bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of PAF on excitatory neuro‐effector transmission in dog airways
Authors: Tashiro Kazuhiro , Xie Zhuoqiu , Ito Yushi 
Published: July 2012

Effects of PAF on excitatory neuro‐effector transmission in smooth muscle cells of mucosa‐free trachea and epithelium‐intact bronchiole of the dog were investigated, by isometric tension recording, microelectrode and double sucrose‐gap methods.
PAF (10−11 − 10−7 m) dose‐dependently enhanced the amplitude of contraction evoked by repetitive field stimulations (10 stimuli at 20 Hz) in both tracheal and bronchiolar tissues. At higher concentrations PAF (> 10−8 m) increased the amplitude of contraction to a greater extent in the bronchiole than in the trachea.
In both muscle tissues, in parallel to the amplitude of contraction, PAF markedly enhanced the amplitude of excitatory junction potentials (e.j.ps) evoked by a single field stimulation in a dose‐dependent manner, with no change in the resting membrane potential or input membrane resistance of the smooth muscle cells. PAF (5 × 10−7 m) enhanced the amplitude of e.j.p. to a greater extent in the bronchiole than in the trachealis. In contrast, lyso‐PAF (10−10 − 10−7 m) showed no effect on e.j.p. amplitude in bronchiolar tissues. At a high concentration (10−7 m) lyso‐PAF slightly enhanced the e.j.p. amplitude in tracheal tissue, however the lyso‐PAF induced stimulation of e.j.p. amplitude in the trachea was small compared to that of PAF.
PAF (10−7 m) had no effect on the membrane depolarization induced by acetylcholine (ACh, 10−9 − 10−5 m) and carbachol (10−9 − 10−5 m) in tracheal smooth muscle cells.
The PAF‐antagonists CV3988 (5 × 10−7 m) or WEB2086 (5 × 10−7 m) significantly enhanced the e.j.p. amplitude themselves, PAF (5 × 10−8 m) further enhanced the e.j.p. amplitude in the presence of WEB2086 (5 × 10−7 m) but not CV3988 (5 × 10−7 m). In contrast, the new PAF‐antagonist, E 6123 (5 × 10−8 m), did not affect the e.j.p. amplitude itself, and completely inhibited the increase in e.j.p. amplitude caused by 5 × 10−8 m PAF. On the other hand, in the presence of the H1‐antagonist, mepyramine, PAF (5 × 10−8 m) further enhanced the e.j.p. amplitude.
The leukotriene synthesis inhibitor AA‐861 (10−6 m) or leukotriene antagonist ONO1078 (10−7 m) inhibited the increase in e.j.p. amplitude caused by 5 × 10−8 m PAF, respectively.
In the presence of AA‐861 (10−6 m), leukotriene B4 (LTB4, 10−8 m) or LTD4 (10−8 m) slightly, and LTC4 (10−8 m) markedly enhanced the e.j.p. amplitude. In contrast, LTE4 (10−8 m) significantly suppressed the e.j.p. amplitude.
PAF (5 × 10−8 m) attenuated the depression phenomena of e.j.ps observed during double stimulus experiments at different time intervals (5–10 s), but had no effect on the summation of e.j.ps during repetitive field stimulation at a high frequency (20 Hz) in the trachealis.
These results indicate that PAF potentiates excitatory neuro‐effector transmission mainly through stimulating the release of lipoxygenase products, mainly LTC4 in the dog airway smooth muscle tissues.
Role of the l‐arginine‐NO pathway and of cyclic GMP in electrical field‐induced noradrenaline release and vasoconstriction in the rat tail artery
Authors: Bucher Bernard , Ouedraogo Sylvin , Tschöpl Martin , Paya Dominique , Stoclet Jean‐Claude 
Published: July 2012

The possible roles of the l‐arginine‐NO pathway and of guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) in regulating the prejunctional release of noradrenaline and neurogenic vasoconstriction were investigated in the perfused rat tail artery.
In the presence of Nω‐nitro‐l‐arginine methyl ester (l‐NAME; 30 μm), an inhibitor of NO formation, the vasoconstrictor responses to perivascular nerve stimulation (24 pulses at 0.4 Hz, 0.3 ms, 200 mA) and to exogenous noradrenaline (1 μm) were significantly enhanced, whereas the stimulation‐evoked tritium overflow from [3H]‐noradrenaline preloaded arteries was not modified. The vasoconstriction enhancing effect of l‐NAME was prevented by l‐arginine (1 mm) but not d‐arginine (1 mm) and was abolished by removal of the endothelium.
The NO donor, 3‐morpholinosydnonimine‐N‐ethylcarbamide (SIN‐1; 0.1–30 μm), and the cyclic GMP phosphodiesterase inhibitor, zaprinast (0.1–30 μm) both induced a concentration‐dependent inhibition of the electrical field stimulation‐induced vasoconstriction, while atrial natriuretic peptide (ANP; 100 nm) produced only a slight decrease of the vasoconstrictor response. Methylene blue (3μm), a known inhibitor of soluble guanylate cyclase increased the electrical field stimulation‐induced vasoconstriction. SIN‐1 and methylene blue when administered simultaneously, antagonized each others effect. None of the compounds tested (SIN‐1, zaprinast, ANP or methylene blue) had any significant effect on the stimulation‐evoked [3H]‐noradrenaline overflow.
8‐Bromo‐cyclic GMP, a potent activator of cyclic GMP‐dependent protein kinase, markedly and concentration‐dependently (3–300 μm) increased [3H]‐noradrenaline overflow but decreased field stimulation‐induced vasoconstriction. Dibutyryl‐cyclic GMP (100 μm), a weak activator of cyclic GMP‐dependent protein kinase, affected neither the pre‐ nor the postjunctional response to electrical field stimulation.
These data show that an NO‐like substance of endothelial origin, derived from l‐arginine, attenuates vasoconstriction in the rat tail artery, whether neurally‐induced or evoked by exogenous noradrenaline. Since noradrenaline release was unaltered by compounds modifying NO production, this NO‐like compound acted through a postjunctional mechanism. The lack of prejunctional effects of both soluble and membrane‐associated guanylate cyclase activators, despite a large effect of 8‐bromo‐cyclic GMP, suggests that endogenous cyclic GMP production, if present in sympathetic nerves, may not be involved in the regulation of noradrenaline release in the rat tail artery.
BK1 and BK2 bradykinin receptors in the rat duodenum smooth muscle
Authors: Feres Teresa , Paiva Antonio C.M. , Paiva Therezinha B. 
Published: July 2012

The dual action of bradykinin (relaxation and contraction) on the rat duodenum was investigated by studying its effect on adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) levels in cultured duodenal smooth muscle cells, and the effects of apamin on the isolated muscle responses to agonists and antagonists of BK1 and BK2 receptors.
No change was observed in the cyclic AMP content of cultured cells incubated with up to 100 nm bradykinin.
Apamin (100–500 nm) inhibited the relaxant component and enhanced the contractile component of the responses to bradykinin and to the BK2‐specific analogue [Thi5,8,d‐Phe7]‐bradykinin.
Apamin (100–500 nm) did not affect the contractile response of stretched duodenum preparations to the BK1‐specific agonist des‐Arg9‐bradykinin.
The BK2 antagonist, [d‐Arg0Hyp3Thi5,8,d‐Phe7]‐bradykinin, at a concentration which completely inhibited the relaxant response to bradykinin and to [Thi5,8,d‐Phe7]‐bradykinin, also prevented the contraction in response to either agonist in the presence of apamin.
Our results demonstrate two populations of bradykinin receptors in rat duodenum: a BK2 subtype responsible for the biphasic response of the non‐stretched duodenum, and a BK1 subtype responsible for the contractile effect on the stretched tissue.
Central administration of 5‐HT activates 5‐HT1A receptors to cause sympathoexcitation and 5‐HT2/5‐HT1C receptors to release vasopressin in anaesthetized rats
Authors: Anderson Ian K. , Martin Graeme R. , Ramage Andrew G. 
Published: July 2012

The effects of intracerebroventricular injections to the right lateral ventricle (i.c.v.) of 5‐hydroxytryptamine (5‐HT, 40 and 120 nmol kg−1), N,N‐di‐n‐propyl‐5‐carboxamidotryptamine (DP‐5‐CT; 3 nmol kg−1), 5‐carboxamidotryptamine (5‐CT; 3 nmol kg−1), 8‐hydroxy‐2‐(di‐N‐propylamino) tetralin (8‐OH‐DPAT; 3, 40 and 120 nmol kg−1) and 1‐(2,5‐di‐methoxy‐4‐iodophenyl)‐2‐aminopropane (DOI; 40 and 120 nmol kg−1) on renal sym pathetic nerve activity, blood pressure, heart rate and phrenic nerve activity were investigated in normotensive rats anaesthetized with α‐chloralose.
5‐HT caused a long lasting pressor response which was associated with an initial bradycardia and renal sympathoinhibition followed by a tachycardia and renal sympathoexcitation. Pretreatment with the 5‐HT2/5‐HT1C receptor antagonists, cinanserin (300 nmol kg−1, i.c.v.) or LY 53857 (300 nmol kg−1, i.c.v.) reversed the initial bradycardia and sympathoinhibition to tachycardia and sympathoexcitation. Combined pretreatment with LY 53857 (300 nmol kg−1, i.c.v.) and the 5‐HT1A antagonist, spiroxatrine (300 nmol kg−1, i.c.v.), blocked the effects of 5‐HT on all the above variables.
Pretreatment with the vasopressin V1‐receptor antagonist, β‐mercapto‐β,β‐cyclopentamethylenepropionyl1, O‐Me‐Tyr2, Arg8‐vasopressin [(d(CH2)5Tyr(Me)AVP, 10 μg kg−1, i.v.] did not affect the magnitude but reduced the duration of the pressor response produced by i.c.v. 5‐HT and reversed the initial bradycardia and renal sympathoinhibition to tachycardia and sympathoexcitation.
1‐(2,5‐Di‐methoxy‐4‐iodophenyl)‐2‐aminopropane (DOI) caused a pressor effect which was associated with a bradycardia and sympathoinhibition. These effects were blocked by pretreatment with BW501C67 (0.1 mg kg−1, i.v.), a peripherally acting 5‐HT2/5‐HT1C receptor antagonist. However, BW501C67 (0.1 mg kg−1, i.v.) failed to block the effects of i.c.v. 5‐HT.
DP‐5‐CT, 5‐CT and 8‐OH‐DPAT (3 nmol kg−1, i.c.v.) caused sympathoexcitation, tachycardia and a rise in blood pressure. Pretreatment with methiothepin (1 mg kg−1, i.v.) or spiroxatrine (300 nmol kg−1, i.c.v.) attenuated the response to i.c.v. DP‐5‐CT.
It is concluded that i.c.v. administration of 5‐HT activates 5‐HT1A receptors to cause sympathoexcitation and 5‐HT2 or 5‐HT1C receptors to cause the release of vasopressin.
Stereospecific antiarrhythmic effects of naloxone against myocardial ischaemia and reperfusion in the dog
Authors: Lee Andrew Ying‐Siu 
Published: July 2012

The effects of both the (−)‐ and (+)‐stereoisomers of naloxone in anaesthetized dogs with arrhythmias induced by acute coronary artery occlusion followed by reperfusion were investigated.
Following coronary artery occlusion and reperfusion, all dogs in the control group developed ischaemia‐ and reperfusion‐induced cardiac arrhythmias, bradycardia and hypotension.
The opiate antagonist (−)‐naloxone prevented the arrhythmias, bradycardia and hypotension due to myocardial ischaemia and reperfusion.
The (+)‐stereoisomer of naloxone, which is inactive as an opiate antagonist, was without beneficial effects.
These results indicate a possible involvement of endogenous opioid peptides in the cardiac effects due to myocardial ischaemia and reperfusion, mediated by opiate receptors through opiate antagonism.
ATP activates P2x‐contracting and P2y‐relaxing purinoceptors in the smooth muscle of mouse vas deferens
Authors: Boland Benoit , Himpens Bernard , Vincent M. Françoise , Gillis Jean‐Marie , Casteels Rik 
Published: July 2012

The mechanism for the low potency of exogenous ATP in producing contraction at the P2x‐purinoceptors in the smooth muscle of the mouse vas deferens (VD) was examined.
The measure of the breakdown of ATP in contact with the VD showed that its degradation was limited and did not account for its weak contractile effect.
Externally applied, ATP induced a small and transient contraction but a marked and prolonged increase of the cytosolic Ca2+ concentration ([Ca2+]i), which suggests an efficient binding to the P 2x‐purinoceptors. Such a calcium‐force dissociation was not observed with β,γ‐methylene ATP (β,γ‐Me‐ATP), a structural ATP analogue.
The force response of precontracted VD to ATP was biphasic, consisting of a small initial contraction followed by a sustained marked relaxation. In contrast, β,γ‐Me‐ATP elicited a pronounced contraction without ensuing relaxation.
ATP was more potent than adenosine in producing relaxation, and the relaxation was not antagonized by 8‐phenyltheophylline, suggesting the activation of P2‐purinoceptors.
For this relaxation, the rank order of potency was 2‐methyl‐thio‐ATP (2‐MeSATP) > ATP>β,γ‐Me‐ATP, which is characteristic for the P2y‐purinoceptors.
Reactive Blue 2, a P2y‐purinoceptor antagonist, was found to reduce the relaxation mediated by ATP.
These results indicate that ATP acts in VD not only on contracting but also on relaxing P2‐purinoceptors, eliciting thereby overlapping opposite effects. In VD, the classical low potency of ATP for contraction is thus not explained by its low bioavailability or its low binding, but rather by its low specificity for the contracting P2x‐purinoceptors, leading to the activation of the relaxing P2y‐purinoceptors.
Protective effects of inhibitors of nitric oxide synthase in immune complex‐induced vasculitis
Authors: Mulligan M.S. , Moncada S. , Ward P.A. 
Published: July 2012

The ability of analogues of l‐arginine (N‐iminoethyl‐l‐ornithine (l‐NIO), NG‐monomethyl‐l‐arginine (l‐NMMA), NG‐nitro‐l‐arginine methyl ester (l‐NAME) and NG‐nitro‐l‐arginine (l‐NNA)) to protect against inflammatory injury induced by activated neutrophils was investigated in rats following intradermal or intrapulmonary deposition of immune complexes.
The descending order of potency for protective effects of these analogues was: l‐NIO > l‐NMMA > l‐NNA = l‐NAME. The approximate IC50 value for l‐NIO in the dermal vasculitis model was 65 μm. For all other compounds, the IC50 values were > 5 mm.
The protective effect of l‐NIO in the skin was reversed in a dose‐dependent manner by the presence of l‐arginine, but not by d‐arginine. l‐Arginine also reversed the protective effects of l‐NIO in immune complex‐induced lung injury.
The protective effects of l‐NIO were not associated with reductions in neutrophil accumulation, as measured by extraction from tissues of myeloperoxidase.
These data demonstrate that l‐NIO has the most potent protective effects against immune complex‐induced vascular injury induced by activated macrophages. Furthermore, they indicate that this injury is dependent upon the generation of nitric oxide.
Palmitoyl‐dl‐carnitine has calcium‐dependent effects on cultured neurones from rat dorsal root ganglia
Authors: Stapleton Simon R. , Currie Kevin P.M. , Scott Roderick H. , Bell B. Anthony 
Published: July 2012

The effects of palmitoyl‐dl‐carnitine (0.01 to 1 mm) on whole cell voltage‐activated calcium channel currents carried by calcium or barium and Ca2+‐activated chloride currents were studied in cultured neurones from rat dorsal root ganglia.
Palmitoyl‐dl‐carnitine applied to the extracellular environment or intracellularly via the patch solution reduced Ca2+ currents activated over a wide voltage range from a holding potential of −90 mV. Inhibition of high voltage activated Ca2+ channel currents was dependent on intracellular Ca2+ buffering and was reduced by increasing the EGTA concentration from 2 to 10 mm in the patch solution. Barium currents were significantly less sensitive to palmitoyl‐dl‐carnitine than Ca2+ currents.
The amplitude of Ca2+‐activated Cl− tail currents was reduced by palmitoyl‐dl‐carnitine. However, the duration of these Cl− currents was greatly prolonged by palmitoyl‐dl‐carnitine, suggesting slower removal of free Ca2+ from the cytoplasm following Ca2+ entry through voltage‐activated channels.
Palmitoyl‐dl‐carnitine evoked Ca2+‐dependent inward currents which could be promoted by activation of the residual voltage‐activated Ca2+ currents and attenuated by intracellular application of EGTA.
We conclude that palmitoyl‐dl‐carnitine reduced the efficiency of intracellular Ca2+ handling in cultured dorsal root ganglion neurones and resulted in enhancement of Ca2+‐dependent events including inactivation of voltage‐activated Ca2+ currents. The activation of inward currents by palmitoyl‐dl‐carnitine may involve Ca2+‐induced Ca2+ release from intracellular stores, or direct interaction of palmitoyl‐dl‐carnitine with Ca2+ stores.
Inhibition of neuropeptide Y‐induced potentiation of noradrenaline‐induced vasoconstriction by PP56 (d‐myo‐inositol 1,2,6‐tris‐phosphate)
Authors: Adamsson M. , Fallgren B. , Edvinsson L. 
Published: July 2012

Although neuropeptide Y (NPY) is a potent vasoconstrictor in many vascular beds, nanomolar concentrations of this peptide potentiate the noradrenaline‐induced contractions in rabbit gastroepiploic and femoral arteries, and guinea‐pig mesenteric and uterine arteries.
The potentiating effect of NPY on noradrenaline‐induced contraction was present in endothelium‐denuded femoral arteries.
The potentiating effect of NPY on noradrenaline‐induced contraction was antagonized by PP56 (d‐myo‐inositol 1,2,6‐trisphosphate) in low concentrations (down to 0.1 nm). This antagonistic effect was observed in all four types of vessels studied. Contractions induced by noradrenaline, histamine, endothelin‐1 and potassium were not altered by PP56 in concentrations upto 1 μm in femoral artery of rabbit.
We provide evidence that a non‐peptide (PP56) can selectively antagonize NPY‐induced effects in rabbit and guinea‐pig peripheral arteries without affecting the vasoconstrictor response to noradrenaline.
Mechanisms contributing to the regional haemodynamic effects of neurotensin in conscious, unrestrained Long Evans rats
Authors: Bachelard Hélène , Gardiner Sheila M. , Kemp Philip A. , Bennett Terence 
Published: July 2012

The regional haemodynamic effects of i.v. bolus doses of neurotensin (10–1000 ng) were assessed in conscious, unrestrained Long Evans rats chronically instrumented with miniaturized, pulsed Doppler probes.
Neurotensin caused increases in blood pressure, together with dose‐related tachycardias and constrictions in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia elicited by the 1000 ng dose of neurotensin was preceded by a transient bradycardia.
In the presence of phentolamine, the pressor effect of neurotensin (1000 ng) was converted into a hypotensive effect, accompanied by reduced tachycardic and constrictor responses in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia was not preceded by a bradycardia.
In the presence of phentolamine and propranolol, the pressor and bradycardic responses to neurotensin were unaffected, whereas the tachycardia was abolished. The renal vasconstrictor effect was smaller, while the constrictions in the superior mesenteric and hindquarters vasculars beds were not different from those in untreated rats.
In rats neonatally treated with capsaicin (50 mg kg−1, s.c.), the pressor effects elicited by neurotensin (300 and 1000 ng) were reduced as were the constrictor responses in the renal (at the dose of 300 ng), superior mesenteric (at the dose of 300 ng) and hindquarters (at both doses) vascular beds. The bradycardia elicited by neurotensin (1000 ng) was absent, whereas the tachycardia was potentiated.
The results indicate that in conscious, intact rats neurotensin appears to exert cardiovascular influences through activation of sympathoadrenal mechanisms and also through non‐adrenergic effects on the heart, renal, superior mesenteric and hindquarters vascular beds. The latter effects appear to involve capsaicin‐sensitive nerves.
Mechanisms of coronary vasodilatation produced by ATP in guinea‐pig isolated perfused heart
Authors: Brown Ina P. , Thompson Carl I. , Belloni Francis L. 
Published: July 2012

Isolated hearts of guinea‐pigs were perfused in vitro with a physiological salt solution via a retrograde aortic cannulation (Langendorff preparation) at constant perfusion pressure. Bolus intra‐arterial injections of various vasodilator drugs were made and the coronary flow responses were measured with an electromagnetic flow probe placed in the arterial inflow circuit. Inhibitory drugs were infused intra‐arterially.
Nitro‐l‐arginine (NLA; 500 μm), an NO synthesis inhibitor, decreased coronary baseline flow by 16 ± 0.8%, converted acetylcholine‐induced coronary vasodilatation to vasoconstriction and had no effect on coronary flow responses to adenosine or papaverine. Sodium nitroprusside‐induced responses were enhanced during NLA infusion by 46 ± 11%.
Adenosine 5′‐triphosphate (ATP) increased coronary flow but coronary flow responses to ATP were not altered by infusion of NLA.
ATP‐induced coronary dilatation was not significantly attenuated by infusion of the adenosine receptor antagonist XAC, (xanthine amine congener; 2 μm), whereas XAC decreased coronary flow responses to adenosine by 75% ± 5%.
ATP‐induced coronary flow responses were reduced by only 31 ± 4% during indomethacin infusion (2.8 μm) whereas indomethacin completely eliminated the initial vasoconstriction phase and greatly attenuated the peak flow and duration of the later vasodilatation phase seen in response to arachidonic acid (0.75 nmol). Indomethacin had no effect on vasodilatations produced by adenosine or prostaglandin I2.
These results indicate that ATP‐induced coronary dilatation in the isolated, perfused heart of the guinea‐pig is not dependent upon NO production or upon degradation of ATP to adenosine. The coronary dilator action of ATP may be partially dependent (∼30%) upon the production of vasodilator prostaglandins.
In vitro characterization of prostanoid FP‐, DP‐, IP‐ and TP‐receptors on the non‐pregnant human myometrium
Authors: Senior J. , Sangha R. , Baxter G.S. , Marshall K. , Clayton J.K. 
Published: July 2012

Prostaglandin F (PGF), PGD, PGI and thromboxane A2 (TXA2) receptors have been pharmacologically characterized on the non‐pregnant human myometrium in vitro in accordance with the receptor classification proposed by Coleman et al. (1984). The tools for the classification include both natural prostanoids, synthetic, selective analogues and antagonists where available.
The potent excitatory actions of the natural FP‐receptor prostanoid, PGF2α, and the synthetic analogue, fluprostenol, indicate the presence of FP‐receptors mediating contraction on the human myometrium.
PGD2 produced a biphasic response consisting of excitation followed by relaxation of spontaneous activity of the myometrium. The selective DP‐receptor agonists, BW245C, produced purely inhibitory responses illustrating the presence of inhibitory DP‐receptors in this tissue. The inhibitory responses of both PGD2 and BW245C were antagonized by the competitive DP‐receptor antagonist, BWA 868C, providing conclusive evidence for the existence of DP‐receptors.
PGI2 produced a biphasic response similar to PGD2. Iloprost, the EP1/IP‐receptor agonist also produced a biphasic response, whilst the IP‐receptor selective agonist, cicaprost, caused inhibition only, suggesting that inhibitory IP‐receptors exist in the non‐pregnant human myometrium.
The TXA2‐mimetic, U46619, produced marked stimulation of the non‐pregnant human myometrium and was approximately equipotent to PGF2α and fluprostenol in this effect. The actions of U46619 were competitively antagonized by the TP‐receptor antagonist GR32191 showing that excitatory TP‐receptors exist in this tissue.6 All prostanoids tested, both natural and synthetic, had activity on the non‐pregnant human myometrium in vitro, supporting the existence of a heterogeneous population of prostanoid receptors in this tissue. If the results from the present study are combined with those previously reported for EP‐receptor agonists (Senior et al., 1991), it may be concluded that excitation may occur through FP‐, TP‐, EP3‐ and few EP1‐receptors, whereas inhibition may occur through DP‐, IP‐ and EP2‐receptors.