggest that repeated administration of the antidepressant drugs or electroconvulsive shock increases the function of the γ‐aminobutyric acid (GABA)B receptor in the frontal cortex modulating 5‐HT release and are consistent with the finding of increased GABAB receptor number in this region following various antidepressant treatments.
δ‐Opioid receptors mediate inhibition of fast excitatory postsynaptic potentials in cat parasympathetic colonic ganglia
Authors: Kennedy Charles , Krier Jacob 
Published: July 2012

The effects of opioids on synaptic transmission in cat sacral parasympathetic colonic ganglia were studied in vitro, using intracellular electrophysiological techniques. Electrical stimulation of the pelvic nerve evoked fast excitatory postsynaptic potentials (e.p.s.ps), which were blocked by hexamethonium and tetrodotoxin.
[d‐Pen2, d‐Pen5] enkephalin and [Met5]enkephalinamide, δ‐opioid receptor agonists, caused concentration‐dependent, reversible depression of fast e.p.s.ps, but had no effect on depolarizations evoked by pressure ejection of the nicotinic agonist 1,1‐dimethyl‐4‐phenyl‐piperazinium. Cell transmembrane potential and membrane input resistance were also unaffected.
U‐50,488H, a κ‐opioid receptor agonist, had a very small depressant action while [d‐Ala2, MePhe4, Gly‐ol5] enkephalin, a μ‐opioid receptor agonist, had no effect on fast e.p.s.p. amplitude. Neither compound affected cell transmembrane potential or membrane input resistance.
The inhibitory actions of [d‐Pen2, d‐Pen5] enkephalin were antagonized by both naloxone, an antagonist at each of the three opioid receptor types, and by ICI 174,864, an antagonist selective for δ‐opioid receptors.
Naloxone and ICI 174,864 both also potentiated fast e.p.s.p. amplitude per se in 50% of cells tested.
It is concluded that exogenous opioids act at presynaptic δ‐opioid receptors to inhibit sacral parasympathetic synaptic transmission in cat colonic ganglia in vitro. Furthermore, the effects of opioid anatagonists alone, suggest that endogenous opioids may also be released by preganglionic nerve stimulation and so regulate the release of acetylcholine in these ganglia.
Positive inotropic effects of histamine in anaesthetized dogs
Authors: Einstein Rosemarie , Mihailidou Anastasia S. , Richardson Desmond P. 
Published: July 2012

The cardiovascular effects of histamine were examined in dogs anaesthetized with pentobarbitone
The effect of histamine on heart rate, blood pressure, left ventricular pressure, dP/dtmax and dP/dt: IIT (integrated isometric tension) was compared in the presence and absence of autonomic reflexes and blood pressure control.
In innervated animals with no attempt to control blood pressure, histamine produced dose‐dependent decreases in blood pressure and heart rate and either positive or negative inotropic actions.
When autonomic reflexes were abolished, this variability in inotropic response was reduced and histamine produced a slight positive inotropic response. There was a decrease in blood pressure and a positive chronotropic response to histamine.
When blood pressure was controlled and the cardiac nerves were intact, histamine produced a decrease in heart rate. However, in the denervated animals, there was a slight increase in heart rate.
Inotropic responses to histamine in the blood pressure controlled groups were less variable than when blood pressure was uncontrolled. In all of these animals there was an increase in contractility, the increase being more marked in the denervated group.
The H2‐receptor agonist impromidine produced a positive inotropic action in intact animals with uncontrolled blood pressure.
Capsaicin enhances the non‐adrenergic twitch response of rat vas deferens
Authors: Moritoki Hideki , Iwamoto Takeshi , Kanaya Jun , Ishida Yukio , Ando Kenshi , Kitagawa Kouki 
Published: July 2012

Capsaicin (Cap) enhanced the twitch response of the epididymal and prostatic portions of rat vas deferens induced by field stimulation at 0.1 Hz. The effect of Cap was reproducible and showed no desensitization.
Prazosin, and pretreatment with reserpine or Cap did not affect the potentiating effect of Cap, whereas pretreatment with 6‐hydroxydopamine abolished the action of Cap.
Cap tended to attenuate the contractions induced by noradrenaline, tyramine and ATP.
Like Cap, substance K and substance P augmented the twitch response without causing desensitization, but their effects differed somewhat from that of Cap. Calcitonin gene‐related peptide inhibited the twitch response.
These results suggest that Cap enhances a stimulation‐induced, prazosin‐resistant non‐adrenergic twitch response of rat vas deferens through an as yet undefined prejunctional mechanism. This mechanism is possibly mediated by some peptide released in response to Cap from sensory neurones, which in turn acts on sympathetic nerves and increases stimulation‐induced release of a mediator or co‐transmitter responsible for the non‐adrenergic twitch response. However, the possibility that Cap has a direct action on sympathetic nerves cannot be ruled out.