bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential blocking actions of idazoxan against the inhibitory effects of 6‐fluoronoradrenaline and clonidine in the rat vas deferens
Authors: Hicks P.E. , Langer S.Z. , Macrae A.D. 
Published: July 2012

The prejunctional inhibitory effects of clonidine and 6‐fluoronoradrenaline (6‐FNA) have been evaluated in the isolated prostatic segment of the rat vas deferens, against the twitch response evoked by low frequency (0.1 Hz) field stimulation.
The inhibitory potency of 6FNA was significantly increased in the presence of cocaine (1 μM) or pargyline (10 μM), but was not modified in the vas deferens from rats pretreated with reserpine when the endogenous levels of noradrenaline (NA) were decreased by 97%. Clonidine was significantly more potent than 6‐FNA as an inhibitory agonist, and the potency of clonidine was not modified after cocaine, pargyline or reserpine.
The α2‐adrenoceptor blocking agent idazoxan, was a competitive antagonist against the inhibitory effects of clonidine under all experimental conditions. In contrast, the only antagonism shown by idazoxan against the inhibitory effects of 6‐FNA was in the presence of cocaine (1 μM), and this antagonist effect of idazoxan was not concentration‐related.
Low concentrations of 6‐FNA caused concentration‐dependent facilitatory effects on the twitch response, which were significantly greater after treatment with idazoxan (1 μM) in reserpine‐treated vas deferens. These facilitatory effects of 6‐FNA were always observed in the presence of prazosin (300 nM) and also after treatment of the preparations with phenoxybenzamine (10 μM), a concentration which abolished the inhibitory actions of both clonidine and 6‐FNA. The facilitatory effects on the twitch response induced by low concentrations of 6‐FNA are therefore unlikely to be due to either α1‐ or α2‐adrenoceptor stimulation.
In conclusion, the failure of idazoxan to block the inhibitory effects of 6‐FNA, while exerting a potent competitive antagonism of clonidine‐induced inhibitory effects, supports the proposal that α2‐adrenoceptors may in fact be subdivided into two subclasses, involving imidazoline and phenylethylamine recognition sites.
The 5‐HT1 receptor agonist RU‐24969 decreases 5‐hydroxytryptamine (5‐HT) release and metabolism in the rat frontal cortex in vitro and in vivo
Authors: Brazell M.P. , Marsden C.A. , Nisbet A.P. , Routledge C. 
Published: July 2012

K+‐stimulated release of [3H]‐5‐hydroxytryptamine ([3H]‐5‐HT) from rat frontal cortex slices was decreased by the 5‐HT receptor agonists 5‐methoxy‐n1N‐dimethyltryptamine and 5‐methoxy‐3(1,2,3,6,‐tetrahydro‐4‐pyrindinyl)‐1H‐indole (RU‐24969) (1 × 10−5 M).
RU‐24969 (10 mg kg−1, i.p.) decreased extracellular 5‐HT and its metabolite 5‐hydroxyindoleacetic acid measured in vivo by use of intracerebral dialysis combined with high performance liquid chromatography and electrochemical detection.
The decrease in extracellular 5‐hydroxyindoleacetic acid in vivo after RU‐24969 (10 mg kg−1, i.p.) was also observed by in vivo voltammetry.
The non‐selective 5‐HT antagonist metergoline prevented the RU‐24969‐induced decrease in 5‐HT release and metabolism in vivo while the 5‐HT2 receptor antagonist R‐55669 (ritanserin) did not.
The results support the view that RU‐24969 stimulates a 5‐HT1 receptor that is involved in the autoregulation of 5‐HT release and metabolism.
Electrophysiological analysis of the nature of adrenoceptors in the rat basilar artery during development
Authors: Byrne N.G. , Hirst G.D.S. , Large W.A. 
Published: July 2012

The nature of adrenoceptors in basilar arteries of neonatal rats was investigated by means of electrophysiological techniques.
In immature (2–6 day postnatal) rats, micro‐injection of noradrenaline elicited a depolarization which consisted of two components. The initial ‘fast’ component (time to peak of 0.3–4 s) was slightly reduced by phentolamine and was not antagonized by propranolol. The second ‘slow’ component (time to peak of about 50 s) was not blocked by phentolamine but was antagonized by low concentrations (10−7 M) of propranolol.
In immature rats, micro‐injection of isoprenaline was more potent than noradrenaline in evoking the ‘slow’ depolarization but less effective in eliciting the ‘fast’ response. The pharmacology with respect to adrenoceptor antagonists of both components of the isoprenaline‐ and noradrenaline‐induced depolarizations was similar. There was some evidence of inhibitory β‐adrenoceptors in immature rat basilar vessels.
In adult rats (6 week old) noradrenaline produced a large ‘fast’ depolarization which was followed by a ‘slow’ tail response. Both components were not antagonized by phentolamine or propranolol.
It appears that in the basilar artery of neonatal rats there are excitatory α‐ and inhibitory β‐adrenoceptors but the major responses to noradrenaline and isoprenaline are mediated by γ‐ and excitatory β‐receptors. In adult animals the γ‐adrenoceptor predominates.
Experiments were carried out in which agonists were applied by ionophoresis. These results confirm the presence of excitatory β‐receptors in neonatal basilar vessels and show the response has slow kinetics and it is likely that the β‐receptors are distributed uniformly over the smooth muscle surface. In adult animals it was not possible to elicit an excitatory β‐receptor‐mediated response.
The ionophoretic application of noradrenaline never evoked a perceptible depolarization which could be attributed to γ‐adrenoceptor stimulation. This result is discussed in terms of receptor distribution with respect to synaptic function in a syncytium.
Effects of a combination of metoprolol and dazmegrel on myocardial infarct size in rats
Authors: Bullock Gillian R. , Leprán Istvan , Parratt James R. , Szekeres Laszlo , Wainwright Cherry L. 
Published: July 2012

The effects of acute pretreatment with metoprolol, dazmegrel and a combination of these two drugs has been examined on myocardial infarct size in rats. Ischaemic damage was assessed 4 h after coronary artery occlusion in anaesthetized rats and after 48 h of ischaemia in conscious rats. Infarct size was measured histochemically (by using periodic‐acid‐Schiff diastase reaction for glycogen) and by standard histological examination (haematoxylin and eosin stain).
There was some evidence of protection of the myocardium by metoprolol following 4 h of ischaemia (determined histologically) but this was not apparent 48 h after occlusion.
When given alone, dazmegrel had no significant effects on infarct size assessed by either method. A clear reduction in the extent of glycogen depletion and histological damage was observed with the combination of metoprolol and dazmegrel 48 h after the onset of ischaemia. This protection was seen to occur in the horizontal plane of the heart, preventing the extension of the infarct towards the posterior wall of the left ventricle and showing some salvage of the epicardial surfaces.
The effects of Anemonia sulcata toxin II on vertebrate skeletal muscle
Authors: Harris John B. , Pollard Sandra , Tesseraux Irene 
Published: July 2012

Some effects of the sea anemone toxin, ATX‐II, on vertebrate skeletal muscle have been described.
At a concentration of 1 × 10−7 ‐ 1 × 10−6 M, ATX‐II caused a sodium‐dependent depolarizaton of the muscle fibres of the rat soleus and extensor digitorum longus, of the mouse soleus and extensor digitorum longus and of the chicken posterior latissimus dorsi. The muscle fibres of the frog sartorius were insensitive to the toxin.
Action potentials generated by direct stimulation were prolonged by ATX‐II, but the degree of prolongation was variable. Chicken posterior latissimus dorsi muscle fibres were most sensitive in this regard, and mouse extensor digitorum longus were least sensitive.
Both denervated and immature muscle fibres were more sensitive to ATX‐II than mature innervated muscle fibres. The sensitivity to ATX‐II declined rapidly as muscle fibres matured.
In some muscles, the prolongation of the action potential was enhanced by repetitive stimulation, but not by the passive depolarization or hyperpolarization of the muscle fibres.
The actions of ATX‐II could be reversed by washing in all but the innervated soleus of the mature rat.
The effect of reserpine treatment on the extraneuronal uptake of [3H]‐isoprenaline into rat atria
Authors: Morton A.J. 
Published: July 2012

Treatment of rats with reserpine (1 mg kg−1 day−1) for up to 7 days resulted in a marked decrease in a corticosterone‐sensitive component of the extraneuronal accumulation of [3H]‐isoprenaline into their atria.
The change in extraneuronal uptake did not appear to be due to a direct action of reserpine on the uptake mechanism, since it was several days before the treatment had a significant effect on the accumulation of [3H]‐isoprenaline. Further, reserpine in vitro did not inhibit extraneuronal uptake.
The reserpine‐induced change in the accumulation of [3H]‐isoprenaline was not an artifact due to changes in water balance, ion distribution, extracellular space or tissue atrophy. Nor was the change due to an increase in the efflux of [3H]‐isoprenaline from the tissue.
These experiments support the suggestion that the extraneuronal uptake is dependent upon a functional adrenergic innervation.
Inflammatory oedema induced by synergism between calcitonin gene‐related peptide (CGRP) and mediators of increased vascular permeability
Authors: Brain S.D. , Williams T.J. 
Published: July 2012

The potent vasodilator calcitonin gene‐related peptide (CGRP, human synthetic), when mixed with histamine and injected intradermally in the rabbit, induced a marked potentiation of local oedema.
CGRP also potentiated oedema induced by other mediators of increased microvascular permeability in the rabbit; bradykinin, platelet‐activating factor (Paf), C5a des Arg, N‐formylmethionyl‐leucyl‐phenylalanine (FMLP) and leukotriene B4 (LTB4).
Substance P alone, or mixtures of substance P and CGRP, failed to induce oedema in rabbit skin. In rat skin, however, substance P induced oedema and this was potentiated by CGRP.
CGRP had a protracted potentiating action following intradermal injection in the rabbit. The time for half loss of activity for CGRP was 40.1 ± 7.5 min compared to 18 ± 1 min for prostaglandin E2 (PGE2).
No loss of potentiating activity was detected after incubation of CGRP in rabbit plasma or blood for 60 min.
We postulate that endogenous CGRP, if released locally from nerve endings, could have a marked enhancing effect on oedema induced by other mediators in an inflammatory reaction.
Effect of some monoamine oxidase inhibitors on the thiamin status of rabbits
Authors: Ali B.H. 
Published: July 2012

The monamine oxidase (MAO) inhibitors harmaline, tranylcypromine, deprenyl, clorgyline and iproniazid were injected intraperitoneally for five days to rabbits at doses that produced significant MAO inhibition. The first three inhibitors raised the concentrations of pyruvate and lactate in blood, decreased the activity of erythrocyte transketolase (TK) and increased the thiamin pyrophosphate (TPP) effect. The drugs also produced anorexia and loss of body weight. The changes were suggestive of an adverse effect on the thiamin status. Clorgyline and iproniazid, however, raised the blood concentrations of pyruvate and lactate but did not affect significantly erythrocyte TK activity or TPP effect.
Treatment of rabbits for 14 days with the thiamin antagonists pyrithiamin (20 μg kg−1) or oxythiamin (0.8 mg kg−1) produced a significant drop in TK activity and increase in the lactate and pyruvate concentrations as well as an increase in TPP effect. Pyrithiamin (5, 10 or 20 μg kg−1, 14 days) lowered significantly the activity of MAO in the liver and brain of rabbits. Treatment with the other antagonist, oxythiamin, at doses of 0.2 or 0.4 mg kg−1 for 14 days had no significant effect on MAO activity. At a dose of 0.8 mg kg−1 a significant drop in MAO activity occurred.
A pair‐feeding trial indicated that the biochemical changes produced in animals treated with MAO inhibitors were attributable to the drugs per se, and not to the ensuing anorexia.
Thiamin (100 μg kg−1, subcutaneously) when given concomitantly with pyrithiamin, oxythiamin, harmaline, deprenyl and tranylcypromine was effective in preventing the development of thiamin deficiency.
[14C]‐β‐phenethylamine, its distribution after administration by various routes to cats, and the effects of monoamine oxidase inhibitors
Authors: Garcha G. , Imrie P.R. , Marley E. , Thomas D.V. 
Published: July 2012

[14C]‐β‐phenethylamine ([14C]‐PEA) was instilled intragastrically, intraduodenally (i.d.) or infused into the portal vein or femoral artery of cats, anaesthetized with chloralose, to investigate its distribution in the body.
[14C]‐PEA and phenylacetic acid (PAA) accounted for approximately 85% of radioactivity recovered in blood from control cats or those pretreated with deprenyl or mebanazine. Progressively greater portal venous (PV), cranial mesenteric arterial (CMA) and PV‐CMA concentrations of PEA and PAA were observed with increase in amount of PEA instilled intraduodenally (i.d.); PAA predominated over PEA, more so in CMA than PV blood. Radioactivity was not recovered from blood following intragastric instillation of PEA.
When histamine 1.7 μmol kg−1, i.d., was combined with PEA 1.7 μmol kg−1, i.d., or tyramine 8.5 μmol kg−1, i.d., was combined with PEA 8.5 μmol kg−1, i.d., PV‐CMA values for PEA were significantly augmented.
Arterial concentrations of PEA were increased 3.5 to 5 fold compared to controls by pretreatment with mebanazine or deprenyl plus clorgyline; arterial concentrations of PAA were reduced. PEA blood concentrations were not significantly altered by clorgyline or deprenyl pretreatment.
Infusion of PEA 680, 1020 or 1360 nmol kg−1 min−1 for 20 min into the portal vein raised blood pressure 60 to 100 mmHg (at a PEA concentration of ca, 2 nmol ml−1) but lacked effect on the nictitating membrane despite peak arterial PEA concentrations of 20 nmol ml−1; in cats pretreated with mebanazine or clorgyline plus deprenyl, half‐maximum contraction of the nictitating membrane occurred with arterial PEA concentrations of 4.8 to 9 nmol ml−1. In cats pretreated with mebanazine or deprenyl plus clorgyline, half maximum contraction of the nictitating membrane was elicited also by intraduodenal PEA 8.5 μmol kg−1 at arterial PEA concentrations of ca. 2 nmol ml−1, despite lack of effect of PEA 17 μmol kg−1, i.d., in control cats with a peak arterial PEA concentration of 1.8 nmol ml−1.
[14C]‐PEA and PAA were recovered from liver, kidney, distal small intestine, lung, arterial vessel walls, skeletal muscle, brain, foetus and amniotic liquor, after PEA instilled i.d., overall concentration of PEA exceeding that of PAA except in the kidney. The combined amount of PEA and PAA in kidney was 7 to 20 fold that in other tissues. PEA content of tissues was significantly elevated and that of PAA diminished by pretreatment with deprenyl plus clorgyline, and to a lesser extent after mebanazine.
Involvement of enteric neurones in the response of guinea‐pig ileum preparations to metoclopramide
Authors: Bou J. , Fernández A.G. , Jauregui J.M. , Massingham R. 
Published: July 2012

The role of myenteric neurones in mediating the stimulant effects of metoclopramide in vitro in the guinea‐pig ileum has been investigated using the non‐ionic surfactant Triton X‐100.
Histological examination of the ileum 30 days after application of Triton X‐100 to the serosal surface demonstrated a marked reduction in the number of ganglion cells and nerve elements in the myenteric plexus.
Longitudinal muscle‐myenteric plexus (LM‐MP) preparations from Triton X‐100‐treated animals were unresponsive to dimethylphenylpiperazinium and responded poorly or not at all to electrical field stimulation.
Metoclopramide (30 μM) elicited small contractions in LM‐MP preparations from control and sham‐operated animals but failed to contract Triton X‐100‐treated tissues. However, tissues responded in a similar manner to exogenous acetylcholine (ACh).
These results demonstrate the importance of a prejunctional site of action for metoclopramide in this tissue and suggest that contractile responses to the drug are mediated indirectly, probably by increased release of ACh from myenteric neurones.
Effect of apamin on responses to BRL 34915, nicorandil and other relaxants in the guinea‐pig taenia caeci
Authors: Weir Sheila W. , Weston A.H. 
Published: July 2012

BRL 34915 (4–64 × 10−7 M), isoprenaline (0.5–32 × 10−8 M) and nicorandil (4–64 × 10−6 M) produced a slowly‐developing relaxation of spontaneous tone of the guinea‐pig taenia caeci; with no after‐contraction on washout. These inhibitory responses were unaffected by apamin (10−7 M).
Adenosine triphosphate (0.06‐2 × 10−3 M) and noradrenaline (1–16 × 10−7 M) produced a rapid inhibition of spontaneous tone with a prominent after‐contraction, especially on washout. Both the inhibitory effect and the rebound contraction were abolished by apamin (10−7 M).
Exposure to both BRL 34915 (64 × 10−7 M) and to nicorandil (64 × 10−6 M) produced an increase in the 86Rb efflux rate coefficient which was unaffected by apamin (10−7 M).
Exposure to isoprenaline (32 × 10−8 M) had no effect on the 86Rb efflux rate coefficient.
Exposure to noradrenaline (16 × 10−7 M) produced an increase in the 86Rb efflux rate coefficient which was abolished by apamin (10−7 M).
The results confirm that both BRL 34915 and nicorandil are capable of opening potassium channels in smooth muscle but show that the channel is not apamin‐sensitive.
A protective effect of sulphinpyrazone against coronary occlusion‐induced shortening of myocardial refractory periods in the rat
Authors: Northover B.J. 
Published: July 2012

The hearts of anaesthetized, artificially ventilated rats were exposed, and the left coronary artery occluded. The diastolic threshold voltage for stimulation (DTV), the duration of the bipolar electrogram (DBE) and the functional refractory period (FRP) of the ischaemic area were measured at minute intervals for an hour after occlusion.
Coronary occlusion caused a rise in DTV, a prolongation of the DBE and a biphasic change in the FRP, with an initial prolongation phase (1–4 min) followed by a decline to below pre‐occlusion values (5–15 min).
Episodes of ventricular tachyarrhythmia (VT) were most frequent during the period 5–15 min after the onset of occlusion of the coronary artery. This coincided with the period when FRP was minimal and the difference between DBE and FRP was maximal.
Pretreatment of rats with sulphinpyrazone (2.5–40 mg kg−1) or indomethacin (5–20 mg kg−1) protected against the episodes of coronary occlusion‐induced VT and against the associated decline in FRP of the ischaemic muscle. Sulphinpyrazone was more effective than indomethacin in this respect and a combination of the two drugs was approximately as effective as sulphinpyrazone alone.
It was concluded that sulphinpyrazone protects rats against coronary occlusion‐induced episodes of VT by reducing the risk of ventricular action potential re‐entry. This effect is probably due to protection against the ischaemia‐induced shortening of the myocardial FRP.
An oxytocin receptor in anococcygeus muscles isolated from male mice
Authors: Gibson A. 
Published: July 2012

The nature of the neurohypophyseal peptide receptor in the anococcygeus muscles from male mice was investigated.
The rank order of potency of naturally occurring peptides was oxytocin > Arg‐vasotocin > Arg‐vasopressin>Lys‐vasopressin, which is similar to that found in the uterus and mammary gland.
Selective agonists on the oxytocin (OT) receptors of the uterus and mammary gland (Thr4‐OT; Gly7‐OT; Thr4‐Gly7‐OT) were also potent agonists in the mouse anococcygeus.
Competitive antagonists of uterine responses to oxytocin (dP‐TyrMe‐Thr4‐OT; dP‐TyrMe‐OT; dP‐Thr4‐OT; dp‐Orn8‐OT) were also competitive antagonists of oxytocin‐induced contractions of the mouse anococcygeus.
It is concluded that the neurohypophyseal peptide receptor of the male mouse anococcygeus is of the oxytocin type; antagonist pA2 values suggest that this receptor resembles, but may not be identical to, the uterine oxytocin receptor. Possible physiological and pharmacological implications of these observations are discussed.
Inhibition of calcium currents in cultured rat dorsal root ganglion neurones by (−)‐baclofen
Authors: Dolphin A.C. , Scott R.H. 
Published: July 2012

Voltage‐dependent inward calcium currents (ICa) activated in cultured rat dorsal root ganglion neurones were reversibly reduced in a dose‐dependent manner by (−)‐baclofen (10 μM to 100 μM).
Baclofen (100 μM) reduced the calcium‐dependent slow outward potassium current (IK(Ca)). This current was abolished in calcium‐free medium and by 300 μM cadmium chloride. The action of baclofen on IK(Ca) was reduced when the calcium concentration in the medium was increased from 5 mM to 30 mM.
The calcium independent fast transient voltage‐dependent outward current (IK(Vt)) was also reduced by baclofen; this effect remained present when Ca2+‐free medium was used to prevent contamination by IK(Ca).
4‐Aminopyridine (500 μM) reduced IK(Vt) and induced a small increase in ICa. The action of baclofen on ICa was partially antagonized by 4‐aminopyridine.
GABAB receptor‐mediated inhibition of ICa in cultured rat dorsal root ganglion neurones involves a direct mechanism rather than resulting indirectly from an increase in the residual outward potassium currents activated by depolarization. The reduction in ICa by baclofen was variable and dependent on the amplitude of control ICa, larger currents being more resistant to the baclofen‐induced inhibition.
Iloprost (ZK 36374) enhances recovery of regional myocardial function during reperfusion after coronary artery occlusion in the pig
Authors: van der Giessen W.J. , Schoutsen B. , Tijssen J.G.P. , Verdouw P.D. 
Published: July 2012

Ligation of the left anterior descending coronary artery in open‐chest pigs for 20 min caused a complete loss of regional myocardial function, which did not recover during the first two hours of reperfusion.
Infusion of the stable prostacyclin analogue Iloprost (100 ng kg−1 min−1) did not prevent the loss of systolic wall function during ischaemia.
Recovery of regional myocardial function during the first two hours of reperfusion was enhanced to 40% of baseline by Iloprost.
This effect of Iloprost cannot be explained by a decreased O2‐demand during ischaemia or an enhanced recovery of myocardial ATP content.
A study of the H2‐receptor for histamine stimulating adenylate cyclase in homogenates of guinea‐pig lung parenchyma
Authors: Foreman J.C. , Norris D.B. , Rising T.J. , Webber S.E. 
Published: July 2012

The effect of forskolin and several H2‐agonists was investigated on the activity of adenylate cyclase in homogenates of guinea‐pig lung parenchyma.
Histamine, 0.1 μM to 1 mM, dimaprit, 1 μM to 10 mM, 4‐methyl histamine, 0.1 μM to 10 mM, impromidine, 10 nM to 10μM and forskolin, 1 nM to 100 μM, all produced a dose‐dependent stimulation of adenylate cyclase activity above the basal level.
The histamine H1‐receptor antagonist mepyramine, 10 μM, and β‐adrenoceptor antagonist propranolol, 10 μM, had no effect on the stimulation by histamine of adenylate cyclase.
The dose‐response curve for stimulation by histamine of adenylate cyclase was shifted to the right in a dose‐dependent manner by increasing concentrations of several H2‐antagonists. Schild plots constructed for each H2‐antagonist produced straight lines with slopes not significantly different from unity. The equilibrium dissociation constants obtained for the H2‐antagonists in this study were similar to those previously reported for inhibition of dimaprit‐induced relaxation of the pre‐contracted lung strip, inhibition of [3H]‐tiotidine binding to homogenates of guinea‐pig lung parenchyma and inhibition of histamine‐stimulated adenylate cyclase in guinea‐pig gastric mucosa.