bluuebunny/crossref_metadata_2025_split huggingface dataset:
K+‐stimulation of the phosphoinositide pathway in guinea‐pig ileum longitudinal smooth muscle is predominantly neuronal in origin and mediated by the entry of extracellular Ca2+
Authors: Watson Stephen P. , Lai Jeremy , Sasaguri Toshiyuki 
Published: July 2012

K+ and scorpion toxin stimulate formation of inositol phosphates in guinea‐pig ileum longitudinal smooth muscle slices. The response to these two agents is not additive.
The response to K+ is inhibited partially by nifedipine and partially by ω‐conotoxin. When given together the effect of these two Ca2+ channel blockers is additive and the response to K+ is reduced by more than 80%.
The response to scorpion toxin is inhibited completely by tetrodotoxin, partially by ω‐conotoxin but not by atropine or nifedipine. Scorpion toxin induces a similar formation of inositol phosphates in collagenase‐dispersed cells to that seen in cross‐chopped slices.
The responses to scorpion toxin and K+ are inhibited completely when the extracellular Ca2+ concentration is reduced to below cytosolic levels (< 100 nm).
Neither nifedipine nor ω‐conotoxin, either alone or in combination, inhibited formation of inositol phosphates by substance P or carbachol. Both of these agonists induced a significant formation of inositol phosphates even when the extracellular Ca2+ concentration was reduced to 10 nm.
These results indicate that K+ and scorpion toxin induce formation of inositol phosphates through the mobilisation of extracellular Ca2+. The response to K+ appears to occur predominantly in neuronal cells.
Endothelin‐1 inhibits platelet aggregation in vivo: a study with 111indium‐labelled platelets
Authors: Thiemermann Christoph , May Gillian R. , Page Clive P. , Vane John R. 
Published: July 2012

A non‐invasive technique for the scintigraphic determination of 111indium‐labelled platelet aggregation stimulated with submaximal doses of adenosine diphosphate (ADP, 56 μg kg−1 i.v.), collagen (100 μg kg−1 i.v.), platelet‐activating factor (PAF, 0.1 μg kg−1 i.v.) or thrombin (18 iu kg−1 i.v.) was used to investigate the platelet‐inhibitory effects of endothelin 1 (ET‐1) in anaesthetized rabbits in vivo.
ET‐1 (1 nmol kg−1 i.v.) inhibited ADP‐stimulated platelet aggregation in vivo; a maximum inhibition of 78% of the control value was reached at 3 min, with 45% inhibition at 15 min, and a return to control values at 30 min after injection of the peptide.
ET‐1 (1 nmol kg−1 i.v.) inhibited in vivo platelet aggregation in response to collagen or PAF by 86% and 52%, respectively, but had no effect on thrombin‐induced platelet aggregation.
Indomethacin (5 mg kg−1 i.v.) abolished the ET‐1‐induced inhibition of ADP‐stimulated platelet aggregation and significantly potentiated and prolonged the pressor response brought about by ET‐1.
In conclusion, the data demonstrate that ET‐1 potently inhibits platelet aggregation in the anaesthetized rabbit in vivo by releasing a hypotensive and anti‐aggregatory cyclo‐oxygenase product, presumably prostacyclin, into the circulation.
Enhancement by neuropeptide Y (NPY) of the dihydropyridine‐sensitive component of the response to α1‐adrenoceptor stimulation in rat isolated mesenteric arterioles
Authors: Andriantsitohaina Ramaroson , Stoclet Jean Claude 
Published: July 2012

The mechanism by which neuropeptide Y (NPY) potentiates the vasoconstriction induced by α1‐adrenoceptor agonists was investigated in 3rd generation mesenteric arterioles of the rat.
At a maximally active concentration, nitrendipine (10−6 m) displaced to the right the concentration‐response curves to noradrenaline (pD2 decreased from 6.2 ± 0.06 to 5.7 ± 0.03) and phenylephrine (pD2 decreased from 5.6 ± 0.03 to 5.3 ± 0.03). Diltiazem (10−5 m) also shifted to the right the concentration‐response curve to phenylephrine (pD2 decreased from 6.0 ± 0.06 to 5.5 ± 0.04). In addition, the maximal response to phenylephrine was significantly decreased in the presence of either nitrendipine or diltiazem.
In the absence of a calcium channel blocking agent, NPY (100 nm) produced a leftward shift of the concentration‐response curves to noradrenaline (pD2 increased from 6.2 ± 0.06 to 6.5 ± 0.05) and phenylephrine (pD2 increased from 5.6 ± 0.03 to 6.0 ± 0.06 and from 6.0 ± 0.06 to 6.3 ± 0.11). In the presence of either nitrendipine (10−6 m) or diltiazem (10−5 m), NPY (100 nm) did not alter the concentration‐response curves to either noradrenaline or phenylephrine.
NPY was added to arterioles brought to the same level of tension (40% of the maximal contraction) either by phenylephrine alone (1.5 × 10−6 m) or by a higher concentration of phenylephrine (3 × 10−6 m) followed by the addition of prazosin (1.3 × 10−9 m; a concentration at which it partially blocks α1‐adrenoceptors). In these conditions, the response to phenylephrine was completely abolished by nitrendipine (10−6 m) or by diltiazem (10−5m). Furthermore, NPY (10−10 to 10−7 m) increased the arteriolar tension up to the maximal contractile capacity of the vessels with pD2 values of 8.6 ± 0.02 and 8.7 ± 0.01, in the absence and presence of prazosin, respectively.
Prazosin was replaced in the above protocol by other vasodilator agents acting through different mechanisms. Whether in the presence of 2 × 10−7m forskolin, 6 × 10−7m sodium nitroprusside (which stimulate adenylate cyclase or guanylate cyclase, respectively) or 2 × 10−7m diltiazem (a concentration at which calcium entry is partially blocked), NPY enhanced phenylephrine‐induced contraction to the maximum level with an identical potency (pD2 values of the peptide ranged from 8.3 to 8.7).
The results show that, in rat mesenteric arterioles, NPY potentiates only the calcium entry blocker‐sensitive component of contraction induced by stimulation of α1‐adrenoceptors. In addition, they provide evidence that the peptide counteracts with an equal potency the inhibitory effect of partial block of α1‐adrenoceptors and of relaxing agents acting through different mechanisms. It is suggested that NPY enhances calcium entry induced by stimulation of α1‐adrenoceptors in this tissue.
l‐NG‐nitro arginine (l‐NOARG), a novel, l‐arginine‐reversible inhibitor of endothelium‐dependent vasodilatation in vitro
Authors: Moore P.K. , Al‐Swayeh O.A. , Chong N.W.S. , Evans R.A. , Gibson A. 
Published: July 2012

The effect of l‐NG‐nitro arginine (l‐NOARG) was compared with that of l‐NG‐monomethyl arginine (l‐NMMA) on vasodilatation of the isolated aorta of the rabbit and perfused mesentery of the rat in response to acetylcholine (ACh) and sodium nitroprusside (NP).
l‐NOARG (1.5–100 μm) and l‐NMMA (3–100 μm) produced concentration‐related contraction of the rabbit aorta precontracted with phenylephrine (700–900 nm). Similarly, l‐NOARG (10–200 μm) and l‐NMMA (30–100 μm) elevated perfusion pressure of the noradrenaline (NA, 0.6–2.5 mm)‐preconstricted rat mesentery preparation.
l‐NOARG (1.5–100 μm) and l‐NMMA (3–100 μm) caused concentration‐related inhibition of the vasodilator effect of ACh (0.01–1.0 μm) on the rabbit aorta without influencing responses to NP (0.03–0.5 μm). l‐NOARG methyl ester (30 μm) also inhibited ACh‐induced vasorelaxation with similar potency to NOARG. l‐arginine (30–150 μm) but not d‐arginine (100 μm) caused graded reversal of the inhibitory effect of both l‐NOARG (15 μm) and l‐NMMA (30 μm). Complete reversal of the effect of both inhibitors was achieved with 150 μm l‐arginine. l‐Alanine (50 μm), l‐arginosuccinic acid (5 μm), l‐citrulline (50 μm), l‐methionine (50 μm) and l‐ornithine (50 μm) failed to reverse the inhibitory effect of l‐NOARG (15 μm).
l‐NOARG (10–200 μm) and l‐NMMA (30–100 μm) inhibited the vasodilator effect of ACh (0.006–18.0 nmol) in the rat mesentery without affecting vasodilatation due to NP (1.1–11.1 nmol). l‐Arginine (100 μm) but not d‐arginine (100 μm) produced partial reversal of the effect of l‐NOARG (30 μm) and l‐NMMA (30 μm).
l‐ and d‐Nα‐butyloxycarbonyl NG‐nitro arginine (100 μm) produced modest (approximately 20%) inhibition of the effect of ACh on the rabbit aorta; this effect was not reversible with l‐arginine (100 μm). l‐Nα‐monocarbobenzoxy arginine (l‐NMCA, 50 μm), l‐Nα‐NG‐dicarbobenzoxy arginine (l‐NDCA, 5 μm) and l‐NG‐tosyl arginine (50 μm) were inactive.
These results identify l‐NOARG as a potent, l‐arginine reversible inhibitor of endothelium‐dependent vasodilatation. The available data suggests that l‐NOARG, like l‐NMMA, inhibits endothelial nitric oxide (NO) biosynthesis.
Phenthonium, a quaternary derivative of (−)−hyoscyamine, enhances the spontaneous release of acetylcholine at rat motor nerve terminals
Authors: Fann Meei Liy , Souccar Caden , Lapa Antonio J. 
Published: July 2012

A quaternary derivative of (−)−hyoscyamine, phenthonium (Phen) induced a concentration‐dependent increase in the rate of spontaneous quantal release of acetylcholine (ACh) at the mammalian neuromuscular junction, as shown by intracellular recordings of the miniature endplate potentials (m.e.p.ps) in rat diaphragm muscles.
The prejunctional effect of Phen (10–50 μm) was reversible, unrelated to temperature (22°‐35°C), unaltered by either changes in [Ca2+]o or by high [Mg2+]o, and was not induced by membrane depolarization.
Simultaneously, Phen reduced the amplitude of m.e.p.ps by a postjunctional action.
The muscarinic agonist oxotremorine did not prevent the increase in m.e.p.p. frequency induced by Phen. Cholinesterase inhibition with neostigmine potentiated the prejunctional effect induced by a low (20 μm) but not a high (50 μm) concentration of Phen.
The increase in m.e.p.p. frequency induced by Phen was not influenced by previous incubation with either atropine (0.01–10 μm) or (+)‐tubocurarine (0.05‐0.1 μm). Each antagonist however, intensified the postjunctional effect of Phen.
Phen (20 μm) did not influence the quantal contents of e.p.ps in cut‐muscle preparations or in the presence of high [Mg2+]o. A high concentration of Phen (50 μm) increased the rundown of e.p.p. trains evoked at 10–50 Hz.
The results indicate that the facilitatory prejunctional action of Phen cannot be explained by an antimuscarinic activity. A possible interaction of the antagonist with putative prejunctional nicotinic cholinoceptors however, was not excluded.
Neuropeptide Y neuromodulation of sympathetic co‐transmission in the guinea‐pig vas deferens
Authors: Ellis James L. , Burnstock Geoffrey 
Published: July 2012

We examined the neuromodulatory effects of neuropeptide Y (NPY) on purinergic and adrenergic co‐transmission in the guinea‐pig vas deferens.
In superfused vas deferens preparations, NPY (0.3 μm) inhibited the stimulus‐evoked overflow of both ATP and [3H]‐noradrenaline ([3H]‐NA) at 2 Hz, but only the stimulus‐evoked release of [3H]‐NA at 20 Hz.
Postjunctionally, NPY greatly enhanced responses to α,β‐methylene ATP and to a lesser extent to exogenous NA.
Preparations stimulated in organ baths showed frequency‐dependent contractions to field stimulation. NPY abolished responses to field stimulation at low frequency and a small number of pulses. At high frequency (20 Hz), NPY abolished responses elicited by 10 pulses, inhibited responses by 50% at 20 pulses and had little effect on preparations stimulated for 240 pulses.
Our study suggests that NPY neuromodulates co‐transmission in the vas deferens by inhibiting the release of ATP and NA and that these effects predominate over the postjunctional enhancement by NPY. These results also show that the physiological effect of NPY will be determined both by the frequency at which the nerves are discharging and the duration of their firing.
Cardiovascular effects of central injection of acetylcholine in anaesthetized dogs: a role for vasopressin release
Authors: Rascol Olivier , Montastruc Jean‐Louis , Gauquelin Guillemette , Tran Marie‐Antoinette , Geelen Ghislaine , Gharib Claude , Montastruc Paul 
Published: July 2012

The effect of an intracisternal injection of 20 μg kg−1 of acetylcholine was studied on systolic and diastolic blood pressures, heart rate, and plasma levels of noradrenaline, adrenaline, vasopressin, plasma renin activity and atrial natriuretic factor in chloralose‐anaesthetized dogs, 8 of which were normal and 7 with diabetes insipidus (deprived of vasopressin secretion by surgical lesion of the hypothalamoneurohypophysial system).
Acetylcholine significantly increased systolic and diastolic blood pressures in both groups of animals. However, the rise in blood pressure was significantly shorter lived in the dogs with diabetes insipidus.
Acetylcholine significantly increased plasma levels of noradrenaline but not adrenaline in control animals and in dogs with diabetes insipidus. Noradrenaline and adrenaline responses after acetylcholine were not different in the two groups of animals.
Acetylcholine induced a significant increase in vasopressin plasma levels only in control animals while in dogs with diabetes insipidus vasopressin remained at nearly undetectable levels.
Acetylcholine significantly increased atrial natiuretic factor plasma levels only in control dogs.
Although plasma renin activity increased in both groups of animals after the i.c. injection of acetylcholine, this change was not significant in any group.
These results suggest that, in the anaesthetized dog, the central injection of acetylcholine induces a rise in blood pressure through both an increase in sympathetic outflow and a release of vasopressin.
Effect of capsaicin‐sensitive sensory nerves on plasma glucose and catecholamine levels during 2‐deoxyglucose‐induced stress in conscious rats
Authors: Zhou Xin‐Fu , Livett Bruce G. 
Published: July 2012

Sensory fibres innervate the adrenal medulla but their function is not known. In this paper we have studied the effect of capsaicin‐sensitive sensory fibres on the adrenal catecholamine (CA) response and blood glucose response to 2‐deoxyglucose (2‐DG)‐induced glucopenic stress in conscious rats.
2‐DG at 500 mg kg−1 (i.v.) induced a 2.5 fold increase in plasma glucose levels, a 3.5 fold increase in inferior vena caval (i.v.c.) plasma noradrenaline (NA) levels and a 7 fold increase in i.v.c. plasma adrenaline (Ad) levels over 60 min. The hyperglycaemia in response to 2‐DG was attenuated by pentolinium and by left splanchnicotomy plus right adrenalectomy. These procedures also caused a complete inhibition of the increase in plasma CA.
The hyperglycaemia in response to 2‐DG was attenuated by pretreatment of rats with capsaicin as neonates, suggesting that capsaicin‐sensitive sensory fibres are required for regulation of plasma glucose in response to glucopenic stress.
The increase in i.v.c. plasma CA levels in response to 2‐DG during the early phase of glucopenia (first 30 min) in the conscious rats pretreated with capsaicin was the same as in the rats pretreated with vehicle alone. During the later phase of glucopenia (after 45 min), the increase in plasma CA levels in rats pretreated with capsaicin was higher than in the rats pretreated with vehicle alone.
In vehicle‐pretreated rats and capsaicin‐pretreated rats the tissue NA and Ad levels in the adrenal medulla after 8 h of stress were depleted to the same extent. However, tissue CA levels in the capsaicin group recovered faster over 24 h than in the vehicle group.
These results indicate that capsaicin‐sensitive sensory fibres are not required to maintain adrenal CA secretion during glucopenic stress in the conscious rat but are required for maintenance of blood glucose levels.
Inhibition by ibudilast of leukotriene D4‐induced formation of inositol phosphates in guinea‐pig lung
Authors: Etoh Susumu , Ohashi Mitsuo , Baba Akemichi , Iwata Heitaroh 
Published: July 2012

The effects of a novel anti‐asthmatic drug, 3‐isobutyryl‐2‐ isopropylpyrazolo [1,5‐a]pyridine (ibudilast, KC‐404) on leukotriene D4 (LTD4)‐induced formation of inositol phosphates were studied in slices of guinea‐pig lung and hippocampus.
In guinea‐pig lung, ibudilast inhibited LTD4 (0.01‐1 μm)‐induced formation of inositol monophosphate (IP1) in a concentration‐dependent manner (IC50 = 10 μm) without affecting LTD4 receptor binding.
Ibudilast (10 μm) inhibited histamine (0.1‐1 mm)‐induced formation of IP1 in guinea‐pig lung slices but not in hippocampal slices.
Inhibition of agonist‐induced formation of IP1 by ibudilast was non‐competitive.
Ibudilast had no effect on either GTP‐ or calcium‐stimulated phosphatidylinositol specific‐phospholipase C activity of lung membranes.
These results suggest that ibudilast has no direct effect on LTD4 receptors, GTP binding proteins (G proteins) or phospholipase C, but inhibits inositol phosphate formation, possibly by interfering with the coupling between receptors and G proteins.
Action of cromakalim on potassium membrane conductance in isolated heart myocytes of frog
Authors: Pilsudski Richard , Rougier Oger , Tourneur Yves 
Published: July 2012

The effects of cromakalim on membrane currents were studied at 20°C in frog atrial and ventricular cells in patch clamp recording using the whole cell configuration.
When cromakalim (1 μm) was applied in the external medium, a time‐independent current was activated in a few minutes. Cromakalim induced a weak increase of inward membrane currents recorded during hyperpolarization and a large increase of outward membrane currents recorded during depolarization.
The current voltage relationship of the cromakalim‐induced current reversed near EK and rectified in the outward direction.
The cromakalim‐activated current was inhibited by external application of cesium (20 mm), barium (1.8 mm), tolbutamide (1 mm) and glibenclamide (1 μm).
The effects of cromakalim were insensitive to a cytosolic increase in adenosine 5′‐triphosphate (ATP, 3–5 mm). Cromakalim had no effects when applied in the cell.
Our results confirm that cromakalim activates an IK(ATP)‐like conductance and suggest that the effects of the drug are due to an action on the external side of the membrane and are independent of the ATP cell content.
The properties of the ATP‐induced depolarization and current in single cells isolated from the guinea‐pig urinary bladder
Authors: Inoue R. , Brading A.F. 
Published: July 2012

The actions of exogenously applied ATP were investigated with the whole‐cell patch clamp method in single cells isolated from guinea‐pig urinary bladder with a modified concentration jump technique.
Rapid application of ATP (threshold ca. 100 nm) depolarized the cell membrane with superimposition of action potentials which was followed by transient hyperpolarization. In the presence of D600, the amplitude of the ATP‐induced depolarization was a function of the ATP concentration (EC50:0.5‐1 μm).
ATP activated a dose‐dependent inward current with a short latency (18 ms with 10 μm ATP; measured as the time between the start of application and 10% of the peak). The relationship of the peak current versus ATP concentration was well fitted by a Michaelis‐Menten equation with a Hill coefficient (n) of 1.7 and a dissociation constant (Kd) of 2.3 μm. The current desensitized rapidly and the time course of desensitization was a function of the ATP concentration and could be fitted by two exponentials.
The reversal potential of the ATP‐activated current was near 0 mV. Replacement of extracellular Na by other monovalent or divalent cations indicated that the current flows through nonselective cation channels.
α,β‐Methylene ATP also produced a dose‐dependent inward current but was less potent than ATP (n: 1.6, Kd: 10.4 μm). α,β‐Methylene ATP blocked the response to ATP by desensitization of the receptor.
α,β‐Methylene ATP was 50–100 times more potent than ATP at eliciting a contractile response of strips of detrusor smooth muscle.
The relevance of the above results to the possible role of ATP as the fast excitatory transmitter is discussed.
Bicuculline blocks nicotinic acetylcholine response in isolated intermediate lobe cells of the pig
Authors: Zhang Zhong‐Wei , Feltz Paul 
Published: July 2012

The effect of bicuculline on nicotinic acetylcholine (ACh) responses in isolated intermediate lobe (IL) cells of the pig was investigated by use of patch‐clamp techniques. Bicuculline was found to reduce AChevoked whole‐cell currents (IACh) in all cells tested (n = 40).
The blocking effect of bicuculline on IACh was dose‐dependent, the concentration producing half‐maximal blockade being 43.8 μm.
The blockade of IACh by bicuculline was not voltage‐dependent at membrane potentials above −60 mV, but a slight voltage‐dependence was observed at holding potentials (HP) of −80 and −100 mV.
The inhibitory effect of bicuculline on IACh was partially competitive at a HP of −60 mV.
Neither SR 95531, a pyridazinyl γ‐aminobutyric acid derivative, nor t‐butylbicyclophosphorothionate (TBPS) blocked IACh in IL cells.
It is concluded that bicuculline interacts directly with the ACh receptor‐ionophore complex on porcine IL cells.
Identification of N‐iminoethyl‐l‐ornithine as an irreversible inhibitor of nitric oxide synthase in phagocytic cells
Authors: McCall T.B. , Feelisch M. , Palmer R.M.J. , Moncada S. 
Published: July 2012

The synthesis of nitric oxide (NO) from l‐arginine by rat peritoneal neutrophils (PMN) and the murine macrophage cell‐line J774 and the inhibition of this synthesis by N‐iminoethyl‐l‐ornithine (l‐NIO), NG‐monomethyl‐l‐arginine (l‐NMMA), NG‐nitro‐l‐arginine (l‐NNA) and its methyl ester (l‐NAME) were investigated.
l‐NIO was the most potent inhibitor in both types of cells while l‐NMMA was less active. l‐NNA and l‐NAME had no significant effect in PMN and l‐NNA produced only approximately 40% inhibition of the generation of NO in the J774 cells at the highest concentration tested (300 μm).
The inhibitory effect of l‐NIO was rapid in onset, requiring 10 min pre‐incubation to achieve its full inhibitory activity, while the other compounds required 20–60 min pre‐incubation to achieve their full effect.
The inhibitory effect of l‐NIO (10 μm) on intact cells could not be reversed by l‐arginine (300 μm) but could be prevented by concomitant incubation with this compound (300 μm), while the effect of the other inhibitors could be reversed by a 3–5 fold molar excess of l‐arginine.
The NO synthase from both PMN and J774 cells was cytosolic and NADPH‐ but not Ca2+‐dependent, with Km values for l‐arginine of 3.3 ± 0.8 and 4.2 ± 1.1 μm respectively.
l‐NIO was the most potent inhibitor of the neutrophil and J774 enzymes with IC50 values of 0.8 ± 0.1 and 3 ± 0.5 μm respectively. Furthermore, the effect of l‐NIO was irreversible. The other three compounds were less potent, reversible inhibitors.
The inhibitory effects of all these compounds were enantiomerically specific.
These data indicate that l‐NIO is a novel, potent, rapid in onset and irreversible inhibitor of NO synthase in phagocytic cells. The rapid uptake of l‐NIO compared with the other compounds indicates that phagocytic cells have different uptake mechanisms for l‐arginine analogues.