bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropeptide Y, peptide YY and C‐terminal fragments release histamine from rat peritoneal mast cells
Authors: Grundemar Lars , Håkanson Rolf 
Published: July 2012

Neuropeptide Y (NPY) and peptide YY (PYY) seem to act on at least two receptor sybtypes, Y1 and Y2. The Y1‐receptor requires the whole C‐terminally amidated NPY/PYY molecule whereas the Y2‐receptor in addition recognizes C‐terminal fragments of the two peptides. The present study was designed to elucidate whether NPY and related peptides were able to release histamine from isolated peritoneal mast cells of the rat.
NPY, NPY 15–36, NPY 22–36, NPY 26–36 and desamido‐NPY evoked a concentration‐dependent release of mast‐cell histamine. The pEC15 values for NPY 15–36 and NPY 22–36 were higher, while the pEC15 value for NPY 26–36 was lower than that for NPY. At the highest concentration tested (0.1 mm), NPY and its C‐terminal fragments released between 30 and 40% of the total histamine content. At the same concentration desamido‐NPY released about 20%.
PYY and PYY 15–36 also evoked a concentration‐dependent release of mast‐cell histamine. PYY was more effective than PYY 15–36 since, at 0.1 mm, PYY released about 33%, while PYY 15–36 released about 15% of the total histamine content. Pancreatic polypeptide (PP) and the Y1‐receptor‐selective agonist [Pro34]NPY were virtually inactive.
The effect profile of the NPY/PYY‐related peptides suggests that they act on the mast cells by a mechanism that does not involve either of the receptor subtypes hitherto described. The kinetics of the NPY‐evoked histamine release may suggest that positively charged amino acid residues of NPY/PYY release mast‐cell histamine by a non‐receptor mechanism, as has been suggested for substance P and other basic peptides.
Variations in potassium concentration modify the inhibitory effect of lorcainide on myocardial Na+‐K+‐ATPase activity
Authors: Almotrefi Abdulrahman A. , Dzimiri Nduna 
Published: July 2012

The inhibitory action of lorcainide on the myocardial Na+‐K+‐ATPase (EC 3.6.1.3) activity was studied in guinea‐pig heart preparations at medium K+ concentrations of 2.5, 5.0 and 10 mm.
Lorcainide exhibited characteristically similar concentration‐dependent inhibitory effects at all three K+ concentrations tested. However, the inhibitory potencies were significantly increased at decreased K+ concentrations.
The IC50 values were 10.4 ± 3.2 μm at 2.5 mm, 28.3 ± 7.9 μm at 5.0 mm and 40.7 ± 9.2 μm at 10.0 mm K+ respectively. Thus, reduction in the K+ concentration from the ‘standard’ 5.0 to 2.5 mm enhanced the inhibitory potency of lorcainide, the effective concentrations being shifted towards much lower ranges, while increasing it to 10 mm on the other hand produced opposite but less marked effects.
These results show that the inhibition of myocardial Na+‐K+‐ATPase activity by lorcainide depends on the K+ concentration of the incubation medium. These effects are probably related to the mechanism by which lorcainide interferes with the electrogenic Na+/K+ pump activity of the enzyme, and hence may contribute to some of its cardiac actions.
Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor
Authors: Filep János G. , Sirois Martin G. , Rousseau Anne , Fournier Alain , Sirois Pierre 
Published: July 2012

The objectives of the present experiments were to assess the effects of endothelin‐1 on the macrovascular permeability in selected vascular beds, to study the involvement of platelet‐activating factor (PAF) in vascular responses to endothelin‐1 and to examine the vascular effects of combined administration of endothelin‐1 and PAF in conscious rats.
Intravenous bolus injection of endothelin‐1 (0.1–2 nmol kg−1) resulted in a dose‐dependent biphasic change in mean arterial blood pressure (MABP) with initial transient hypotension followed by a prolonged pressor action. These changes were accompanied by a dose‐dependent increase in haematocrit values.
Endothelin‐1 (0.1 and 1 nmol kg−1) increased dose‐dependently the vascular permeability of the trachea, upper and lower bronchi, stomach, duodenum, spleen and kidney (up to 240%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, liver and pancreas was not affected significantly by endothelin‐1 treatment.
Pretreatment of animals with the specific PAF receptor antagonist, WEB 2086 (1 mg kg−1, i.v.) or BN 52021 (10 mg kg−1, i.v.) reduced the endothelin‐1 (1 nmol kg−1)‐induced rise in haematocrit by about 50 and 30%, respectively. Both antagonists were highly effective at inhibiting protein extravasation in the stomach, duodenum and kidney. On the other hand, BN 52021, but not WEB 2086, significantly attenuated the effect of endothelin‐1 on permeability in the lower bronchi and spleen. Neither WEB 2086 nor BN 52021 modified the changes in MABP evoked by endothelin‐1.
When low doses of endothelin‐1 (0.1 nmol kg−1) and PAF (0.19 nmol kg−1) were administered simultaneously, enhanced protein extravasation was detected in the upper and lower bronchi, whereas neither endothelin‐1 nor PAF by themselves affected vascular permeability in these tissues. These changes occurred in the absence of significant changes in MABP.
Combined administration of higher doses of endothelin‐1 (1 nmol kg−1) and PAF (1.9 nmol kg−1) resulted in marked increases (up to 530%) in protein extravasation in the airways, pancreas, stomach and duodenum. The effect of endothelin‐1 on permeability was not affected by PAF in the spleen, whereas it was completely inhibited by PAF in the kidney. Combined injection of endothelin‐1 and PAF resulted in a slight, but significant increase in MABP.
The present findings show that endothelin‐1 is capable of increasing vascular permeability in selected vascular beds including the airways, gastrointestinal tract and kidney, and suggest that PAF may mediate, in part, its action on permeability, but not its hypotensive action. The present data also suggest that endothelin‐1 and PAF can act in concert to increase vascular permeability in rat airways and gastrointestinal tract.
Selective inhibition of K+ ‐stimulation of Na,K‐ATPase by bretylium
Authors: Tiku Patience E. , Nowell Peter T. 
Published: July 2012

The effects of bretylium were investigated on purified Na,K‐ATPase from guinea‐pig heart and on the Na/K pump in trout erythrocytes, with a view to further identifying the mechanism(s) associated with its antiarrhythmic effects.
Na,K‐ATPase activity of the thiocyanate‐dispersed enzyme was determined by the measurement of inorganic phosphate produced by ATP hydrolysis.
When the concentrations of each of the Na,K‐ATPase activating components were varied in turn, bretylium (1–5 mmol l−1) exhibited competitive‐type effects against K+ with a Ki of 1.4 mmol l−1 and noncompetitive‐type effects against Na+, Mg2+ and ATP.
In K+ influx studies in trout erythrocytes with 86Rb+ used as the marker, the inhibition of total influx observed with bretylium (5 and 10 mmol l−1) was attributable to the bretylium cation selectively inhibiting the Na/K pump‐mediated influx with the associated tosylate anion inhibiting Na/K cotransport.
The observed inhibition kinetics indicated that the bretylium cation (2–15 mmol l−1) competitively inhibited K+ stimulation of the Na/K pump at 6 and 1.25 mmol l−1 external K+ with a mean K1 of 2.3 mmol l−1.
The effects demonstrated on the functioning Na/K pump in erythrocytes confirmed the Na,K‐ATPase findings, with bretylium selectively inhibiting K+ stimulation of the pump mechanism in both cases.
It is suggested that Na,K‐ATPase inhibition may contribute to the antiarrhythmic and positive inotropic effects of bretylium with the cardiac accumulation of bretylium also possibly being a further important factor.
Inositol 1,4,5‐trisphosphate‐ and guanosine 5′‐O‐(3‐thio triphosphate)‐induced Ca2+ release in cultured airway smooth muscle
Authors: Chopra Lorna C. , Twort Charles H.C. , Cameron Ian R. , Ward Jeremy P.T. 
Published: July 2012

The interaction between inositol 1,4,5‐trisphosphate (InsP3) and guanosine 5′‐O‐(3‐thio triphosphate) (GTPγS) releasable calcium (Ca2+) pools was examined using 45Ca effluxes in permeabilized cultured airway smooth muscle cells from rabbit trachea.
Addition of InsP3 or GTPγS caused a concentration‐dependent release of intracellular Ca2+. The release of Ca2+ by InsP3 was much greater than with GTPγS. Pretreatment with maximally effective InsP3 (10 μm) abolished the GTPγS‐induced Ca2+ release, whereas pretreatment with 100 μm GTPγS reduced the InsP3‐induced Ca2+ release by 25%.
Ryanodine (100 μm), also gave a large release of intracellular Ca2+. After pretreatment with 100 μm ryanodine, GTPγS did not induce Ca2+ release, and InsP3‐induced Ca2+ release was reduced by 76%.
Caffeine (50 mm), produced a slow release of intracellular Ca2+. Pre‐exposure to 50 mm caffeine had no effect on the GTPγS‐induced Ca2+ release but reduced the InsP3 releasable Ca2+ by 58%.
Pretreatment with ryanodine abolished the caffeine‐induced Ca2+ release, and addition of caffeine before ryanodine reduced the ryanodine‐induced Ca2+ release by 64.4%.
These results suggest that there are at least three pools of Ca2+ present within airway smooth muscle cells. The largest pool is released by InsP3 or ryanodine, another is released either by a high concentration of InsP3 or on application of GTPγS, and the third by InsP3 alone. Ca2+ may be able to move from the GTPγS‐sensitive pool into the InsP3‐ and ryanodine‐sensitive pool when this becomes depleted. In contrast, the opposite movement of Ca2+ cannot occur.
Three distinct binding sites for [3H]‐prazosin in the rat cerebral cortex
Authors: Oshita Masafumi , Kigoshi Shigeru , Muramatsu Ikunobu 
Published: July 2012

The putative α1‐adrenoceptor subtypes of rat cerebral cortex membranes were characterized in binding experiments with [3H]‐prazosin.
Specific binding of [3H]‐prazosin was saturable between 20–5000 pm. Scatchard plots of the binding data were non‐linear, indicating the presence of two distinct affinity sites for prazosin (pKD, high = 10.18, Rhigh = 308 fmol mg−1 protein; pKD, low = 8.96, Rlow = 221 fmol mg−1 protein).
In the membranes pretreated with chlorethylclonidine (CEC) two affinity sites for prazosin were also observed: the affinities were similar to those without CEC pretreatment, but the maximum numbers of binding sites were reduced by CEC pretreatment to 23 and 62% for prazosin‐high (Rhigh) and low affinity sites (Rlow), respectively.
The prazosin‐high affinity sites were further subdivided into two subclasses by WB4101(2‐(2,6‐dimethoxyphenoxyethyl)aminomethyl‐1,4‐benzodioxane) and phentolamine; the low affinity sites for WB4101 and phentolamine were more potently inactivated by CEC as compared with the high affinity sites. On the other hand, prazosin, HV723 (α‐ethyl‐3,4,5‐trimethoxy‐α‐(3‐((2‐(2‐methoxyphenoxy)ethyl)‐amino)‐propyl)benzeneacetonitrile fumarate) and yohimbine inhibited [3H]‐prazosin binding to prazosin‐high affinity sites monophasically.
In addition to the high affinity sites, the prazosin‐low affinity sites were labelled at high concentrations of [3H]‐prazosin. Thus, prazosin and WB4101 showed shallow displacement curves. On the other hand, HV723 and yohimbine did not discriminate between prazosin‐high and low affinity sites.
Two distinct α1‐adrenoceptor subclassifications have been recently proposed (α1A, α1B subtypes and α1H, α1L, α1N subtypes). According to the criteria defined with competitive antagonists in both the subclassifications, the present results indicate that the α1‐adrenoceptors of rat cerebral cortex consist of three different subtypes, presumably α1A, α1B and α1L, and suggest that the α1A and α1B subtypes are identified as a single affinity site for prazosin (α1H). The results also indicate that care must be taken in the use of CEC for α1‐adrenoceptor subclassification because of its low selectivity.
Ca2+ channel activation and membrane depolarization mediated by Cl− channels in response to noradrenaline in vascular myocytes
Authors: Pacaud Pierre , Loirand Gervaise , Baron Anne , Mironneau Chantal , Mironneau Jean 
Published: July 2012

The effects of noradrenaline (NA) were studied on vascular smooth muscle cells isolated from rat portal vein.
Two types of single‐Ca2+ channel currents with conductances of 17 pS and 8 pS were obtained in cell‐attached configuration. Bath application of NA increased the open probability of both channels during depolarizing pulses without a change of background membrane conductance. However, NA did not open Ca2+ channels when the membrane patch potential was held at −50 mV, which is about the resting potential in physiological conditions.
In the whole‐cell configuration, studies of voltage‐dependent Ca2+ channel currents showed that the peak conductance curve was not shifted to more negative potentials by NA.
Measurements of internal Ca2+‐concentration ([Ca2+]i) with Indo‐1 indicated that NA increased [Ca2+]i at a holding potential of −50 mV and evoked a Ca2+‐activated Cl− current. These effects were blocked when heparin was included in the pipette solution.
A Cl− channel blocker without effect on Ca2+ channels (anthracene‐9‐carboxylic acid) inhibited the contractions of portal vein strips induced by NA in a manner similar to that produced by a Ca2+ channel inhibitor (isradipine). The NA‐induced contraction was completely suppressed in the presence of ryanodine which depletes intracellular Ca2+ stores.
The present study suggests that activation of Cl− channels by Ca2+ release produces a membrane depolarization which is a prerequisite for enhanced opening of voltage‐dependent Ca2+ channels in response to NA in venous smooth muscle.;
Endothelium‐independent relaxation of rabbit coronary artery by 17β‐oestradiol in vitro
Authors: Jiang Canwen , Sarrel Philip M. , Lindsay David C. , Poole‐Wilson Philip A. , Collins Peter 
Published: July 2012

We assessed the relaxant effect of 17β‐oestradiol (10−7, 10−6 and 10−5 m) on rabbit isolated coronary arteries precontracted with prostaglandin F2α (3 × 10−6 m), high extracellular potassium (30 mm) and Bay K 8644 (10−6 m) plus high extracellular potassium (15 mm) by measuring isometric tension. 17β‐Oestradiol (10−6 and 10−5 m) induced significant relaxation in coronary arteries from male and female rabbits. No differences were seen between arteries with or without endothelium. There were also no differences between coronary arteries isolated from male and female rabbits.
Inhibitors of endothelium‐derived relaxing factor and vasodilator prostanoids, namely, reduced haemoglobin, Nω‐nitro‐l‐arginine methyl ester and indomethacin, did not affect the relaxation induced by 17β‐oestradiol in endothelium‐intact coronary arteries.
Methylene blue, an inhibitor of guanylate cyclase, did not affect the coronary artery relaxation induced by 17β‐oestradiol.
The calcium concentration‐dependent contraction curve in potassium‐depolarization medium was shifted to the right by 17β‐oestradiol (10−6 and 10−5 m) in the rabbit coronary artery and rat aorta. The −log EC50 s of calcium in control and after incubation with 17β‐oestradiol (10−6 and 10−5 m) were 3.7 ± 0.09, 3.1 ± 0.10 and 2.8 ± 0.08 respectively in rabbit coronary arteries and 3.8 ± 0.11, 3.3 ± 0.14 and 2.9 ±0.15 in rat aorta.
The results indicate that 17β‐oestradiol induces rabbit coronary artery relaxation by an endothelium‐independent mechanism in vitro. A calcium antagonistic property may be involved in the mechanism of rabbit coronary arterial relaxation by 17β‐oestradiol.;
Dexamethasone‐induced gastric mucosal damage in the rat: possible role of platelet‐activating factor
Authors: Filep János G. , Hermán Ferenc , Földes‐Filep Éva , Schneider Ferenc , Braquet Pierre 
Published: July 2012

The aim of the present experiments was to study the possible role of platelet‐activating factor (PAF) in mediating gastric mucosal damage induced by dexamethasone in the rat by measuring gastric tissue levels of PAF during dexamethasone‐treatment and by investigating the effects of specific PAF receptor antagonists on dexamethasone‐induced gastric lesions. PAF‐like bioactivity extracted from the rat glandular stomach was determined by a platelet aggregation assay.
Dexamethasone treatment (0.4– 4 mg kg−1, daily for 1– 6 days) produced time‐ and dose‐dependent damage to the glandular mucosa of the stomach as characterized by extensive, uniform hyperaemia with multiple, focal petechiae and erosions.
These changes were accompanied by a time‐, and dose‐dependent increase in PAF content of the glandular stomach. Control rat stomach contained small amounts of PAF (0.14 ± 0.04 ng per g wet weight), which increased over 40 fold in response to dexamethasone treatment (4 mg kg−1, daily for 6 consecutive days). The presence of PAF‐like material in the stomach extract was ascertained by thin‐layer chromatography, high performance liquid chromatography and by alkaline hydrolysis.
Pretreatment of the animals with one or other of the structurally unrelated PAF receptor antagonists, BN 52021 (10 mg kg−1, i.p.) or BN 50727 (1 mg kg−1, i.p.) significantly reduced dexamethasone‐induced gastric damage. In these animals neither petechiae nor erosions were observed.
These observations suggest that PAF is a likely endogenous mediator of glucocorticoid‐induced gastric mucosal damage in the rat.
α.‐Adrenoceptor modulation of the efferent function of capsaicin‐sensitive sensory neurones in guinea‐pig isolated atria
Authors: Amerini Sandra , Rubino Annalisa , Mantelli Laura , Ledda Fabrizio 
Published: July 2012

Transmural nerve stimulation of guinea‐pig atria, obtained from animals pretreated with reserpine (5 mg kg−1, i.p.), in the presence of atropine 1 μm and of the β‐adrenoceptor blocker CGP 20712A 1 μm, induced a positive inotropic effect which was reduced by the calcitonin gene‐related peptide (CGRP) antagonist hCGRP‐(8–37) and abolished by pretreatment with capsaicin 1 μm.
Noradrenaline concentration‐dependently (0.01– 10 μm) reduced the increase in cardiac contractility induced by transmural nerve stimulation. The inhibitory effect of noradrenaline was antagonized by yohimbine (0.5– 1 μm), in a dose‐dependent manner. Prazosin (0.5–1 μm) antagonized the effect of noradrenaline and this effect was independent of concentration.
In the presence of yohimbine, the lower part of the inhibitory‐response curve for noradrenaline was slightly but significantly shifted by prazosin. A similar degree of antagonism was observed in the presence of 1 μm phenoxybenzamine.
The selective α.2 agonists BHT 920 and clonidine reduced, in the same concentration‐range (0.01–1 μm), the cardiac response to transmural nerve stimulation in a yohimbine‐sensitive fashion.
Phenylephrine (0.1– 100 μm) and methoxamine (1– 300 μm) also induced an inhibitory effect on transmural nerve stimulation. The effect of phenylephrine was antagonized by yohimbine (1 μm) more efficiently than by prazosin (0.5 μm).
These results are in keeping with the presence of inhibitory prejunctional α.2‐adrenoceptors on cardiac sensory nerve endings which modulate the efferent function of capsaicin‐sensitive neurones.
Synergism between the contractile effect of epidermal growth factor and that of des‐Arg9‐bradykinin or of α.‐thrombin in rabbit aortic rings
Authors: deBlois Denis , Drapeau Guy , Petitclerc Eric , Marceau François 
Published: July 2012

Rabbit aortic rings were used to test the possible contractile effects of growth factors and their interaction with other stimuli. A rapid potentiation of kinin‐induced contraction by epidermal growth factor (EGF) has been previously observed in this preparation.
EGF (5–1500 ng ml−1) and the isoform BB of platelet‐derived growth factor (PDGF‐BB; 1–126 ng ml−1) exerted modest but sustained contractile effects in rabbit aortic rings.
EGF pretreatment (100 ng ml−1) potentiated the contractile responses to des‐Arg9‐bradykinin (des‐Arg9‐BK), an agonist of the B1 receptors for kinin found in this preparation, and to human α.‐thrombin but not to several other contractile stimuli. The interaction appeared also relatively selective for the growth factor, because PDGF‐BB pretreatment potentiated neither des‐Arg9‐BK nor α.‐thrombin‐induced contraction.
EGF, applied on a contraction plateau induced by des‐Arg9‐BK or α.‐thrombin, exerted a synergistic contractile effect, with a time course and a half‐maximal concentration for EGF‐induced contraction similar to the ones recorded in resting tissues (between 67 and 220 ng ml−1, depending on the series of experiments).
The direct or synergistic contractile effects of EGF were not modified by the removal of the endothelium or by treatment with indomethacin. However, the tyrosine kinase inhibitors, erbstatin or genistein, inhibited the synergistic effect of EGF with des‐Arg9‐BK. The small direct contractile effect of EGF was significantly reduced by genistein. The synergistic effect of EGF with α.‐thrombin was comparatively more resistant to the tested tyrosine kinase inhibitors.
An inhibitor of the catalytic activity of α.‐thrombin, d‐Phe‐Pro‐Arg‐CH2Cl, prevented the contractile effect of α.‐thrombin in the aortic rings. In this system, a tetradecapeptide derived from a recently cloned α.‐thrombin receptor was a contractile stimulus at and above 10 μm. Consistent with the hypothesis that this peptide could behave as an α.‐thrombin receptor agonist, its contractile effect was potentiated by EGF pretreatment. Pharmacological evidence was provided to show that the receptors for α.‐thrombin were distinct from the B1 receptors for kinins. Together, these findings suggest that a model of a cleavable receptor recently elaborated to account for α.‐thrombin effects on human platelets is valid in blood‐free vascular smooth muscle preparations such as the rabbit isolated aorta.
The synergism between EGF and kinin‐ or α.‐thrombin‐induced contractions constitutes a novel mode of myotropic action for growth factors. The synergism is probably dependent on the tyrosine kinase activity of receptors for EGF. These combinations of stimuli could occur in various types of vascular disease and account for abnormal vascular reactivity often associated with atheroma lesions or vascular wound healing.