bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of idazoxan and other α2‐adrenoceptor antagonists on food and water intake in the rat
Authors: Jackson Helen C. , Griffin I.J. , Nutt D.J. 
Published: July 2012

Idazoxan (1, 3, 10 mg kg−1, i.p.) produced a significant increase in food and water intake in freely feeding rats during the daylight phase.
The more selective and specific α2‐adrenoceptor antagonists, RX811059 (0.3, 1, 3 mg kg−1, i.p.) and RX821002 (0.3, 1, 3 mg kg−1, i.p.), did not produce hyperphagia in rats, however, the highest dose produced a significant increase in water intake.
The peripherally acting α2‐adrenoceptor antagonist, L‐659,066 (1, 3, 10 mg kg−1, i.p.), did not affect food intake in the 4 h following injection, but the highest dose (10 mg kg−1), produced a large increase in water intake.
These results indicate that α2‐adrenoceptor antagonists may increase water intake by a peripherally mediated mechanism.
The lack of effect of RX811059 and RX821002 on food intake contrasts with the large dose‐related increases induced by idazoxan and suggests that the hyperphagic effects of idazoxan are not due to α2‐adrenoceptor blockade but may instead reflect its affinity for a non‐adrenoceptor site, a property not shared by the other α2‐antagonists.
Methylxanthine‐induced attenuation of pecking in chickens
Authors: Zarrindast M.R. , Nasir T. 
Published: July 2012

Apomorphine induced dose‐dependent pecking in chickens.
The response was decreased by theophylline or caffeine in a dose‐dependent manner.
Administration of theophylline or caffeine alone did not exert any effect on pecking behaviour.
Dipyridamole administration neither induced pecking nor altered the pecking induced by apomorphine.
Administration of 5‐N‐ethylcarboxamide‐adenosine to animals caused variable effects on pecking induced by apomorphine. The drug did not induce pecking by itself.
It is concluded that the inhibitory response to methylxanthines may be mediated through blockade of adenosine receptors. However, to prove this, more experiments are needed.
Effects of calcium modulators on vagally‐mediated constriction in the guinea‐pig isolated trachea
Authors: McCaig Dorothy J. , Aitken Susan 
Published: July 2012

The effects of calcium modulators on tracheal constriction evoked by vagal stimulation were examined in the isolated, innervated trachea of the guinea‐pig. Responses were assessed in the Krebs‐filled trachea as changes in intraluminal pressure (ILP), increases and decreases reflecting constriction and dilatation, respectively.
Preparations had a positive resting ILP, indicating significant spontaneous tone. Verapamil and nifedipine reduced baseline ILP, whilst Bay K 8644 had mixed effects.
Verapamil and nifedipine attenuated vagal responses in a concentration‐dependent manner. At lower concentrations attenuation was due entirely to postjunctional effects but at higher concentrations prejunctional effects may have contributed to attenuation.
Verapamil and nifedipine attenuated vagal responses in the absence or presence of flurbiprofen, indicating that their effects are largely independent of the generation of cyclo‐oxygenase products. Nifedipine, however, was less effective in reducing responses to low frequency vagal stimulation (up to 5 Hz) when flurbiprofen was present.
Bay K 8644 augmented vagal responses, the degree varying widely between preparations.
It was concluded that influx of Ca2+through voltage‐operated Ca2+channels contributes significantly to vagally‐mediated tracheal constriction in normal trachea and in trachea where endogenous release of cyclo‐oxygenase products is inhibited.
Clonidine inhibits ATP‐sensitive K+channels in mouse pancreatic β‐cells
Authors: Plant T.D. , Jonas J‐C. , Henquin J.C. 
Published: July 2012

The effects of clonidine and adrenaline on adenosine 5′‐triphosphate (ATP)‐sensitive K+channels were studied in pancreatic β‐cells from normal mice.
When perifused with a medium containing 1 mm glucose, many of the ATP‐sensitive K+channels in the β‐cell membrane are open. Under these conditions, clonidine (5–100 μm) reversibly decreased 86Rb efflux from the islets, whereas adrenaline was ineffective at concentrations up to 100 μm.
In 6 mm glucose, most of the ATP‐sensitive K+channels in the β‐cell membrane are closed. Opening these channels by diazoxide (100 μm) caused a marked acceleration of 86Rb efflux from the islets, which was attenuated by 100 μm clonidine.
ATP‐sensitive K+currents were measured in single β‐cells by the whole cell mode of the patch‐clamp technique. At concentrations above 4 μm, clonidine reversibly inhibited the ATP‐sensitive K+current in a dose‐dependent manner.
Voltage‐sensitive K+currents were unaffected by 20 μm but decreased slightly by 100 μm clonidine.
Calcium currents, measured by the whole cell or perforated patch technique, were unaffected by clonidine at concentrations up to 100 μm.
It is concluded that high concentrations of the α2‐adrenoceptor agonist clonidine, but not of adrenaline, can inhibit ATP‐sensitive K+channels in pancreatic β‐cells. Other ionic channels are only slightly affected or unaffected.
In vitro modulation of the eosinophil‐dependent enhancement of the permeability of the bronchial mucosa
Authors: Herbert Carolyn A. , Edwards David , Boot John R. , Robinson Clive 
Published: July 2012

Basolateral to apical albumin flux has been measured in sheets of bovine bronchial and tracheal mucosa mounted in vitro.
Addition of guinea‐pig peritoneal eosinophils or neutrophils to the basolateral side of such tissues had no significant influence on the transmucosal flux of albumin in either the bronchial or tracheal mucosa.
Stimulation of eosinophils or neutrophils by the calcium ionophore A23187, or by their presentation to an opsonized airways mucosa, resulted in a significant increase in the transbronchial flux of albumin. This effect was seen after only 60 min incubation of the leucocytes with the bronchial mucosa, and was no greater when the contact time was extended to 180 min. Incubation of bronchial mucosal tissues with 1 mg ml−1polyarginine for 3 h produced a significant increase in albumin flux, but was ineffective at 0.5 mg ml−1.
In contrast to the bronchial mucosa, the tracheal mucosa appeared resistant to the effects of stimulated eosinophils and neutrophils.
The lipoxygenase inhibitor AA‐861 failed to influence the ability of eosinophils to augment the transmembrane flux of albumin. However, insertion of a Millipore filter mask between the eosinophils and the bronchial mucosa significantly inhibited the eosinophil‐dependent enhancement of mucosal permeability.
The broad spectrum antiproteinase α2‐macroglobulin achieved almost total ablation of the action of stimulated eosinophils in the bronchial mucosa. These results suggest that proteinases may make a significant contribution to the genesis of epithelial injury, whereas leukotrienes do not.
The sources of calcium for carbachol‐induced contraction in the circular smooth muscle of guinea‐pig stomach
Authors: Parekh Anant B. , Brading Alison F. 
Published: July 2012

The action of carbachol on the mechanical activity of circular muscle from guinea‐pig upper stomach was studied. High concentrations of carbachol (e.g. 10−4m) produced a rapid phasic contraction followed by a smaller, sustained tonic contraction. Low concentrations (e.g. 10−7m) caused a contraction which did not generally show marked distinction between phasic and tonic components.
The response to 10−7m carbachol was very sensitive to 10−5m nifedipine as was the phasic response to 10−4m carbachol. The tonic contraction to the latter, however, was only slightly reduced by nifedipine.
The carbachol‐induced contractions remaining in the presence of nifedipine were dose‐related and very dependent on the presence of external calcium.
Carbachol, 10−7m, did not produce a contraction after 4 min exposure to calcium‐free solution whereas 10−4m carbachol did and this was phasic in nature but much reduced relative to the control in normal Ca.
A phasic followed by a small tonic contraction to 10−4m carbachol was seen superimposed on the K contracture in tissues depolarized with 100 mm K, whereas only a small tonic response occurred for 10−7m carbachol.
In the absence of a functional carbachol‐sensitive intracellular store, 10−4m carbachol was unable to trigger a contraction in calcium‐free solution. However, when calcium was simultaneously readmitted with carbachol after exposure to calcium‐free solution, a contraction occurred.
Carbachol, 10−7m, did not significantly increase inositol polyphosphate levels, whereas 10−4m carbachol did. The increase with 10−4m occurred rapidly peaking within 2 min and was undetectable after 5 min, in the absence of lithium.
It is concluded that low concentrations of muscarinic agonist trigger a contraction predominantly through a nifedipine‐sensitive route whereas higher concentrations further utilize intracellular calcium release and a receptor‐operated extracellular calcium‐dependent pathway. The former is probably associated with the phasic component and the latter with the tonic one.
Opioid activity of dermenkephalin analogues in the guinea‐pig myenteric plexus and the hamster vas deferens
Authors: Sagan Sandrine , Corbett A.D. , Amiche M. , Delfour A. , Nicolas P. , Kosterlitz H.W. 
Published: July 2012

To elucidate the structural features required for selective and potent action of dermenkephalin at the δ‐opioid receptor, a series of analogues of dermenkephalin and dermorphin were tested for their effectiveness in depressing electrically‐evoked contractions of the vas deferens of the hamster (δ‐opioid receptors) and the guinea‐pig myenteric plexus‐longitudinal muscle preparation (μ‐ and κ‐opioid receptors).
Dermenkephalin was more selective and more potent at δ‐receptors than the δ‐ligand [d‐Pen2, d‐Pen5]‐enkephalin. The responses to dermenkephalin in the hamster vas deferens were increased by addition of peptidase inhibitors; the maximum effect was obtained with 3 μm thiorphan.
[l‐Met2]‐dermenkephalin had 0.2% and [l‐Ala2]‐dermorphin 0.01% of the agonist activity of the corresponding endogenous peptides which have d‐amino acids in position 2. The pharmacological activity of these analogues was unaffected by inhibition of peptidases. This emphasizes the role that the d‐configuration plays in determining the bioactive folding of these highly active peptides.
Dermenkephalin‐(1–6)‐NH2 was more potent at δ‐receptors than at μ‐receptors whereas, dermenkephalin‐(1–4)‐NH2 is a selective μ‐agonist, having no activity at δ‐receptors.
Substitution of the C‐terminal tripeptide of dermorphin with the C‐terminal tripeptide of dermenkephalin abolished the μ‐receptor preference of dermorphin. The resulting hybrid peptide, Tyr‐d‐Ala‐Phe‐Gly‐Leu‐Met‐Asp‐NH2 was as potent as dermenkephalin at δ‐receptors. A shift towards a preference for δ‐receptors was obtained when the C‐terminal tetrapeptide of dermorphin was replaced by the C‐terminal tetrapeptide of dermenkephalin.
Substitution of Asp by Asn in position 7 of dermenkephalin caused an increase in μ‐receptor potency and a decrease in δ‐receptor potency, resulting in a 20 fold decrease in μ‐receptor selectivity. Dermenkephalin‐(1–6)‐NH2 and [Asn7]‐dermenkephalin have almost identical δ‐receptor agonist potencies and ratios of IC50 in the myenteric plexus to IC50 in the hamster vas deferens.
The results obtained emphasise the importance of a negative charge at the C‐terminus of dermenkephalin for selectivity at the δ‐opioid receptor. Furthermore, the hydrophobic residues Leu5and Met6may be critical in ensuring tight binding to the receptor which results in high agonist potency.
The long‐term effects of the rodenticide, brodifacoum, on blood coagulation and vitamin K metabolism in rats
Authors: Mosterd J.J. , Thijssen H.H.W. 
Published: July 2012

The long‐term (30 days) effects of a single dose of brodifacoum (0.2 mg kg−1, orally) on blood clotting activity and on liver parameters of the vitamin K cycle were investigated in rats. Maximal effect on blood clotting activity was seen on day one. On day seven blood clotting activity had returned to normal.
Liver microsomal vitamin KO reductase activity was maximally suppressed (10% of control activity) on day one, steadily recovered to about 40% on day 15 to remain at that level. The same time course was seen for the number of microsomal warfarin binding sites.
The persistent inhibition of the vitamin K cycle was also verified in vivo; following vitamin K administration (10 mg kg−1, i.v.) on day 30, the brodifacoum‐treated rats accumulated vitamin KO in the liver.
Although clotting factor synthesis was normal, brodifacoum‐treated rats were highly sensitive to warfarin.
Brodifacoum rapidly accumulated in the liver until the saturation of the microsomal binding site. Brodifacoum binding to the target prevented its elimination from the liver; liver content on day 30 was not different from day 7.
The results show (1) an over capacity for the hepatocellular vitamin K cycle, (2) a dissociation of the vitamin K epoxidation and the vitamin K‐dependent carboxylation, (3) the ‘superwarfarin’ rodenticides to be extremely persistent due to their binding to the target.
Effects of BRL 38227 on potassium currents in smooth muscle cells isolated from rabbit portal vein and human mesenteric artery
Authors: Russell Scott N. , Smirnov Sergey V. , Aaronson Philip I. 
Published: July 2012

Single smooth muscle cells were isolated from the rabbit portal vein and the human mesenteric artery and whole cell currents recorded at room temperature from either cell type by the whole cell voltage clamp technique.
In the rabbit portal vein cells addition of 10 μm BRL 38227 induced a quasi‐instantaneous, voltage‐insensitive and time‐independent current which had a reversal potential of −75 mV under experimental conditions where the calculated EK was −83 mV.
Cells were held at 0 mV and BRL 38227 was added cumulatively to construct a dose‐response relationship. BRL 38227 (0.03–10 μm) caused a dose‐dependent outward shift in the holding current with an EC50 of 1.3 μm.
BRL 38227 (10 μm) had no effect on the delayed rectifier K+ current measured in the presence of 5 mm tetraethylammonium and no effect on the Ca2+‐activated K+ current measured in the presence of 5 mm 4‐aminopyridine. Similarly BRL 38227 had no effect on the Ca2+ current.
The BRL 38227‐induced current was blocked by glibenclamide (10 μm) and phentolamine (100 μm), specific blockers of the ATP‐sensitive K+ current in single cells.
In human isolated mesenteric artery cells, BRL 38227 (10 μm) induced a glibenclamide‐sensitive current similar to, but smaller than, that observed in the rabbit portal vein.
We conclude that in these cells, BRL 38227 activates a potassium conductance which has the electrophysiological and pharmacological characteristics of ATP‐sensitive K+ channels.
Impaired endothelium‐dependent relaxation of dog coronary arteries after myocardial ischaemia and reperfusion: prevention by amlodipine, propranolol and allopurinol
Authors: Sobey Christopher G. , Dalipram Romina A. , Dusting Gregory J. , Woodman Owen L. 
Published: July 2012

Anaesthetized, open‐chest dogs were subjected to 60 min of left circumflex coronary artery occlusion followed by 90 min of reperfusion. Endothelium‐dependent and ‐independent relaxant responses of the isolated coronary arterial rings were then investigated.
The endothelium‐dependent, acetylcholine‐induced relaxation of ischaemic/reperfused arterial rings was significantly attenuated in comparison to control rings (1.9 fold rightward shift, ischaemic/reperfused maximum relaxation = 57 ± 13% of control maximum relaxation; P < 0.05). In contrast, glyceryl trinitrate produced similar relaxant responses in control and ischaemic rings.
Pretreatment of dogs with either amlodipine (3 μg kg−1 min−1, i.v.) or propranolol (1 mg kg−1, i.v.) completely prevented the postischaemic impairment of endothelium‐dependent relaxant responses (100 ± 3% and 90 ± 5% of control maximum relaxation, respectively).
Allopurinol pretreatment (25 mg kg−1, p.o. 24 h previously, plus 50 mg kg−1 i.v. 5 min before arterial occlusion) partially protected against endothelial dysfunction by preventing the ischaemia‐induced rightward shift of the acetylcholine relaxation curve and increasing the maximum relaxation response (83 ± 7% of control rings).
These results confirm that endothelium‐dependent coronary vascular relaxation is impaired by ischaemia and reperfusion, and that the ischaemia‐induced impairment is reduced by pretreatment with amlodipine, propranolol or allopurinol.
Effect of sulphur containing amino acids on [3H]‐acetylcholine release from amacrine cells of the rabbit retina
Authors: Neal Michael J. , Cunningham Jo R. 
Published: July 2012

The effects of the sulphur containing amino acids, homocysteic acid, homocysteine sulphinic acid, cysteic acid and cysteine sulphinic acid on the release of [3H]‐acetylcholine ([3H]‐ACh) from the cholinergic amacrine cells of the rabbit retina were examined.
All the compounds stimulated the spontaneous resting release and abolished the light‐evoked release of [3H]‐ACh. Except for homocysteine sulphinic acid these actions occurred at concentrations that did not affect the erg b‐wave amplitude, indicating a site of action at the inner retina.
N‐methyl‐d‐aspartate (in Mg2+‐containing medium) clearly blocked the effects of homocysteic acid and homocysteine sulphinic acid on the resting release of [3H]‐ACh but had no effect on the actions of cysteic acid and cysteine sulphinic acid.
Since N‐methyl‐d‐aspartate is an antagonist of the light‐evoked endogenous bipolar cell transmitter released onto cholinergic cells, these results are consistent with the suggestion that homocysteic acid or homocysteine sulphinic acid may be a transmitter released from this subpopulation of bipolar cells.
The present experiments indicate the existence of excitatory amino acids that have closer pharmacological properties to a bipolar cell transmitter than glutamate but it remains to be seen whether homocysteic acid or homocysteine sulphinic acid occur in these particular bipolar cells.
Studies on the mechanism of 5‐HT1 receptor‐induced smooth muscle contraction in dog saphenous vein
Authors: Sumner Michael J. , Feniuk Wasyl , McCormick Julie D. , Humphrey Patrick P. A. 
Published: July 2012

We have investigated the mechanism of smooth muscle contraction evoked by activation of 5‐HT1‐like receptors in dog isolated saphenous vein.
In the presence of the 5‐HT2 receptor antagonist, ritanserin (0.1 μm), concentration‐effect curves (10 nm‐300 μm) for 5‐hydroxytryptamine (5‐HT)‐induced smooth muscle contraction were biphasic. This could be attributed to a direct action on 5‐HT1‐like receptors at low concentrations of 5‐HT (10 nm‐10 μm) and an indirect (through the release of noradrenaline from sympathetic neurones) activation of postjunctional α‐adrenoceptors at higher 5‐HT concentrations. In contrast, concentration‐effect curves (100 nm–100 μm) for sumatriptan‐induced contractions were not biphasic, and were due solely to activation of 5‐HT1‐like receptors.
Smooth muscle contractions evoked either by low concentrations of 5‐HT or by sumatriptan were abolished by removal of extracellular calcium and were markedly inhibited, but not abolished, by the calcium channel blocker, verapamil (1–30 μm). In contrast, contractions evoked by high concentrations of 5‐HT were markedly less sensitive to removal of extracellular calcium or to verapamil.
5‐HT and sumatriptan also inhibited (to a maximum of about 50%) prostaglandin E2 (PGE2,5 μm)‐stimulated adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) formation. This effect was mimicked by the α2‐adrenoceptor agonist, azepexole (B‐HT933) but not by the α1‐adrenoceptor agonist, methoxamine.
In contrast to mediation of smooth muscle contraction, the 5‐HT1‐like receptor‐mediated inhibition of PGE2‐stimulated cyclic AMP formation evoked by 5‐HT or sumatriptan was not attenuated by removal of extracellular calcium or by verapamil (1 μm).
A directly‐acting inhibitor of adenylyl cyclase, 2′,3′‐dideoxyadenosine (1 mm) inhibited PGE2‐stimulated cyclic AMP formation but did not produce smooth muscle contraction.
These results suggest that contractile responses of dog isolated saphenous vein arising through activation of 5‐HT1‐like receptors are associated with both an influx of extracellular calcium ions (to a large extent via voltage‐dependent channels) and an inhibition of adenylyl cyclase. However, although these two responses are coupled to the same receptor, they appear to be independent.
The effect of lipopolysaccharide, interleukin‐1 and tumour necrosis factor on the hepatic accumulation of 5‐hydroxytryptamine and platelets in the mouse
Authors: Endo Yasuo , Nakamura Masanori 
Published: July 2012

Injection of lipopolysaccharide (LPS; 0.5–500 μg kg−1) into mice induced a dose‐dependent, slowly developing increase in hepatic content of 5‐hydroxytryptamine (5‐HT). This sustained increase could not be attributed to an LPS‐induced alteration of the pharmacokinetic handling of 5‐HT by stimulation of its uptake or inhibition of its degradation.
Regional differences were apparent in the tissue content of histamine and 5‐HT between mast cell‐deficient (W/Wv) and normal (+/ +) mice. LPS administration (0.5 mg kg−1) gave comparable increases in the hepatic level of 5‐HT in mast cell‐deficient and normal mice.
Reserpine pretreatment (1 mg kg−1) selectively reduced 5‐HT levels in the blood, spleen, liver, brain and lung of normal mice. Prior treatment with this agent also abolished the LPS (0.5 mg kg−1)‐induced hepatic accumulation of 5‐HT.
Accumulation of 5‐HT in the liver by LPS (0.1 mg kg−1) was temporally associated with both a fall in the levels of circulating platelets, and a reduction in the concentration of 5‐HT in the blood. The LPS dose‐dependent (0.5–500 μg kg−1) increase in hepatic 5‐HT content was associated with a similar dose‐dependent reduction in the circulating levels of 5‐HT.
Interleukin‐1, α and β (10 μg kg−1) and tumour necrosis factor α (TNFα) (1 mg kg−1) significantly enhanced the accumulation of 5‐HT within the liver. Administration of TNFα (10 μg kg−1) potentiated the increase in hepatic 5‐HT content seen with IL‐1β (10 μg kg−1).
Electron microscopy revealed numerous platelets in the sinusoidal and perisinusoidal Disse spaces within the liver, in animals pretreated with LPS (0.1 mg kg−1). The platelets retained their intact structure and showed no evidence of degranulation.
These data suggest that the LPS and cytokine‐induced mobilization of 5‐HT in the liver is associated with the hepatic translocation of platelets. This migration appears to be independent of platelet aggregation.