bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Na+ ‐K+ pump activity by divalent cations in intact peritoneal mast cells of the rat
Authors: Knudsen Trorben , Berthelsen Henrik C. , Johansen Torben 
Published: July 2012

The inhibition by the divalent cations magnesium, barium and strontium and the trivalent ion lanthanum of the Na+‐K+ pump in the plasma membrane of rat peritoneal mast cells was studied in pure mast cell populations by measurement of the ouabain‐sensitive uptake of the radioactive potassium analogue, 86rubidium (86Rb+).
Exposure of the cells to magnesium induced a time‐ and concentration‐dependent decrease in the ouabain‐sensitive K+(86Rb+)‐uptake of the cells without influencing the ouabain‐resistant uptake. The time‐dependent decrease was apparent after incubation of the cells for 10 min or more, but no decrease was observed after 2 min incubation when the cells are supposed to be loaded with sodium due to the cell isolation procedure.
Barium and strontium caused concentration‐dependent decreases in the ouabain‐sensitive K+‐(86Rb+) ‐uptake of the cells but the ouabain‐resistant uptake was not changed. Half maximum decrease in the ouabain‐sensitive K+(86Rb+)‐uptake was observed with 1.8 mm magnesium, 1.2 mm barium and 0.7 mm strontium.
The trivalent ion lanthanum blocked almost completely the ouabain‐sensitive K+(86Rb+)‐uptake at a concentration of 1 μm as does 1 mm calcium. Combining either of these ions with magnesium had no further inhibitory effect on the ouabain‐sensitive uptake.
In conclusion, in addition to the previously suggested modulation by calcium of the activity of the Na+‐K+ pump, evidence is provided in this investigation that the modulation may be a more general effect of divalent and polyvalent cations present in the extracellular space through their influence on the sodium permeability of the plasma membrane.
Endogenous nitric oxide as a modulator of rabbit skeletal muscle microcirculation in vivo
Authors: Persson M.G. , Gustafsson L.E. , Wikludn N.P. , Hedqvist P. , Moncada S. 
Published: July 2012

Intravital microscopy of rabbit tenuissimus muscle microvasculature was used for in vivo studies of the role of endogenous nitric oxide (NO) in local vascular control. Derivatives of arginine were applied topically in order to modulate the formation of NO from l‐arginine.
l‐NG‐monomethylarginine (l‐NMMA) (10–100 μm), but not d‐NG‐monomethylarginine (d‐NMMA), dose‐dependently reduced microvascular diameters. The vasoconstriction induced by l‐NMMA (100 μm) was prevented by pretreatment with l‐arginine (1 mm) but not with d‐arginine (1 mm). Intravenous infusions of l‐arginine (300 mg kg−1) reversed the effect of l‐NMMA (100 μm). l‐Arginine or d‐arginine applied topically at 1 mm per se had no effect on microvascular diameters.
Vasodilatation by acetylcholine (0.03‐3 μm) was significantly inhibited by l‐NMMA (100 μm), whereas vasodilatation by adenosine (0.1–100 μm) or sodium nitroprusside (100 nm) was not affected.
The hyperaemic response after tenuissimus muscle contractions induced by motor nerve stimulation was unaffected by the presence of l‐NMMA (100 μm).
Aggregates of platelets and white blood cells were seen in venules during superfusion with l‐NMMA (100 μm), but not with d‐NMMA (100 μm).
Our results suggest that endogenous NO formed from l‐arginine is a modulator of microvascular tone and platelet and white cell‐vessel wall interaction in vivo. Nitric oxide does not, however, appear to play a role in the mediation of functional hyperaemia in this tissue.
Effects of butanedione monoxime on neuromuscular transmission
Authors: Gage P.W. , McArdle J.J. , Saint D.A. 
Published: July 2012

The amplitude of endplate potentials was increased by concentrations of butanedione monoxime (BDM, 5–20 mm) that typically caused muscle paralysis.
Although BDM slowed the decay of spontaneous miniature endplate currents, the effect was insuffient to explain most of the large increase in amplitude of endplate potentials.
The quantal content of endplate potentials was increased by BDM in a reversible, concentration‐dependent manner.
The frequency of miniature endplate potentials was not changed by 10 mm BDM in the presence of normal or raised potassium concentrations, indicating that BDM does not change quantal content by a direct effect on calcium channels or on steady‐state intracellular calcium concentration.
A change in the time course of the extracellularly recorded nerve terminal action potential caused by BDM was similar to the change produced by 4‐aminopyridine (4‐AP).
The increase in quantal content produced by BDM was only slightly reduced in the presence of 1 mm tetraethylammonium (TEA) but was significantly reduced in the presence of 0.5 to 1 mm 4‐AP.
It was concluded that BDM blocks a 4‐AP‐sensitive potassium conductance in motor nerve terminals and, by increasing the duration of the action potential in this way, increases evoked transmitter release.
Bradykinin induces elevations of cytosolic calcium through mobilisation of intracellular and extracellular pools in bovine aortic endothelial cells
Authors: Buchan Kevin W. , Martin William 
Published: July 2012

In the presence of 1.8 mm extracellular calcium, bradykinin (0.3 nm–100 nm) induced a biphasic elevation of intracellular calcium ([Ca2+]i) in bovine aortic endothelial cells, consisting of an initial, large transient component followed by a lower sustained component.
When endothelial cells were bathed in nominally calcium‐free solution containing 0.5 mm EGTA, bradykinin induced only a transient elevation of [Ca2+]i: the magnitude of this was significantly smaller than that obtained in the presence of extracellular calcium and the sustained phase was abolished. In the continued presence of bradykinin, re‐addition of extracellular calcium to achieve a level of around 1.8 mm resulted in the induction of a biphasic elevation of [Ca2+]i consisting of a large initial component followed by a lower sustained component.
In the presence of 1.8 mm extracellular calcium, caffeine (5 mm) induced a small elevation of [Ca2+]i. When endothelial cells were bathed in nominally calcium‐free solution containing 0.5 mm EGTA, the caffeine‐induced elevation of [Ca2+]i was almost completely abolished.
In the presence of 1.8 mm extracellular calcium, treatment of endothelial cells with the calcium influx blocker, nickel chloride (4 mm), had no effect on resting [Ca2+]i or on the magnitude of the bradykinin‐induced initial transient elevation of [Ca2+]i but abolished the sustained component.
In the presence of 1 mm extracellular calcium, treatment with the calcium chelator EGTA (2 mm; 1 min) had no effect on resting [Ca2+]i but the magnitude of the bradykinin‐induced initial transient elevation of [Ca2+]i was significantly reduced. Increasing the exposure time or concentration of EGTA resulted in no further reduction in the magnitude of the bradykinin‐induced transient component.
Treatment of endothelial cells with the putative inhibitor of intracellular calcium release, 3,4,5‐trimethoxybenzoic acid 8‐(diethylamino)octyl ester (TMB‐8, 0.1 mm) increased resting [Ca2+]i slightly but had no effect on the magnitude of the bradykinin‐stimulated elevation of [Ca2+]i.
These findings suggest that, in bovine aortic endothelial cells, the bradykinin‐induced initial transient elevation of [Ca2+]i is completely dependent upon release of calcium from intracellular stores and the sustained component is due to calcium influx. They further suggest the possible existence of two intracellular calcium pools, one which is rapidly depleted in the absence of extracellular calcium and a second which is resistant to such depletion.
The effects of calcitonin gene‐related peptide on submucosal gland secretion and epithelial albumin transport in the ferret trachea in vitro
Authors: Webber S.E. , Lim J.C.S. , Widdicombe J.G. 
Published: July 2012

We have examined the effect of calcitonin gene‐related peptide (CGRP) on basal mucus volume, lysozyme and albumin outputs from the ferret whole trachea in vitro, and on the outputs produced by methacholine and substance P (SP). We have also examined the effect of inhibiting neutral enkephalinase with thiorphan on the responses to CGRP.
CGRP (1–100 nm) produced small concentration‐dependent increases in basal mucus volume, lysozyme and albumin outputs. These effects of CGRP were enhanced by thiorphan. The increases in basal outputs with CGRP and the potentiation by thiorphan were considerably less than previously observed with SP and neurokinin A (NKA). CGRP had no significant effect on potential difference (PD) across the trachea.
CGRP produced a concentration‐dependent inhibition of methacholine‐ and SP‐induced lysozyme output but a concentration‐dependent increase in methacholine‐ and SP‐induced albumin output. The effects of CGRP on methacholine‐induced lysozyme and albumin outputs were enhanced by thiorphan. CGRP weakly inhibited methacholine‐induced mucus volume output and weakly enhanced SP‐induced mucus volume output.
Thus, CGRP weakly stimulates basal serous cell secretion and epithelial albumin transport, but does not alter epithelial integrity. CGRP inhibits the serous cell secretion due to methacholine or SP, but potentiates the epithelial albumin transport produced by these agents. The interaction between CGRP and other sensory neuropeptides or muscarinic agonists on airway submucosal glands and epithelium may be important in the normal airway and in inflammatory airway diseases where release of sensory neuropeptides is enhanced.
Comparison of the effects of neuropeptide Y and noradrenaline on rat gastric mucosal blood flow and integrity
Authors: Tepperman B.L. , Whittle B.J.R. 
Published: July 2012

The effects of neuropeptide Y (NPY) and noradrenaline on rat gastric mucosal blood flow, as estimated by laser Doppler flowmetry (LDF), have been examined. In addition, the ability of NPY and noradrenaline to induce acute mucosal haemorrhagic damage has also been assessed.
Close‐arterial infusion of NPY (0.05–0.2 nmol kg−1 min−1) for 10 min in the anaesthetized rat induced a dose‐dependent fall in LDF, but had minimal effects on systemic arterial blood pressure. Higher doses of NPY did not produce any further reduction in LDF.
Close‐arterial infusion (0.1–0.4 nmol kg−1 min−1) of the structurally related peptide YY (PYY) or pancreatic polypeptide (PP), had inconsistent actions in decreasing LDF.
Close‐arterial infusion of noradrenaline (30–90 nmol kg−1 min−1) dose‐dependently reduced gastric LDF.
Local infusion of NPY (0.1 and 0.2 nmol kg−1 min−1) or noradrenaline (45 and 60 nmol kg−1 min−1) resulted in dose‐related increases in the area of mucosal hemorrhagic damage.
Pretreatment with the α1‐adrenoceptor antagonist, prazosin (0.1 mg kg−1, i.v.) significantly reduced the effect of noradrenaline, but not NPY, on both LDF and mucosal damage.
These findings indicate that NPY and noradrenaline act directly on the gastric microvasculature to induce vasoconstriction and both can induce acute mucosal damage. Therefore endogenous NPY, like noradrenaline could play a modulatory role in regulating vascular tone and may influence mucosal integrity.
Prejunctional nicotinic receptors involved in facilitation of stimulation‐evoked noradrenaline release from the vas deferens of the guinea‐pig
Authors: Todorov L. , Windisch K. , Shersen H. , Lajtha A. , Papasova M. , Vizi E.S. 
Published: July 2012

In guinea‐pig prostatic vas deferens loaded with [3H]‐noradrenaline ([3H]‐NA), nicotinic receptor agonists, nicotine and dimethylphenylpiperazinium (DMPP) enhanced the resting and facilitated the stimulation‐evoked release of [3H]‐NA in a concentration‐dependent fashion. The effect of nicotine on both contraction of vas deferens and release of NA in response to field stimulation was stereospecific in favour of the naturally occurring (−)‐enantiomer. Prolonged (15 min) exposure to (−)‐nicotine resulted in a cessation of the facilitatory effect on NA release and on responses of the vas deferens to field stimulation.
The rank order of agonist potency in facilitating NA release was DMPP = (−)‐nicotine > (+)‐nicotine. Cytisine had no agonistic activity. The dissociation constants (KD) of antagonists were 9.3 ± 0.6 and 31.4 + 2.4 μm for (+)‐tubocurarine and hexamethonium, respectively, when (−)‐nicotine was used as agonist. α‐Bungarotoxin had no antagonistic activity. These findings suggest that nicotinic receptors located on noradrenergic axon terminals are different from those located postsynaptically in striated muscle or ganglia but seem similar to those present on cholinergic axon terminals at the neuromuscular junction.
Cotinine, the breakdown product of nicotine failed to have any agonistic activity indicating that nicotine itself is responsible for the effects observed on axon terminals.
Stimulation of presynaptic muscarinic receptors by oxotremorine prevented the nicotine‐induced facilitation of [3H]‐NA release, indicating the presence of both inhibitory muscarinic and facilitatory nicotinic receptors on noradrenergic axon terminals.
Vascular 5‐HT1‐like receptors that mediate contraction of the dog isolated saphenous vein and carotid arterial vasoconstriction in anaesthetized dogs are not of the 5‐HT1A or 5‐HT1D subtype
Authors: Perren Marion J. , Feniuk Wasyl , Humphrey Patrick P.A. 
Published: July 2012

There is controversy about whether 5‐HT1A receptors mediate contraction of isolated cerebral blood vessels. We have therefore compared the vascular actions of the 5‐HT1A receptor agonist, 8‐hydroxy‐2‐(di‐n‐propyl‐amino)‐tetralin (8‐OH‐DPAT) with those of the 5‐HT1‐like receptor agonist, sumatriptan, on the dog isolated saphenous vein, which contains a 5‐HT1‐like receptor similar to those on cerebral blood vessels, and in the carotid circulation of the anaesthetized dog.
5‐Hydroxytryptamine (5‐HT), sumatriptan and 8‐OH‐DPAT each caused contraction of dog isolated saphenous vein with a rank order of agonist potency of 5‐HT > sumatriptan > 8‐OH‐DPAT and EC50 values (95% confidence limits) of 0.06 (0.04–0.08), 0.3 (0.1–0.8) and 3.9 (2.0–7.5) μm respectively. The maximum contractile effect produced by each agonist was similar.
The contractile effects of 5‐HT, sumatriptan and 8‐OH‐DPAT in the dog isolated saphenous vein were resistant to antagonism by the 5‐HT1A receptor antagonists spiperone, spiroxatrine and pindolol (all 1 μm). The 5‐HT1D receptor ligands, metergoline (0.1 μm) rauwolscine (1 μm) and yohimbine (1 μm) had little or no antagonist activity. In contrast, the non‐selective 5‐HT1‐like receptor blocking drug, methiothepin (0.03–0.3 μm) potently antagonized the contractile effects of 5‐HT, sumatriptan and 8‐OH‐DPAT to a similar degree, suggesting that all three agonists act at the same receptor.
In ganglion‐blocked, anaesthetized dogs, intra‐carotid administration of 8‐OH‐DPAT (0.3–3 μg kg−1) and sumatriptan (0.1–1 μg kg−1), caused dose‐dependent carotid arterial vasoconstriction. The two agonists were approximately equipotent in this respect.
The carotid arterial vasoconstrictor actions of 8‐OH‐DPAT and sumatriptan were not modified by spiperone (1 mg kg−1, i.v.) but were antagonized to a similar extent by the subsequent administration of methiothepin (1 mg kg−1, i.v.).
These results suggest that 8‐OH‐DPAT contracts the dog isolated saphenous vein and constricts the carotid arterial circulation of anaesthetized dogs by activation of 5‐HT1‐like receptors which are not of the 5‐HT1A subtype, nor, on the basis of data with metergoline in the dog isolated saphenous vein, of the 5‐HT1D subtype. The receptor involved in these actions appears to be the same as that mediating the vasoconstrictor effects of sumatriptan. This receptor does not appear to be like any known 5‐HT1 ligand binding site; hence the current description, 5‐HT1‐like, remains the most appropriate.
Dicentrine, a natural vascular α1‐adrenoceptor antagonist, isolated from Lindera megaphylla
Authors: Teng Che‐Ming , Yu Sheu‐Meei , Ko Feng‐Nien , Chen Chien‐Chih , Huang Yu‐Ling , Huang Tur‐Fu 
Published: July 2012

The pharmacological activity of dicentrine, isolated from Lindera megaphylla, was determind in rat isolated thoracic aorta, guinea‐pig isolated trachea and human platelet‐rich plasma.
Dicentrine was found to be a potent α1‐adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of noradrenaline‐ (pA2 = 8.19 ± 0.09) or phenylephrine (pA2 = 9.01 ± 0.10)‐induced vasoconstriction. These effects still persisted in denuded aorta. It was less potent than prazosin (pA2 = 10.60 ± 0.10), but was more potent than phentolamine (pA2 = 7.53 ±0.10) or yohimbine (pA2 = 6.20 ± 0.05).
Inositol monophosphate formation induced by noradrenaline (3 μm) in rat thoracic aorta was suppressed by dicentrine (3–10 μm) and prazosin (3 μm).
A high concentration of dicentrine (30 μm) did not affect the aortic contraction induced by the thromboxane receptor agonist U‐46619 (1 μm), angiotensin II (1 μm), high potassium (60 mm) or carbachol (3 μm).
Contraction of guinea‐pig trachea caused by histamine or carbachol was slightly inhibited by dicentrine (30 μm), while β‐adrenoceptor relaxation to isoprenaline in trachea was not affected.
Aggregation in human platelet‐rich plasma induced by adrenaline (10 μm) was blocked by yohimbine (5 μm). A high concentration of dicentrine (> 30 μm) caused slight inhibition of aggregation, the release reaction and thromboxane formation. Complete blockade was obtained with 150 μm dicentrine.
It is concluded that dicentrine is a potent, selective α1‐adrenoceptor antagonist in vascular smooth muscle.
Direct effects of adenylyl 5′‐(β,γ‐methylene)diphosphonate, a stable ATP analogue, on relaxant P1‐purinoceptors in smooth muscle
Authors: Hourani S.M.O. , Bailey S.J. , Nicholls J. , Kitchen I. 
Published: July 2012

Previous results obtained with the rat colon muscularis mucosae, which contracts in response to adenosine and adenosine 5′‐triphosphate (ATP), had suggested that adenylyl 5′‐(β,γ‐methylene)diphosphonate (AMPPCP), a stable ATP analogue, acted on P1‐purinoceptors rather than, as expected, on P2‐purinoceptors. This possibility has been examined in two tissues in which adenosine and ATP both cause relaxation, the guinea‐pig taenia caeci and the rat duodenum.
ATP, 2‐methylthio‐ATP (2‐MeSATP), AMPPCP, adenosine 5′‐(α,β‐methylene)triphosphonate (AMPCPP) and adenosine each relaxed the taenia caeci and the duodenum, and the order of potency of the nucleotides in each tissue was 2‐MeSATP > ATP > AMPCPP > AMPPCP, indicating that these effects were mediated by P2Y‐purinoceptors.
The P1 antagonist 8‐(p‐sulphophenyl)theophylline (8‐SPT) (100 μm) did not affect the responses to ATP, 2‐MeSATP or AMPCPP in either tissue, but inhibited the responses of adenosine and of AMPPCP in both tissues. In the duodenum a lower concentration of 8‐SPT caused a parallel shift to the right of the concentration‐response curve to adenosine and to AMPPCP but to different extents, with AMPPCP being inhibited more powerfully than adenosine. A dose‐ratio of around 5 was observed for adenosine and AMPPCP at concentrations of 8‐SPT of 20 μm and 2 μm respectively, but Schild analysis resulted in plots with slopes greater than unity. In the taenia caeci, however, 8‐SPT inhibited adenosine more powerfully than AMPPCP, and a range of concentrations (10–20 μm) only caused a two fold shift in the concentration‐response curve for AMPPCP, although the concentration‐response curve to adenosine was shifted in a concentration‐dependent manner and Schild analysis gave a pA2 value of 5.13 with a slope of 0.90.
As has been shown in other tissues, including the guinea‐pig taenia caeci, ATP (100 μm) was rapidly dephosphorylated by enzymes present in the rat duodenum, with less than 10% remaining after 20 min incubation, whereas AMPPCP (100 μm) was resistant to degradation, with greater than 90% remaining at the same time point.
AMPPCP therefore has pronounced but variable agonist actions on P1‐purinoceptors, and appears to act entirely via these receptors on the rat duodenum although in the guinea‐pig taenia caeci this action is less important and it acts largely via P2Y‐purinoceptors. These P1‐purinoceptor effects of AMPPCP are direct and are not due to its degradation to adenosine.
Characterization of endothelin receptors on a human neuroblastoma cell line: evidence for the ETA subtype
Authors: Wilkes Lesley C. , Boarder Michael R. 
Published: July 2012

Specific binding sites for synthetic endothelin (ET) isoforms were studied on intact cells of the SK‐N‐MC cell line, derived from a human neuroblastoma.
[125I]‐ET‐1 (2.5 × 10−11 m) specifically bound to a single class of binding sites on these cells (Hill coefficient of 1.06 ± 0.04, n = 3) with an apparent Kd of 1.4 ± 0.3 × 10−9 m and a Bmax of 3.1 ± 1.0 pmol mg−1 protein. [125I]‐ET‐3 (2.5 × 10−11 m), did not specifically bind to SK‐N‐MC cells.
The binding of [125I]‐ET‐1 was competitively inhibited by other ET isoforms, the order of potency being ET‐1 > sarafotoxin S6b > ET‐3.
Association of 1 nm [125I]‐ET‐1 at 37°C reached apparent equilibrium at 60–80 min, with half‐maximal binding being achieved at 12 min.
Dissociation was measured after both 10 min and 60 min of association with 64% and 30% respectively of specifically bound [125I]‐ET‐1 dissociating. The actual amounts of [125I]‐ET‐1 dissociated were similar in both cases.
Incubation of [125I]‐ET‐3 with SK‐N‐MC cells at 37°C for 60 min did not result in significant degradation of this peptide. However, [125I]‐ET‐1 was broken down by incubation with SK‐N‐MC cells, the pattern of degradation of dissociable [125I]‐ET‐1 (and that found in the supernatant) being different from that of non‐dissociable [125I]‐ET‐1.
ET‐1 concentration‐dependently induced an increase in total inositol phosphate accumulation in sub‐confluent (but not in confluent) cultures of SK‐N‐MC cells (EC50 = 6.43 ± 1.9 × 10−10 m). ET‐3 was without effect.
These results show that ET‐1 specifically binds to SK‐N‐MC cells with the characteristics of an ETA receptor. Our earlier finding that adrenal chromaffin cells express an ETB receptor indicates the existence of multiple ET receptor types on neuronal cells.