bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of E. coli STa enterotoxin on the absorption of weakly dissociable drugs from rat proximal jejunum in vivo
Authors: McEwan G.T.A. , Lucas M.L. 
Published: July 2012

The effect of E. coli heat stable (STa) enterotoxin on the absorption of radio‐labelled weak electrolytes and their appearance in peripheral blood was assessed in vivo by use of an intestinal recirculation procedure.
STa reduced the luminal disappearance (P > 0.02) and peripheral blood appearance (P > 0.02) of label from salicylic acid as well as the luminal disappearance (P > 0.02) of diphenylhydantoin.
In contrast, STa increased the appearance in peripheral blood and disappearance from the lumen of label from morphine (P > 0.05), amphetamine (P > 0.01) and lignocaine (P > 0.01).
Increased weak base (lignocaine) absorption can also be achieved by a combination of forskolin and theophylline which resembles STa in its ability to neutralise the usually acid surface pH of the proximal jejunum.
Increased weak base absorption and hindered weak acid absorption occurs despite a uniform reduction in net fluid absorption after STa exposure, making it unlikely that variations in fluid absorption account for the variations in drug absorption.
The ability of STa to elevate the mucosal surface pH (or acid microclimate) to neutral values, thereby altering the proportion of uncharged weak‐electrolyte, may explain its different effects on weak acids and bases; neutralisation of the acid microclimate would increase the amount of undissociated weak base available for uptake.
Actions of acetylcholine and GABA on spontaneous contractions of the filariid, Dipetalonema viteae
Authors: Christ Daryl , Goebel Michael , Saz Howard J. 
Published: July 2012

Isotonic contractions were recorded from the filarial nematode, Dipetalonema viteae (Acanthocheilonema viteae), in an isolated tissue chamber.
Nicotine (10−6 m) and pilocarpine (10−5 m) increased the spontaneous contractions in the intact filariid, but acetylcholine (ACh, 10−4 m) and muscarine (10−5 m) were inactive.
When ACh was applied to an opened D. viteae, it was 10,000 times more potent. This indicates that the cuticle is an effective barrier to the penetration of ACh to the muscle cells.
The effects of ACh on the opened D. viteae were not affected by hexamethonium (10−3 m) or atropine (10−5 m) and were only partially reduced by (+)‐tubocurarine (10−4 m).
γ‐Aminobutyric acid (GABA, 10−3 m) reduced the spontaneous activity of the intact D. viteae; however, the effect of GABA had a slow onset and recovery. Muscimol (10−5 m) was more potent than GABA and had a more rapid onset and recovery.
GABA was 1,000 times more potent on the opened D. viteae than on the intact D. viteae. Baclofen (10−3 m) was inactive on both preparations.
The effect of GABA was not antagonized by bicuculline (10−4 m), picrotoxin (10−5 m) or penicillin G (10−3 m).
It is concluded that the filariid cuticle acts like a lipid structure and blocks the penetration of polar substances, such as ACh and GABA. Also, due to the lack of efficacy of the ACh and GABA antagonists, it was concluded that the nematode receptors are somewhat different from the mammalian ACh and GABA receptors.
Differences in control of descending inhibition in the proximal and distal regions of rat colon
Authors: Hata Fumiaki , Kataoka Toshiya , Takeuchi Tadayoshi , Yagasaki Osamu , Yamano Naoyuki 
Published: July 2012

Descending inhibition in the proximal and distal portions of rat colon was studied separately, in vitro.
In the proximal colon, localized distension with a small balloon caused three types of response (contraction; relaxation; relaxation, then contraction) of the circular muscle on the anal side of the distended region.
Distension caused descending relaxation of circular muscle in all segments of the proximal colon, although for this prostaglandin F2α (PGF2α) was necessary in some segments to increase muscle tone.
Atropine and guanethidine did not inhibit this descending relaxation, but tetrodotoxin did.
Hexamethonium inhibited the descending relaxation in 14 of 17 preparations of proximal colon tested, but not in the others.
In the distal colon, distension consistently caused an increase in the tone of the circular muscles. Descending relaxation was observed only after development of higher tone. Atropine and guanethidine did not inhibit the relaxation, but tetrodotoxin did.
Hexamethonium did not inhibit the descending relaxation in most of the preparations of distal colon examined.
AF64A, an inhibitor of choline uptake, inhibited the response mediated by cholinergic neurones in vitro to electrical transmural stimulation of the longitudinal muscle of proximal colon.
Treatment of colonic preparations with AF64A in vitro resulted in inhibition of descending relaxation in those of proximal, but not those of distal, colon.
The participation of intrinsic cholinergic neurones in the descending neuronal pathway is strongly suggested by the results in the proximal colon, but less so in the distal colon.
The tone and spontaneous contractile activity of colonic circular muscles are discussed in relation to their neuronal control.
No evidence for differences between pre‐ and postjunctional α2‐adrenoceptors in the periphery
Authors: Connaughton Sonia , Docherty J.R. 
Published: July 2012

We have compared prejunctional α2‐adrenoceptors in rat and guinea‐pig vas deferens and rat and guinea‐pig atria with postjunctional α2‐adrenoceptors in human saphenous vein and human platelets employing the antagonists yohimbine and SK&F 104078 and other α2‐adrenoceptor antagonists.
Yohimbine was approximately 10 times more potent prejuunctionally than SK&F 104078 at antagonizing the inhibition by the α2‐adrenoceptor agonist xylazine of stimulation‐evoked contractions in rat and guinea‐pig vas deferens, and at increasing stimulation‐evoked release of tritium in rat and guinea‐pig atria pre‐incubated with [3H]‐noradrenaline.
Yohimbine was approximately 10 times more potent postjunctionally than SK&F 104078 at antagonizing contractions to noradrenaline in human saphenous vein and at displacing [3H]‐yohimbine binding in human platelet membranes.
For the antagonists yohimbine, SK&F 104078, prazosin, phentolamine, CH 38083 and urapidil, there was a significant correlation between prejunctional potency in rat vas deferens atrium and postjunctional potency in human platelet, although the correlation was improved by the omission of prazosin.
We have no evidence for differences between functional pre‐ and postjunctional α2‐adrenoceptors in the periphery, although these functional receptors may differ from the ligand binding site in the human platelet.
Chronic exposure of cultured endothelial cells to eicosapentaenoic acid potentiates the release of endothelium‐derived relaxing factor(s)
Authors: Boulanger Chantal , Schini Valérie B. , Hendrickson Helen , Vanhoutte Paul M. 
Published: July 2012

The effect of chronic exposure of cultured porcine aortic endothelial cells to eicosapentaenoic acid on the release of indomethacin‐insensitive relaxing factor(s) was investigated (a) under bioassay conditions using preconstricted canine coronary artery rings without endothelium and (b) by the measurement of guanosine 3′:5′‐cyclic monophospate (cyclic GMP) content of endothelial cells.
Exposure of endothelial cells for 8–10 days to eicosapentaenoic acid (2.5 × 10−5 m) did not affect the relaxing activity of the perfusate from unstimulated endothelial cells.
The treatment with eicosapentaenoic acid significantly increased the relaxation of the bioassay ring observed upon stimulation of the endothelial cells with adenosine diphosphate (3 × 10−8 m to 3 × 10−4 m) and, to a lesser extent with bradykinin (10−8 to 3 × 10−8 m), while the relaxing activity evoked by the calcium ionophore A23187 (3 × 10−7 m) was not affected. Neither acetylcholine (10−6 m) nor 5‐hydroxytryptamine (10−6 m) stimulated the release of relaxing factor(s) from control or eicosapentaenoic acid‐treated endothelial cells.
Bradykinin (10−7 m), adenosine diphosphate (3 × 10−5 m), the calcium ionophore A23187 (10−6 m) and nitric oxide (2 × 10−6 m) stimulated haemoglobin‐sensitive increases in cyclic GMP content of porcine endothelial cells which were unaffected by prior chronic exposure to eicosapentaenoic acid.
These results suggest that chronic exposure of porcine aortic endothelial cells to eicosapentaenoic acid increases the release of relaxing factor(s) in response to activation of membrane‐associated receptors for purines and kinins. The lack of effect of eicosapentaenoic acid treatment on agonist‐stimulated production of cyclic GMP suggests that the enhanced relaxation observed under bioassay conditions is not due to an increased production of nitric oxide.
Effect of 5‐HT3 receptor antagonists on responses to selective activation of mesolimbic dopaminergic pathways in the rat
Authors: Hagan R.M. , Jones B.J. , Jordan C.C. , Tyers M.B. 
Published: July 2012

The effects of 5‐hydroxytryptamine3 (5‐HT3) receptor antagonists on the behavioural hyperactivity response which results from injection of the neurokinin receptor agonist [pGlu5, MePhe8, Sar9]‐substance P (5–11) (DiMe‐C7) into the ventral tegmental area (VTA) of the rat midbrain have been determined.
Subcutaneous administration of ondansetron (GR38032) (0.001–0.3 mg kg−1), GR65630 (0.01 mg kg−1), ICS 205–930 (0.1 mg kg−1) and MDL 72222 (0.1 mg kg−1), inhibited the DiMe‐C7‐induced hyperactivity response.
The effects of ondansetron on DiMe‐C7‐induced changes in dopamine and 5‐HT metabolism in discrete areas of rat forebrain were studied in order to investigate further the possible mechanism of action of 5‐HT3 antagonists in modifying mesolimbic dopaminergic systems.
Intra‐VTA administration of DiMe‐C7 increased levels of dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens, olfactory tubercules and right amygdala, indicating increased mesolimbic dopamine metabolism. DOPAC levels were not significantly increased in the frontal cortex, left amygdala or striatum. Dopamine levels were not altered in any of these brain areas. DiMe‐C7 also increased 5‐hydroxyindoleacetic acid (5‐HIAA) levels in the amygdala but this was only statistically significant in the right amygdala. 5‐HT levels were not changed significantly by DiMe‐C7 treatment.
In control rats, pretreatment with ondansetron (0.1 mg kg−1) had no effect on the levels of dopamine, 5‐HT or their metabolites, but in rats given DiMe‐C7, ondansetron significantly inhibited the increase in DOPAC levels in the nucleus accumbens.
These results are in agreement with the proposed facilitatory role of 5‐HT3 receptor activation on mesolimbic dopaminergic transmission, and suggest that 5‐HT3 antagonists may have important therapeutic indications for the treatment of CNS disorders in which mesolimbic dopamine systems are perturbed.
An examination of the sources of calcium for contractions mediated by postjunctional α1‐ and α2‐adrenoceptors in several blood vessels isolated from the rabbit
Authors: Daly C.J. , Dunn W.R. , McGrath J.C. , Miller D.J. , Wilson V.G. 
Published: July 2012

The roles of intracellular and extracellular‐derived Ca2+ in α‐adrenoceptor‐mediated contractions to noradrenaline (NA) have been investigated in several isolated blood vessels from the rabbit by examining responses in the presence of a modified Krebs‐Henseleit saline with 2.5 mm Ca2+ and a Ca2+‐buffered saline with 0.1 μm free Ca2+.
NA was tested in preparations of the abdominal aorta, distal saphenous artery, renal vein, lateral saphenous vein, plantaris vein and ear vein exposed to a Ca2+‐buffered saline with 0.1 μm [Ca2+]. A concentration of NA which was maximally effective in modified Krebs‐Henseleit saline, produced an initial transient contraction (ITC) followed by a relaxation towards baseline. This is evidence that α‐adrenoceptor‐mediated responses in all these blood vessels depend upon calcium from both sources.
The ITC was particularly pronounced in the arteries and was associated more closely with the α1‐receptor subtype. In the abdominal aorta, distal saphenous artery and renal vein the ITC can almost exclusively be attributed to an α1‐adrenoceptor (prazosin‐sensitive, rauwolscine‐resistant). In the ear vein, and to a lesser extent the plantaris vein, the ITC was mediated in part by an α2‐adrenoceptor (prazosin‐resistant, rauwolscine‐sensitive).
α2‐Adrenoceptors in the lateral saphenous vein largely account for the response to NA in modified Krebs‐Henseleit saline, but α1‐adrenoceptors mediate the ITC in Ca2+‐buffered saline. After selective inactivation of α1‐adrenoceptors with a combination of phenoxybenzamine and rauwolscine, responses to NA in modified Krebs‐Henseleit saline are slow in onset and there is no ITC in Ca2+‐buffered saline.
The possible significance of the coupling of postjunctional α2‐adrenoceptors to dual sources of Ca2+ is discussed in relation to the interaction between α‐adrenoceptor subtypes and the ease of demonstrating functional α2‐adrenoceptors in isolated blood vessels.
Resiniferatoxin, a potent capsaicin‐like stimulator of peripheral nociceptors in the neonatal rat tail in vitro
Authors: Dray A. , Bettaney J. , Forster P. 
Published: July 2012

A spinal ventral root response was measured following the activation of peripheral fibres by noxious (heat at 48°C, capsaicin, bradykinin) and innocuous (brush) stimuli in a preparation of the neonatal rat spinal cord‐tail maintained in vitro.
Following superfusion of the tail with 0.1–1.0 nm of the potent irritant, resiniferatoxin (RTX), brief, irregular depolarization and a selective loss of capsaicin sensitivity was produced. RTX 10–100 nm evoked a tonic response, initiated transient irregular depolarizations and densitization to further applications of RTX and capsaicin but not to other stimuli. Following RTX 1 μm a prolonged loss of sensitivity to all noxious stimuli was produced.
When a selective densitization to capsaicin was produced by a long application of capsaicin, RTX was also ineffective.
Superfusion of the tail with 4β‐phorbol, 12, 13‐dibutyrate (PDBu), a protein kinase C activator, stimulated capsaicin‐sensitive peripheral fibres. Prolonged administration of PDBu attenuated or abolished further responses to PDBu and bradykinin but responses to RTX and capsaicin were unchanged. The protein kinase C inhibitor staurosporine (50–200 nm), attenuated the effects of PDBu and bradykinin but not those of RTX or capsaicin.
The present data suggest that neither RTX nor capsaicin act on peripheral nociceptors via a phorbol ester‐like stimulation of protein kinase C. Rather, RTX acts on nociceptors by a similar mechanism to capsaicin. These effects may be the basis for the irritant properties of RTX and may further relate to the antinociceptive actions observed in vivo. RTX is therefore a potent new tool with which to investigate the properties of nociceptive neurones and provides a prototype for further development of antinociceptive agents.
Effect of neuropeptide Y on cardiac output, its distribution, regional blood flow and organ vascular resistances in the pithed rat
Authors: MacLean Margaret R. , Hiley C. Robin 
Published: July 2012

The effects of neuropeptide Y on cardiac output, its distribution and organ vascular resistances were determined with tracer microspheres in pithed rats.
Neuropeptide Y increased blood pressure by increasing both cardiac output and total peripheral resistance. The increase in cardiac output was due to an increase in stroke volume as heart rate was not changed. Increased vascular resistance in the splenic, renal, testicular, epididimidal, skeletal muscle, large intestinal and mesenteric vascular beds contributed to the increase in total peripheral resistance. Vasoconstriction was most pronounced in the mesenteric bed.
This study indicates that neuropeptide Y increases blood pressure by increasing cardiac output and total peripheral resistance. The increased cardiac output is possibly due to an increase in venous return, whilst the increased total peripheral resistance was due to regional vasoconstriction, particularly in the mesenteric bed.
Effects of pinaverium on voltage‐activated calcium channel currents of single smooth muscle cells isolated from the longitudinal muscle of the rabbit jejunum
Authors: Beech D.J. , MacKenzie I. , Bolton T.B. , Christen M.O. 
Published: July 2012

Smooth muscle cells of the longitudinal muscle of the rabbit jejunum were dispersed by enzyme treatment and recordings of membrane current were made in the whole‐cell mode by patch clamp technique. The action of pinaverium bromide on the voltage‐dependent inward current of single isolated smooth muscle cells was studied in solutions containing normal concentrations of calcium or high concentrations of barium at room temperature.
Pinaverium reduced the voltage‐dependent inward current with an IC50 of 1.5 μm. This IC50 is similar to those of verapamil, diltiazem and flunarizine on these cells as described by others. Occasionally evidence of a potentiating action of pinaverium on the inward current was seen.
Repetitive stimulation of the cells did not increase blockade of inward current by pinaverium unlike the use‐dependent blockade seen with verapamil, methoxyverapamil, and diltiazem in these and in other smooth muscle cells.
The inactivation of inward current was studied by holding at various potentials for 2 or 10 s before evoking inward current. The voltage at which current was 50% available was changed very little by pinaverium although other calcium entry blockers, for example the dihydropyridines, have been reported to produce appreciable negative shifts which indicate considerable voltage‐dependence of their blockade. This may indicate that pinaverium has similar affinities for the closed available and inactivated calcium channel states so that blockade is not appreciably voltage‐dependent.
Atropine‐resistant relaxation induced by high K+ in iris dilator muscle of the rat and pig
Authors: Ryang S. , Takei S. , Kawai T. , Imaizumi Y. , Watanabe M. 
Published: July 2012

The effects of high K+ ion concentration on the isometric tension in dilator muscle strips of the rat and porcine iris were examined. A high K+ solution, prepared by the replacement of Na+ in the medium with equimolar K+, was applied in the presence of 1 μm phentolamine, 1 μm propranolol and 1 or 10 μm atropine. High K+ (> 20 mm) induced a biphasic response; an initial phasic contraction followed by relaxation rather than tonic contraction.
An additional application of a Ca2+ antagonist, 1 μm nifedipine or nicardipine, almost completely blocked the K+‐induced initial contraction and enhanced the following relaxation. The effect of K+ under these conditions was concentration‐dependent in the range 20 to 80 mm. The maximum amplitude of the atropine‐resistant relaxation induced by high K+ corresponds to 50–75% of that produced by acetylcholine in the absence of atropine. A similar K+‐induced relaxation was observed in the porcine iris dilator.
The atropine‐resistant relaxation in the rat iris dilator was not affected by pretreatment with 10 μm ouabain. The relaxation induced by 40 or 80 mm K+ in the porcine dilator was slightly enhanced or not affected, respectively, in the presence of 1 μm ouabain. Application of 10 μm ouabain per se induced relaxation in the porcine iris dilator.
The low Na+ ion concentration present in high K+ solutions was not responsible for the K+‐induced relaxation since the complete replacement of Na in the medium with Tris did not affect significantly the relaxation produced by high K+‐containing solutions.
Neither 1 μm tetrodotoxin, 10 μm indomethacin, 10 μm nordihydroguaiaretic acid nor hypoxic conditions affected the high K+‐induced relaxation.
The inherent tone of the rat iris dilator was not affected by either 8‐bromo cyclic GMP, dibutyryl cyclic GMP (0.1‐0.3 mm) or nitroprusside (1–100 μm).
These results may suggest that the atropine‐resistant relaxation induced by high K+ is not due to either activation of the Na‐K pump or release of a relaxing factor produced by oxidative metabolism. Although the relaxation mechanism has not been elucidated, it is probably not mediated by an increase in cellular cyclic GMP levels.
Tetrahydroaminoacridine (tacrine) stimulates neurosecretion at mammalian motor endplates
Authors: Thesleff S. , Sellin L.C. , Tågerud S. 
Published: July 2012

Tacrine (20 μm) induced, like 4‐aminoquinoline (4‐AQ, 200 μm), the appearance of a population of miniature endplate potentials (m.e.p.ps) with more than twice the normal amplitude or time‐to‐peak. The times‐to‐peak of nerve impulse‐evoked endplate potentials were not similarly affected.
Cholinesterase inhibition by edrophonium (25 μm) did not prevent tacrine or 4‐AQ from inducing this population of m.e.p.ps.
Nerve‐muscle preparations in which the normal calcium‐sensitive quantal release of acetylcholine had been blocked by botulinum neurotoxin type A also responded to tacrine by an increase in the frequency of giant or slow m.e.p.ps.
Reduction of the temperature from 30° to 14°C reduced the frequency of giant or slow m.e.p.ps induced either by tacrine or by 4‐AQ. A similar effect was obtained by colchicine (5 mm). This supports the idea that proximo‐distal axonal transport is required for the secretory activity.
The neurosecretion evoked by tacrine could explain the therapeutic effects of the drug claimed in the treatment of Alzheimer's type of dementia.
Cigarette smoke, nicotine and capsaicin aerosol‐induced vasodilatation in pig respiratory mucosa
Authors: Matran Régis , Alving Kjell , Lundberg Jan M. 
Published: July 2012

Anaesthetized pigs were used to study vascular responses in the sphenopalatine artery (SPA), superior laryngeal artery (SLA) and bronchial artery (BA) upon exposure to cigarette smoke or aerosol of nicotine and capsaicin. Direct blood flow recordings were made with ultrasonic probes around the vessels.
Smoke from one cigarette was administered as inhalation for 2 min with or without a Cambridge filter which removes the particulate matter including nicotine from the smoke. Aerosols of nicotine (2.5 mg) or capsaicin (10 mg) were administered to the nose or the lower airways for 3 min.
Cigarette smoke exposure caused a reproducible reduction of the vascular resistance (VR) suggesting vasodilatation in the SPA, SLA, and especially the BA. The vasodilatation was not modified by the Cambridge filter, suggesting that it was caused by vapour phase components rather than nicotine.
The smoke effect was not changed after pretreatment with the cyclo‐oxygenase inhibitor, diclofenac, or with atropine, guanethidine, H1 or H2‐histamine receptor antagonists, nedocromil, or by vagotomy. The smoke‐evoked decrease in VR was not modified by the nicotinic receptor antagonist chlorisondamine in the SLA or BA.
In pigs pretreated with increasing doses of capsaicin two days earlier, the decrease in VR upon smoke exposure in both the BA and SLA was unaffected while the change in VR was attenuated in the SPA.
Nicotine aerosol had no effect on VR in the peripheral airways supplied by the BA while a decrease in VR was observed in the SLA and SPA. The nicotine response was reduced after capsaicin pretreatment in the nasal and upper tracheal circulation.
Capsaicin aerosol reduced VR in the vascular beds supplied by the SPA, SLA and BA and this response was markedly reduced after capsaicin pretreatment.
The mechanisms underlying vasodilatation upon cigarette smoke exposure in the bronchial mucosa are at the moment unclear while both non‐cholinergic parasympathetic and sensory components may be involved in the nose. Capsaicin induced a vasodilatation at all levels via sensory mechanisms, whereas nicotine‐evoked vasodilatation is restricted to the upper airway mucosa and is at least partly dependent on parasympathetic reflexes involving capsaicin‐sensitive sensory nerves.