bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low intimacy as a mediator between depression and clinic couple relationship satisfaction
Authors: FINKBEINER NICOLE M. , EPSTEIN NORMAN B. , FALCONIER MARIANA K. 
Published: July 2012

AbstractThis study examined low intimacy as a mediator between partners' depression symptoms and low relationship satisfaction in a sample of 82 heterosexual couples who sought therapy at an outpatient clinic. Both the amount of intimate behavior that partners enact and the level of pleasure they experience from each other's intimate acts were assessed. Using an actor–partner interdependence model approach, path model analysis simultaneously included both partners' scores on measures of depression, intimate behavior, pleasure from partner's intimate behavior, and relationship satisfaction. Overall, female depression symptoms had a greater impact than male depression symptoms on the couple relationship. Male depression had little effect on intimacy, whereas the female partner's depression affected her pleasure from the male's intimate behavior and both partners' enactment of intimate behavior. The results indicate the importance of examining reciprocal influences between partners' functioning to understand and treat intimacy problems.
Central neuropeptide Y and the sigma ligand, JO 1784, reverse corticotropin‐releasing factor‐induced inhibition of gastric acid secretion in rats
Authors: Gué M. , Yoneda M. , Mönnikes H. , Junien J.‐L. , Taché Y. 
Published: July 2012

The central interactions between the sigma ligand, JO 1784, [(+)‐N‐cylcopropylmethyl‐N‐methyl‐1,4‐diphenyl‐1‐ethylbut‐3‐en‐1‐ylamine hydrochloride], or neuropeptide Y (NPY) and corticotropin‐releasing factor (CRF)‐induced inhibition of gastric acid secretion were investigated in rats anaesthetized with urethane. Drugs were injected intracisternally (i.c.) or into specific hypothalamic nuclei. Gastric acid secretion was measured by the flushed technique under basal and pentagastrin (10 μg kg−1 h−1, i.v.) stimulated conditions.
Intracisternal injection of CRF (10 μg), bombesin (0.1 μg) and human recombinant interleukin‐1β (hIL‐1β, 0.1 μg) inhibited gastric acid response to pentagastrin by 72%, 56% and 62%, respectively. NPY (0.5 μg) or JO 1784 (0.5 μg) injected i.c. did not alter acid secretion but completely prevented the inhibitory effect of CRF. The antagonistic effect of NPY and JO 1784 against CRF was dose‐related (0.01–0.5 μg) and peptide‐specific since NPY and JO 1784 did not alter the antisecretory action of bombesin or hIL‐1β.
The putative sigma receptor antagonist, BMY 14802, (1 mg kg−1, s.c.) did not influence pentagastrin‐stimulated acid secretion nor CRF‐induced inhibition of gastric acid secretion; however, BMY 14802 administered s.c. 20 min before JO 1784 or NPY, abolished the antagonistic effect of both JO 1784 and NPY.
CRF (3 μg) microinjected into the hypothalamic paraventricular nucleus (PVN) and the lateral hypothalamus (LH) inhibited pentagastrin‐stimulated gastric acid secretion by 61% and 51%; NPY (0.03 μg) or JO 1784 (0.03 μg) microinjected into the PVN had no effect by themselves but blocked CRF antisecretory action. Microinjection into the LH had no effect.
In conclusion, NPY and JO 1784 (a sigma ligand) interacts with CRF in the PVN to block CRF‐induced inhibition of pentagastrin‐stimulated gastric acid secretion. The central action of JO 1784 and NPY is specific to CRF and may involve sigma binding sites.
Modification by hypoxia, hyperkalaemia and acidosis of the cardiac electrophysiological effects of a range of antiarrhythmic drugs
Authors: Pacini D.J. , Boachie‐Ansah G. , Kane K.A. 
Published: July 2012

The electrophysiological effects of a series of drugs with Class I antiarrhythmic activity were examined in sheep Purkinje fibres, superfused in vitro with either a normal or hypoxic, hyperkalaemic and acidotic physiological salt solution (PSS).
In normal sheep Purkinje fibres, lignocaine, disopyramide, nicainoprol and propranolol all significantly reduced action potential height and the maximum rate of depolarization of phase zero (MRD) and abbreviated the action potential, without modifying resting membrane potential (RMP).
Verapamil at the highest concentration studied, 8 μm, significantly reduced MRD with an associated slight membrane depolarization and abbreviated action potential duration measured at 50% repolarization (APD50).
Superfusion of sheep Purkinje fibres with a hypoxic, hyperkalaemic and acidotic PSS resulted in marked reductions in resting membrane potential, upstroke and duration of the action potential.
In the presence of modified PSS, lignocaine, propranolol and verapamil all reduced MRD to a greater extent than in normal PSS. The effects of nicainoprol on MRD were not affected whereas those of disopyramide were significantly attenuated.
Under simulated ischaemic conditions, lignocaine, propranolol and nicainoprol did not produce a concentration‐dependent reduction in action potential duration whereas disopyramide and verapamil, respectively, prolonged and abbreviated both APD50 and APD90.
The Na+ channel blocking actions of the different subtypes of Class I antiarrhythmic agents studied, as well as their effects on action potential duration, were modified differently by simulated ischaemia.
Human α‐calcitonin gene‐related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide
Authors: Gray David W. , Marshall Ian 
Published: July 2012

The signal transduction pathway for vasorelaxation induced by human α‐calcitonin gene‐related peptide (human α‐CGRP) was studied in rat thoracic aortic rings preconstricted with noradrenaline (10−7 m).
Vasorelaxation by human α‐CGRP was inhibited by haemogobin (10−6 m) and methylene blue (10−5 m) but was unaffected by ibuprofen (10−5 m).
Acetylcholine caused a 16 fold increase in levels of guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) with levels of adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) being unaltered. Human α‐CGRP caused a 12 fold increase in levels of cyclic GMP but, in contrast to acetylcholine, evoked a 2.5 fold rise in levels of cyclic AMP. The rises in cyclic nucleotides evoked by human α‐CGRP and acetylcholine were dependent on the presence of an intact endothelium.
NG‐nitro‐l‐arginine (l‐NOARG: 10−5 m), which inhibits nitric oxide synthase, inhibited the relaxant response to human α‐CGRP and cyclic GMP accumulation without affecting the cyclic AMP accumulation.
The data presented in this paper suggests that human α‐CGRP relaxes the rat thoracic aorta by releasing nitric oxide and stimulating guanylate cyclase. The stimulation of adenylate cyclase by human α‐CGRP probably precedes the activation of nitric oxide synthase but could be unrelated to the relaxant response.
Multiple σ binding sites in guinea‐pig and rat brain membranes: G‐protein interactions
Authors: Connick J.H. , Hanlon G. , Roberts J. , France L. , Fox P.K. , Nicholson C.D. 
Published: July 2012

Evidence is accumulating for multiple sigma (σ) sites in the mammalian CNS.
We have addressed this problem and have examined σ site — G‐protein coupling in guinea‐pig and rat brain membranes.
Ditolylorthoguanidine (DTG), (+)‐3‐(3‐hydroxyphenyl)‐N‐1‐(propyl)piperidine (3PPP) and dextromethorphan displaced [3H]‐DTG (3.4 nm) with low Hill slopes of 0.5, 0.6 and 0.6, respectively in guinea‐pig brain membranes.
In the presence of 5′‐guanylylimidodiphosphate (Gpp(NH)p; 100 μm), the specific binding of [3H]‐DTG was reduced by 36.7%, the Hill slope of 3PPP was increased to near unity, the ability of dextromethorphan to displace DTG was virtually abolished and the Hill slope for DTG remained low (0.7), indicating the presence of at least two binding sites. These data indicate that although Gpp(NH)p removes a dextromethorphan high affinity site, two DTG selective sites remain in the presence of Gpp(NH)p.
The present study suggests that DTG binds to at least three sites in guinea‐pig brain membranes, at least one of which is G‐protein linked.
In rat brain membranes, DTG displaced itself (3.4 nm) with a Hill slope near 1. 3PPP displacement of [3H]‐DTG was comparable with the guinea‐pig (Hill slope 0.5) and displaced from more than 1 site. Dextromethorphan did not displace [3H]‐DTG at concentrations below 10 μm.
The heterogeneity of σ sites appears to be less in rat than in guinea‐pig brain membranes.
Protection by Ca2+ channel blockers (nifedipine, diltiazem and verapamil) against the toxicity of oxidized low density lipoprotein to cultured lymphoid cells
Authors: Nègre‐Salvayre Anne , Salvayre Robert 
Published: July 2012

Ca2+ channel blockers from 3 different chemical classes (diltiazem, verapamil and nifedipine) were compared in their ability to inhibit low density lipoprotein (LDL) oxidation and to protect cells directly against the cytotoxicity of oxidized LDL.
LDL oxidation promoted either by u.v. radiations or by copper ions was inhibited by nifedipine (IC50 of 10 ± 2 and 4 ± 0.5 μmol 1−1, respectively) whereas diltiazem and verapamil were only poorly active or completely ineffective. As expected, LDL protected from oxidation by nifedipine (nifedipine/oxidized LDL) were much less cytotoxic than (unprotected) oxidized LDL (or than LDL oxidized in the presence of diltiazem or verapamil). The cytotoxic effect correlated well with the lipid peroxidation derivatives measured as the thiobarbituric acid reactive substances (TBARS) content of LDL oxidized in the presence of Ca2+ channel blockers, which suggests that the antioxidant effect of Ca2+ channel blockers protected cells indirectly from the cytotoxic effect of oxidized LDL.
Nifedipine also exhibited a direct cytoprotective effect against the cytotoxicity of oxidized LDL as demonstrated by incubating cells in the presence of unprotected oxidized LDL and nifedipine (IC50 of 1 ± 0.2 μmol 1−1), whereas diltiazem and verapamil did not exhibit any significant protective effect. At the concentrations used, the protective effect of nifedipine was not due to inhibition of LDL uptake by Ca2+ channel blockers.
The direct protective activity of nifedipine is probably unrelated to its antioxidant properties since it did not inhibit the cellular TBARS evoked by oxidized LDL taken up by the cells, in contrast to vitamin E.
Nifedipine (and diltiazem to a lesser extent) inhibited the slow [Ca2+]i rise induced by oxidized LDL and the subsequent cytotoxicity.
It is proposed that relatively high concentrations of nifedipine (unlike diltiazem and verapamil) protect cultured lymphoid cells against the cytotoxicity of oxidized LDL by two different mechanisms: (i) an antioxidant effect inhibiting LDL oxidation (outside the cell); (ii) a direct cytoprotective effect (at lower concentrations), the mechanism of which is unknown. These data could explain in part the mechanism of action of nifedipine in the prevention of cellular damage potentially involved in atherogenesis.
Nitric oxide is involved in 5‐HT‐induced relaxations of the guinea‐pig colon ascendens in vitro
Authors: Briejer Michel R. , Akkermans Louis M.A. , Meulemans Ann L. , Lefebvre Romain A. , Schuurkes Jan A.J. 
Published: July 2012

In the guinea‐pig colon ascendens, 5‐hydroxytryptamine (5‐HT) induces contractions, mediated by 5‐HT2, 5‐HT3 and 5‐HT4 receptors, and relaxations, through a 5‐HT1 receptor subtype, that triggers the release of an inhibitory neurotransmitter. Nitric oxide (NO) is one of the main candidates of NANC inhibitory neurotransmission in the gut. The aim of this study was to establish whether NO is involved in 5‐HT‐induced relaxations of the guinea‐pig colon ascendens.
Antagonists to block the contractile responses to 5‐HT via 5‐HT2, 5‐HT3 and 5‐HT4 receptors were present throughout the experiments and methacholine was administered to precontract the strips. Under these conditions, 5‐HT concentration‐dependently induced relaxations from 10 nm onwards (EC50 = 258 (172–387) nm). The relaxations were inhibited by metergoline (10 nm) and methiothepine (100 nm) and abolished by tetrodotoxin (TTX, 320 nm). Guanethidine (3.2 μm) did not affect them.
NG‐nitro‐l‐arginine (l‐NNA) inhibited the responses to 5‐HT (IC50 = 18.7 (13.3–26.3) μm); at the highest 5‐HT concentration a maximum inhibition of about 75% was observed with 320 μm l‐NNA. This inhibition was reversed with l‐arginine. Relaxations to glyceryl trinitrate (GTN) were not inhibited by l‐NNA.
Haemoglobin (32 μm) inhibited the relaxations to 5‐HT and GTN, but not those to isoprenaline (Iso). Methylene blue (10 μm) inhibited the relaxations to 5‐HT but did not affect those caused by GTN or Iso.
It is concluded that 5‐HT induces relaxations that involve NO. We also confirmed that 5‐HT induces these relaxations via (a) 5‐HT1 receptor subtype(s), located on neurones.
Electrophysiological effects of diprafenone, a dimethyl congener of propafenone on guinea‐pig ventricular cells
Authors: Kodama Itsuo , Suzuki Ryoko , Honjo Haruo , Toyama Junji 
Published: July 2012

The effects of diprafenone and propafenone on transmembrane action potential were examined and compared in papillary muscles and single ventricular myocytes isolated from guinea‐pig hearts.
In papillary muscles, both diprafenone and propafenone ≥ 10−6 m caused a significant and dose‐dependent decrease in the maximum upstroke velocity () of the action potential.
In the presence of either drug, trains of stimuli at rates ≥ 0.1 Hz led to an exponential decline in . A time constant (τR) for recovery from the use‐dependent block was 15.5 s for diprafenone and 8.8 s for propafenone.
The use‐dependent block of with diprafenone was enhanced when the resting potential was depolarized by high (8, 10 mm) [K+]o, whereas that with propafenone was virtually unchanged. τR with diprafenone was shortened by the depolarization, while that with propafenone was rather prolonged.
In single myocytes perfused with diprafenone or propafenone, 10 ms conditioning clamp to 0 mV caused a significant decrease in of subsequent action potential. A prolongation of the clamp pulse duration resulted in a modest enhancement of the inhibition with diprafenone, while a large enhancement of the inhibition occurred with propafenone.
These findings suggest that diprafenone, like propafenone, may block the sodium channel during both the activated and inactivated states. The relative contribution of inactivation block is less important for diprafenone than for propafenone. The different voltage‐dependence of use‐dependent block with diprafenone from propafenone would contribute to its high antiarrhythmic potency.
Changes in purinergic responses of the rabbit isolated central ear artery after chronic electrical stimulation in vivo
Authors: Maynard K.I. , Loesch A. , Burnstock G. 
Published: July 2012

The effect of chronic (4–16 days) electrical stimulation (5 Hz, 0.3 ms, 4–10 V) of the great auricular nerve in vivo on sympathetic cotransmission in the rabbit isolated central ear artery was examined.
Chronic stimulation had no significant effect on frequency‐dependent (4–60 Hz) neurogenic contractions or contractile responses induced by exogenous noradrenaline (0.1–300 μm).
In contrast, contractions induced by exogenous α,β‐methylene ATP (10.0 μm) were significantly decreased in preparations from 16‐day stimulated animals in comparison with sham‐operated, 4‐day and 8‐day chronically stimulated animal groups.
It is concluded that chronic electrical stimulation of nerves supplying the ear artery may lead to the selective alteration of postjunctional P2x‐purinoceptor mechanisms, while the effects mediated by postjunctional α1‐adrenoceptors remain unchanged.
A possible role of the L‐arginine‐nitric oxide pathway in the modulation of cholinergic transmission in the guinea‐pig taenia coli
Authors: Knudsen M.A. , Tøttrup A. 
Published: July 2012

The role of the l‐arginine‐nitric oxide (NO) pathway for non‐adrenergic, non‐cholinergic (NANC) relaxation of the guinea‐pig taenia coli was studied by recording isometric tension in response to transmural field stimulation (TMS).
In preparations precontracted with prostaglandin F2α (PGF2α, 10−6 m), TMS induced frequency‐dependent responses of the muscle strips which could be abolished by tetrodotoxin (10−6 m). NG‐nitro‐l‐arginine (l‐NNA, 10−4 m), an l‐arginine analogue, and potent inhibitor of NO synthesis, stereospecifically inhibited maximum relaxations, but did not shift the frequency‐response curve. Preincubation with NG‐nitro‐d‐arginine (d‐NNA, 10−4 m), atropine (10−6 m) plus l‐NNA (10−4 m), or atropine (10−6 m) alone, had no influence on the frequency‐response characteristics.
l‐NNA (10−7−10−4 m) concentration‐dependently inhibited relaxations in PGF2α (10−6 m) precontracted strips in response to TMS, but did not abolish relaxations. Preincubation with l‐arginine (10−4 m) inhibited these effects of l‐NNA. l‐NNA (10−4 m) had no effect on the inhibitory response during TMS in strips preincubated with atropine (10−6 m).
The relaxation induced by sodium nitroprusside and forskolin (10−9−10−4 m) was not influenced by l‐NNA (10−4 m) preincubation as expressed by identical pD2 and Emax values.
Contractions induced by PGF2α (10−9−10−4 m) and carbachol (10−9−10−4 m) were not affected by pretreatment with l‐NNA (10−4 m), as expressed by identical pD2 and Emax values.
In conclusion, the l‐arginine‐NO pathway seems to play a role in the NANC innervation of the guinea‐pig taenia coli. The inhibitory effect of NO or a NO‐like compound depends on the integrity of the cholinergic pathways and it is proposed that this compound exerts its effects prejunctionally on cholinergic nerves, by inhibiting the release of acetylcholine.
Iron‐sulphur cluster nitrosyls, a novel class of nitric oxide generator: mechanism of vasodilator action on rat isolated tail artery
Authors: Flitney F.W. , Megson I.L. , Flitney D.E. , Butler A.R. 
Published: July 2012

Two iron‐sulphur cluster nitrosyls have been investigated as potential nitric oxide (NO·) donor drugs (A: tetranitrosyltetra‐μ3‐sulphidotetrahedro‐tetrairon; and B: heptanitrosyltri‐μ3‐thioxotetraferrate(1‐)). Both compounds are shown to dilate precontracted, internally‐perfused rat tail arteries.
Bolus injections (10 μl) of compound A or B generate two kinds of vasodilator response. Doses below a critical threshold concentration (DT) evoke transient (or T‐type) responses, which resemble those seen with conventional nitrovasodilators. Doses > DT produce sustained (or S‐type) responses, comprising an initial, rapid drop of pressure, followed by incomplete recovery, resulting in a plateau of reduced tone which can persist for several hours.
T‐ and S‐type responses are attenuated by ferrohaemoglobin (Hb) and by methylene blue (MB), but not by inhibitors of endothelial NO· synthase. Addition of either Hb or MB to the internal perfusate can restore agonist‐induced tone when administered during the plateau phase of an S‐type response. Moreover, subsequent removal of Hb causes the artery to re‐dilate fully.
We conclude that T‐ and S‐type responses are both mediated by NO·. It is postulated that S‐type responses represent the sum of two vasodilator components: a reversible component, superimposed upon a non‐recoverable component. The former is attributed to free NO·, preformed in solution at the time of injection; and the latter to NO· generated by gradual decomposition of a ‘store’ of iron‐sulphur‐nitrosyl complexes within the tissue. This hypothesis is supported by histochemical studies which show that both clusters accumulate in endothelial cells.
Blockade of 5‐HT3 receptor‐mediated currents in dissociated frog sensory neurones by benzoxazine derivative, Y‐25130
Authors: Yakushiji Takashi , Akaike Norio 
Published: July 2012

The effect of Y‐25130, ((±)‐N‐(1‐azabicyclo[2.2.2]oct‐3‐yl)‐6‐chloro‐4‐methyl‐3‐oxo‐3,4‐dihydro‐2H‐1,4‐benzoxazine‐8‐carboxamide hydrochloride), a high affinity 5‐hydroxytryptamine3 (5‐HT3) receptor ligand, was examined on the 5‐HT‐induced response in dissociated frog dorsal root ganglion (DRG) neurones by use of the extremely rapid concentration‐jump (“concentration‐clamp’) and the conventional whole‐cell patch‐clamp techniques.
5‐HT induced a rapid transient inward current associated with an increase in membrane conductance at a holding potential of — 70 mV. The current amplitude increased sigmoidally as 5‐HT concentration increased. The half‐maximum value (Ka) and the Hill coefficient estimated from the concentration‐response curve were 1.7 × 10−5 m and 1.7, respectively.
The current‐voltage (I—V) relationship of 5‐HT‐induced current (I5‐HT) showed inward rectification at potentials more positive than — 40 mV. The reversal potential (E5‐HT) was — 11 mV. The E5‐HT value was unaffected by total replacement of intracellular K+ by Cs+, indicating that the 5‐HT‐gated channels might be large cation channels.
Both the activation and inactivation phases of I5‐HT were single exponentials. The time constants of activation and inactivation (τa and τi) decreased with increasing 5‐HT concentration.
The 5‐HT response was mimicked by a selective 5‐HT3 receptor agonist, 2‐methyl‐5‐HT, but the maximum response induced was approximately 25% that of 5‐HT. The 5‐HT response was reversibly antagonized by the 5‐HT3 receptor antagonists, ICS 205–930, metoclopramide and Y‐25130, but not by a 5‐HT1A receptor antagonist, spiperone, and a 5‐HT2 receptor antagonist, ketanserin. The half‐inhibition concentrations (IC50) were 4.9 × 10−10 m for Y‐25130, 4.8 × 10−10 m for ICS 205–930 and 8.6 × 10−9 m for metoclopramide.
Y‐25130 (5 × 10−10 m) caused a rightward shift of the concentration‐response curve for 5‐HT while decreasing the maximum response.
The results suggest that Y‐25130 is a potent antagonist of the 5‐HT3 receptor‐channel complex.