bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelium‐dependent relaxation by substance P in human isolated omental arteries and veins: relative contribution of prostanoids, nitric oxide and hyperpolarization
Authors: Wallerstedt Susanna M , Bodelsson Mikael 
Published: August 2006

The objective of the present study was to investigate human omental arteries and veins with respect to: (i) the contractile effect of the thromboxane A2 analogue U46619, (ii) endothelium‐dependency and mediators of the relaxing effect of substance P (SP) and acetylcholine (ACh).
Changes in isometric tension in response to administration of U46619, SP and ACh were measured in human isolated omental arteries and veins with and without endothelium. To investigate the mechanism of action of SP, the SP‐induced relaxation was measured in the presence of indomethacin (cyclo‐oxygenase inhibitor), NG‐monomethyl‐l‐arginine (l‐NMMA, nitric oxide‐synthase inhibitor), KCl (inhibitor of endothelium‐dependent hyperpolarization), tetraethylammonium (TEA; non‐selective inhibitor of K+‐channels, with some preference for the high conductance Ca2+‐activated K+‐channel, BKCa), glibenclamide (inhibitor of the ATP‐sensitive K+‐channel) and/or clotrimazole (inhibitor of the cytochrome P450‐system and the intermediate conductance Ca2+‐activated K+‐channel, IKCa).
U46619 contracted both the artery and the vein segments. Endothelium removal did not alter the contraction.
ACh caused neither contraction nor relaxation in artery and vein segments precontracted with U46619.
In both artery and vein segments precontracted with U46619, SP produced endothelium‐dependent relaxation. The relaxation was unaffected by indomethacin, but was incompletely reduced by l‐NMMA and KCl respectively. The l‐NMMA‐resistent relaxation was abolished in the presence of KCl.
TEA inhibited the SP‐induced relaxation in artery and vein segments both in the presence and absence of l‐NMMA and indomethacin, while glibenclamide and clotrimazole had no effect.
In conclusion, the SP‐induced relaxation in human omental arteries and veins seems to be mediated via NO and endothelium‐dependent hyperpolarization. KATP and IKCa are probably not involved in the hyperpolarization, but activation of BKCa may contribute to the hyperpolarization. Prostanoid synthesis and the cytochrome P450‐system are probably not involved in the SP‐induced relaxation in this area.

British Journal of Pharmacology (1997) 120, 25–30; doi:10.1038/sj.bjp.0700879
α‐Latrotoxin‐induced transmitter release in feline oesophageal smooth muscle: focus on nitric oxide and vasoactive intestinal peptide
Authors: Ny Lars , Waldeck Kristian , Carlemalm Eric , Andersson Karl‐Erik 
Published: August 2006

The effects of α‐latrotoxin (αLTX) on muscle tone, resting membrane potential, cyclic nucleotide content, and ultrastructure were examined in feline oesophageal smooth muscle, including the lower oesophageal sphincter (LOS).
In circular smooth muscle strips from LOS developing active tone, αLTX (1 nm) induced a 94±3% (n=16) relaxation. Intermittent treatment with αLTX for 4 h abolished the response. Pretreatment with NG‐nitro‐l‐arginine (l‐NOARG; 0.1 mm) attenuated the relaxation.
In carbachol‐contracted circular smooth muscle strips from the LOS and oesophageal body (OB), αLTX induced a 95±5% (n=6) and 73±9% (n=8) relaxation, respectively. The relaxations were attenuated by l‐NOARG, and in LOS strips, the relaxation was abolished by the combination of l‐NOARG and vasoactive intestinal peptide (VIP)‐antiserum (1:25). At resting tension in circular smooth muscle strips from the OB, αLTX induced a scopolamine sensitive contraction in the presence of l‐NOARG.
In circular LOS and OB preparations, αLTX changed the resting membrane potential from −49±2 mV to −59±3 mV (n=4), and −62±2 mV to −71±3 mV (n=4), respectively.
The αLTX‐induced relaxation of LOS and OB muscle was associated with a 138% and 72% increase in cyclic GMP levels, respectively. No changes in cyclic AMP levels were observed.
Ultrastructural analysis of LOS and OB revealed a rich supply of nerve profiles containing small synaptic and large dense core vesicles. αLTX treatment resulted in a loss of both types of vesicle.
These results suggest that αLTX induces relaxation of oesophageal circular smooth muscle associated with NO‐generation and transmitter release from synaptic vesicles. Beside NO, VIP seems to be involved in the relaxant effects of αLTX on the LOS. In addition, αLTX may have contractile effects by release of acetylcholine.

British Journal of Pharmacology (1997) 120, 31–38; doi:10.1038/sj.bjp.0700882
Dose‐ and time‐dependence of l‐NAME neuroprotection in transient focal cerebral ischaemia in rats
Authors: Margaill Isabelle , Allix Monique , Boulu Roger G , Plotkine Michel 
Published: August 2006

In this study the effect of the dose and administration time of NG‐nitro‐l‐arginine methyl ester (l‐NAME), an NO‐synthase inhibitor, in a model of transient focal cerebral ischaemia in rats was investigated.
Two injections of l‐NAME were given, of 1, 3 and 10 mg kg−1, 5 min and 3 h after the onset of ischaemia. None of the doses gave any striatal neuroprotection, but 1 and 3 mg kg−1l‐NAME reduced the infarcted volume in the cortex (by 26%, P<0.01 for 1 mg kg−1 and 21%, P<0.05 for 3 mg kg−1), whereas 10 mg kg−1 had no neuroprotective effect.
Single injections of l‐NAME 1 mg kg−1, given 5 min or 3 h after ischaemia onset, had similar neuroprotective effects on the cortical infarction as did the repeated injections.
l‐NAME 1 mg kg−1 given 3, 6 or 9 h after ischaemia induction reduced the cortical infarct volume by 19% (P<0.01) when given 3 h after ischaemia, by 21% (P<0.01) when given at 6 h, and by 16% (P<0.5) when given at 9 h, but had no neuroprotective activity when given 12 h after ischaemia.
Thus a low dose of l‐NAME is neuroprotective in a model of transient focal ischaemia, with a wide therapeutic window, much larger than that found for MK‐801.

British Journal of Pharmacology (1997) 120, 160–163; doi:10.1038/sj.bjp.0700889
Activation of ecto‐5′‐nucleotidase by protein kinase C and its role in ischaemic tolerance in the canine heart
Authors: Node Koichi , Kitakaze Masafumi , Minamino Tetsuo , Tada Michihiko , Inoue Michitoshi , Hori Masatsugu , Kamada Takenobu 
Published: August 2006

Ischaemic preconditioning (IP) protects the myocardium against irreversible ischaemic injury by activating protein kinase C (PKC). The mechanism by which PKC protects the myocardium is unknown. We have shown that PKC increases the activity of ecto‐5′‐nucleotidase (ecto‐5′‐N) and thereby the production of adenosine in cardiomyocytes which may protect the myocardium against ischaemia‐reperfusion injury in vivo.
The objective of this study was to elucidate the possible role of PKC‐induced activation of ecto‐5′‐N in the cardioprotection associated with IP in the canine heart.
IP increased the activities of both ecto‐5′‐N and PKC, and minimized ischaemic damage (infarct size: 7.5±1.8 vs. 42.3±2.8%, P<0.01 vs. the control group). Treatment with the PKC activator (4β‐phorbol 12‐myristate‐13‐acetate) also reduced infarct size (13.5±2.9%, P<0.01 vs. the control group). 8‐Sulfophenyltheophylline (an antagonist of adenosine receptors) or α,β‐methyleneadenosine 5′‐diphosphate (an inhibitor of ecto‐5′‐N) eliminated the cardioprotective effect of the PKC activator (infarct size: 36.6±3.9 and 34.7±4.2%, respectively), suggesting that PMA limits infarct size by increasing the activity of ecto‐5′‐N and the adenosine level.
The PMA‐induced cardioprotection was blunted by GF109203X (an inhibitor of PKC, infarct size: 36.2±3.1%), but not by pretreatment with dexamethasone (infarct size, 14.2±2.6%).
We conclude that the PMA‐ and IP‐induced cardioprotection is attributable to phosphorylation and activation of ecto‐5′‐N.

British Journal of Pharmacology (1997) 120, 273–281; doi:10.1038/sj.bjp.0700890
Reperfusion injury in the endotoxin‐treated rat heart: reevaluation of the role of nitric oxide
Authors: Yang B C , Chen L Y , Saldeen T G P , Mehta J L 
Published: August 2006

The role of nitric oxide (NO) in ischaemia‐reperfusion injury to the heart continues to be debated.
The role of NO released during endotoxemia on myocardial reperfusion injury was examined in rats given saline or lipopolysaccharide (LPS, 10 mg kg−1).
Aortic rings from LPS‐treated rats showed a markedly decreased contractile response to both noradrenaline (NA) and U46619, and a diminished relaxation response to acetylcholine, thrombin and aggregating platelets. Treatment of rat aortic rings from LPS‐treated rats with the NO synthesis inhibitor Nω‐nitro‐l‐arginine (l‐NOARG) reversed the diminished contractile response to NE and U46619.
Before ischaemia‐reperfusion, baseline force of cardiac contraction (FCC) and coronary perfusion pressure (CPP) were lower and coronary flow was higher in hearts from LPS‐treated rats (all P<0.05 vs. saline‐treated group). Treatment of hearts from LPS‐treated rats with l‐NOARG increased baseline FCC and CPP.
After ischaemia‐reperfusion, hearts from saline‐treated rats showed a 36±5% fall in FCC, a 38±6% rise in CPP and a 38±5% fall in coronary flow, whereas hearts from LPS‐treated rats revealed only a 16±9% fall in FCC, a 10±3% rise in CPP and a 20±4% fall in coronary flow (all P<0.05 vs. changes in saline‐treated group). Fewer hearts from LPS‐treated rats developed reperfusion arrhythmias (6% vs. 60% hearts from saline‐treated rats, P<0.02). Myocardial superoxide dismutase activity was higher in the LPS‐treated group (P<0.05).
NO synthesis, measured as formation of nitrite, was higher (P<0.05) in cardiac and aortic tissues from LPS‐treated rats. Prostacyclin (PGI2) release in coronary effluent was greater in LPS‐treated rat hearts (P<0.05 vs. saline‐treated rats).
Thus LPS‐treated hearts demonstrate a basal decrease in FCC and coronary vascular resistance. These hearts demonstrate a modest protection from reperfusion injury. Induction of NO synthesis, and possibly PGI2 release, may underlie cardioprotection from ischaemia‐reperfusion.

British Journal of Pharmacology (1997) 120, 305–311; doi:10.1038/sj.bjp.0700891
Effects of heptanol on electrical activity in the guinea‐pig vas deferens
Authors: Manchanda R. , Venkateswarlu K. 
Published: August 2006

The effects of the putative intercellular uncoupling agent 1‐heptanol on electrical activity in the guinea‐pig vas deferens were studied by use of intracellular and extracellular recording techniques.
At concentrations of 0.5, 1 and 2 mM, heptanol rapidly, monotonically and reversibly attenuated intracellularly recorded excitatory junction potential (e.j.p.) amplitude without affecting its time course, while spontaneous excitatory junction potentials (s.e.j.ps) were left unaffected.
Heptanol did not affect either the extracellularly recorded evoked excitatory junction current (e.j.c), or the nerve terminal impulse that preceded it. These observations indicate that heptanol does not affect nerve impulse conduction, neurotransmitter release, or the postjunctional receptors involved in the production of the e.j.p.
E.j.ps appear to be suppressed by heptanol due to its intercellular uncoupling effects. Therefore, functional intercellular coupling may be necessary for the generation of the e.j.p. in smooth muscle.
In vivo receptor characterization of neuropeptide Y‐induced effects in consecutive vascular sections of cat skeletal muscle
Authors: Ekelund Ulf , Erlinge David 
Published: August 2006

It has been suggested that the vasoconstrictor response to neuropeptide Y (NPY) is located in the microvessels and that it increases with reduced vessel diameter. The aim of the present study was to analyse quantitatively, on the cat gastrocnemius muscle preparation in vivo, the effects of NPY on total regional vascular resistance (RT) and its distribution to large‐bore arterial resistance vessels (>25 μm; Ra,prcx), small arterioles (<25 μm; Ra,micro) and the veins (Rv). Associated effects on capillary pressure (Pc,v) and fluid exchange were also studied.
Close‐arterially infused NPY (1‐32 μg kg−1 min−1) caused a dose‐dependent, slowly developing vasoconstriction in all three vascular sections, yet with a preferential action in the small arterioles. At 32 μg kg−1 min−1, NPY raised RT by 133 ± 22%, Ra,prox by 94 ± 15%, Ra,micro by 277 ± 104% and Rv by 81 ±11%. However, the veins (ED50 = 3.9 ± 1.2 μg kg−1 min−1) were more sensitive to NPY than both large‐bore arterial vessels (ED50 = 7.7 ± 1.6) and small arterioles (ED50 = 7.0 ± 1.4). NPY decreased Pc,v due to an increase in the pre‐to post‐capillary resistance ratio.
Close‐arterial infusions of Pro34NPY and peptide YY evoked vasoconstrictor responses which did not differ from the response to NPY. In contrast, the Y2‐preferring C‐terminal fragments: Ac‐[Leu28, Leu31]‐NPY(24–36) and NPY(13–36) were without effect in the muscle vascular bed. The selective NPY Y1 receptor antagonist BIBP3226 (100 μg kg−1 min−1, i.a.) abolished the vascular response to NPY.
The present findings indicate that the vasoconstrictor response to NPY in skeletal muscle is preferentially located in the small arterioles and mediated via the Y1 receptor and, further, that Y2 and Y3 receptors do not play a significant role in the vasoconstrictor response to NPY in cat skeletal muscle. BIBP3226 was found to be an effective NPY antagonist in vivo and to lack agonist activity.
Role of potassium channels and nitric oxide in the effects of iloprost and prostaglandin E1 on hypoxic vasoconstriction in the isolated perfused lung of the rat
Authors: Dumas Monique , Dumas Jean‐Paul , Rochette Luc , Advenier Charles , Giudicelli Jean‐François 
Published: August 2006

The aims of this study were to compare in the rat isolated perfused lung preparation, the antagonist effects of iloprost, a stable analogue of prostacyclin, and prostaglandin E1 (PGE1) on the hypoxic pulmonary pressure response, and to investigate the possible involvement of KATP and KCa channels and of EDRF (NO) in these effects. In addition, iloprost and PGE1 effects were compared to those of adenosine and forskolin.
Isolated lungs from male Wistar rats (260–320 g) were ventilated with 21% O2 + 5% CO2 + 74% N2 (normoxia) or 5% CO2 + 95% N2 (hypoxia) and perfused with a salt solution supplemented with ficoll. Glibenclamide (1 μm), charybdotoxin (0.1 μm), NG‐nitro‐L‐arginine methyl ester (l‐NAME, 100 μm) were used to block KATP, KCa channels and NO synthesis, respectively.
Iloprost, PGE1, adenosine and forskolin caused relaxation during the hypoxic pressure response. The order of potency was: iloprost > PGE1 = forskolin > adenosine. EC50 values were 1.91 ± 0.52 10−9 M, 3.31 ± 0.58 10−7 M, 3.24 ± 0.78 10−7 M and 7.70 ± 1.68 10−5 M, respectively. Glibenclamide, charybdotoxin and L‐NAME inhibited partially the relaxant effects of iloprost and forskolin but not those of PGE1.
It is concluded that in the rat isolated lung preparation, iloprost and forskolin but not PGE1 dilate pulmonary vessels partly through KATP channels, KCa channels and nitric oxide release. Furthermore our results suggest that the role of cyclic AMP in these effects is not unequivocal.
Activation by high potassium of a novel voltage‐operated Ca2+ channel in rat spleen
Authors: Ko Feng‐Nien , Huang Shu‐Yi , Teng Che‐Ming 
Published: August 2006

High potassium produced a concentration‐dependent contraction in rat isolated spleen.
The high potassium‐induced contraction of rat spleen was abolished in Ca2+‐free Krebs solution containing 1 mM EGTA, and the subsequent addition of 3 mM Ca2+ restored the high potassium‐induced contraction to the control level.
Nifedipine, verapamil, diltiazem, Cd2+, Ni2+, Co2+, R‐(+)‐Bay K 8644 and pimozide inhibited and relaxed high potassium‐induced contraction of rat spleen with IC50 and EC50 values much higher than those values in rat aorta.
In addition, high potassium‐stimulated contraction of rat spleen was insensitive to ω‐conotoxin GVIA, ω‐conotoxin MVIIC and ω‐agatoxin IVA.
The high potassium‐induced contraction of rat spleen was also unaffected by tetrodotoxin (TTX), prazosin, chloroethylclonidine (CEC), yohimbine, propranolol, atropine, diphenhydramine, cimetidine, ketanserin, 3‐tropanyl‐indole‐3‐carboxylate, saralasin, indomethacin, nordihydroguaiaretic acid, GR32191B, domperidone, naloxone, chlorpromazine, suramin, (±)‐2‐amino‐5‐phosphonopentanoic acid, 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX), L‐659,877, L‐703,606, lorglumide, PD 135,158 N‐methyl‐D‐glucamine, benextramine, amiloride, dantrolene, TMB‐8, econazole, staurosporine and neomycin.
Forskolin and sodium nitroprusside relaxed high potassium‐induced contraction of rat spleen with EC50 values of 0.55 ± 0.04 and 20.0 ± 2.7 μm, respectively.
It is concluded that high potassium may activate a novel, pharmacologically uncharacterized voltage‐operated Ca2+ channel in rat spleen.
Inhibition by rapamycin of ornithine decarboxylase and epithelial cell proliferation in intestinal IEC‐6 cells in culture
Authors: Seidel E.R. , Ragan V.L. 
Published: August 2006

Induction of the enzyme ornithine decarboxylase (ODC) appears to be controlled primarily at the level of ODC mRNA translation. The immunosuppressant drug, rapamycin, blocked the induction of ODC in response to serum by roughly 50% but was without effect on transport of putrescine into the intracellular space. The effect on ODC was specific for the intracellular signalling pathway leading to activation of p70S6k, as the immunosuppressant FK 506 was without effect on ODC activity.
Exposure of IEC‐6 duodenal epithelial cells to rapamycin inhibited cellular proliferation. The effect of rapamycin was cytostatic in that removal of the immunosuppressant from the medium resulted in renewed cell division. Conversely, addition of exogenous putrescine, the product of the ODC catalysed reaction, was unable to reverse the cytostatic effects of rapamycin.
At a concentration of 10 nM, rapamycin inhibited the induction of ODC by 50%, a level of inhibition which could not be enhanced by exposure cells to 1000 nM rapamycin. This observation suggests that other intracellular signalling pathways, in addition to the p70S6k cascade, might be involved in regulation of translation of ODC mRNA or that rapamycin does not completely inhibit p70S6k.
Anti‐insulin‐like growth factor‐I activity of a novel polysulphonated distamycin A derivative in human lung cancer cell lines
Authors: De Cupis Alessandra , Ciomei Marina , Pirani Paolo , Ferrera Alessandra , Ardizzoni Andrea , Favoni Roberto Enrico 
Published: August 2006

The purpose of this study was to investigate the antiproliferative effect and the modulation of the mitogenic insulin‐like growth factor‐I (IGF‐I) system by FCE 26644 and FCE 27784, two polyanionic sulphonated distamycin A derivative compounds, on two human non‐small cell lung cancer (N‐SCLC) cell lines.
For cell growth studies the colorimetric MTT and the thymidine incorporation assays were performed; the presence of IGF‐I and IGF‐binding proteins in conditioned media was revealed by radioimmunoassay and Western ligand blot, respectively. Variations at the IGF‐I‐receptor level were tested by binding studies on cell monolayers.
A significant concentration‐and time‐dependent cytostatic activity of FCE 26644 (IC50∼200 μg ml−1 at 72 h) compared to its analogue FCE 27784 (IC50>8OO μg ml−1) was observed in both cell lines studied. The IGF‐I‐stimulated proliferation of the IGF‐I‐responsive A549 cell line was abolished by 24 h of FCE 26644 treatment whereas FCE 27784 was inactive. FCE 26644 increased (4 to 6 fold) the secretion of IGF‐I‐like material and reduced the IGF‐I binding (IC50>100 μg ml−1) in both A549 and Ca‐Lu‐1 cell lines. FCE 26644 (100 μg ml−1) did not affect the KD (∼0.5 nM) but reduced the Bmax and the number of receptor sites (50%).
Our findings demonstrate that the ability to down‐regulate the cell proliferation of N‐SCLC cell lines, shown by FCE 26644, depends at least partially, on interference with the ‘IGF‐I mitogenic system’.
Aminoguanidine‐effects on endoneurial vasoactive nitric oxide and on motor nerve conduction velocity in control and streptozotocin‐diabetic rats
Authors: Dewhurst M. , Omawari N. , Tomlinson D.R. 
Published: August 2006

The effects of aminoguanidine (AG) treatment on reductions in motor nerve conduction velocity (MNCV) and sciatic nerve blood flow, indexed by laser Doppler flux (LDF), were investigated in rats with experimental diabetes (streptozotocin‐induced; 8–10 weeks duration). The contribution of endoneurial vasoactive nitric oxide to the LDF of these animals was also investigated by the direct micro‐injection of NG‐nitro‐L‐arginine methyl ester (l‐NAME; 1 nmol in 1 μ1), followed by L‐arginine (100 nmol in 1 μI), into the sciatic nerve endoneurium.
The MNCV (m s−1, mean ± 1 s.d.) of diabetic rats (38.2 ± 1.5) was lower (P<0.01) than that of age‐matched controls (47.2 ± 4.2). AG treatment (50 mg kg−1 day−1, i.p.) attenuated the diabetes‐induced deficits in MNCV (43.4±5.9; P<0.01), but had no effect in controls (48.8±3.8) or, if administered via drinking water (1 g 1−1), diabetics (37.4 ± 4.1).
L‐NAME markedly reduced the resting LDF (arbitrary units; mean ± s.e.mean) of controls (209 ± 13 to 120± 18; P<0.005), an effect reversed by subsequent L‐arginine (to 206±27). In diabetic rats the LDF reduction following L‐NAME was much smaller (111 ±11 to 84 ± 6; P<0.05), but the change with L‐arginine was significantly increased (to 145±12; P<0.001).
AG treatment increased the resting LDF of control (265 ± 34) and diabetic rats (133 ± 14 for daily injection and 119±13 for drinking water). The responses to L‐NAME and L‐arginine were not changed markedly by AG treatment. However, L‐arginine appeared to be less effective.
In conclusion, these data suggest that AG treatment may affect nitric oxide production in the vasa nervorum of peripheral nerves. However, the effects of AG‐treatment are not consistent with the prevention of a diabetes‐associated reduction in endoneurial nitric oxide production. The mechanisms by which AG attenuates nerve conduction slowing in streptozotocin‐diabetic rats therefore remain unclear.