bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of intravenous anaesthetic agents on fast inhibitory oscillations in the rat hippocampus in vitro
Authors: Whittington M.A. , Jefferys TJ.G.R. , Traub R.D. 
Published: July 2012

General anaesthetic agents prevent awareness of sensory input and subsequent recall of sensory events after administration. The mechanisms involved in higher sensory processing, including awareness and recall, are not fully elucidated. However, fast oscillations in neuronal activity in the 20–80 Hz (gamma) range have been strongly implicated. Here we have investigated the effects of two anaesthetic agents and a sedative/hypnotic drug on these oscillations.
Trains of fast oscillations, shown previously to be shaped by γ‐aminobutyric acid (GABAA) receptor activation, were evoked by pressure ejection of L‐glutamate (10 mM) onto the perisomatic region of hippocampal area CA1 in the presence of 3‐((R)‐2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonic acid (R‐CPP), 50 μm, 6‐nitro‐7‐sulphamoylbenzo[f]quinoxaline‐2,3‐dione (NBQX), 50 μm and 2‐hydroxysaclofen, 0.2 mM.
Thiopentone (10–200 μm) and propofol (0.5–10 μm) dose‐dependently decreased both the maximum oscillation frequency, by approx. 90%, and the incidence of evoked rhythmic oscillations by approx. 60%. Diazepam (0.05‐1 μm) decreased maximum oscillation frequency by about 40% but did not affect the incidence of evoked oscillations.
The similar effects of thiopentone and propofol were mediated by both a large (about 600%) increase in the decay constant (τD) of GABAA receptor‐mediated inhibitory postsynaptic currents (i.p.s.cs) and a bicuculline‐sensitive leak current. The two drugs had differing effects on i.p.s.c. amplitude. Diazepam caused a small increase in τD (about 170%) and did not alter leak currents at the doses used.
Effects of the anaesthetic agents were seen on the above measurements at similar concentrations to those estimated in the CNS during clinical and veterinary anaesthesia. We suggest that the effects on fast oscillations associated with cognition may contribute to the mechanism by which these agents produce general anaesthesia.
The effect of ovariectomy on depressed contractions to phenylephrine and KC1 and increased relaxation to acetylcholine in isolated aortic rings of female compared to male rabbits
Authors: Sánchez Alicia , Gómez María de Jesús , Dorantes Ana Luisa , Rosales José Luis , Pastelín Gustavo , Díaz Vicente , Posadas Francisco , Escalante Bruno 
Published: July 2012

Differences in vascular responses to phenylephrine, acetylcholine (ACh) and potassium chloride (KC1) were studied in rabbit aorta from female and male rabbits, in the absence and presence of an inhibitor of nitric oxide (NO) production, NG‐nitro‐l‐arginine methyl ester (L‐NAME, 100 μm).
Phenylephrine and KC1‐induced contractions, were significantly reduced in amplitude (P < 0.01) in the rings from female rabbits compared to those from male rabbits.
ACh‐induced relaxation was greater (P < 0.01) in aortic rings from females than from males.
Incubation of the rings with L‐NAME abolished the phenylephrine‐induced contraction differences between rings from male and female rabbits.
Ovariectomy eliminated the differences in vascular responses to phenylephrine, KC1 and ACh of aortic rings from the female rabbits.
Both basal and ACh‐stimulated release of nitrites from aortic rings was greater (P < 0.01) in vascular tissue from female than male rabbits.
These results indicate that differences in vascular reactivity in aortic rings from male and female rabbits may be associated with a higher release of NO, resulting in an increased vasodilator response in the female rabbits.
Sources of calcium and α1‐adrenoceptor‐mediated contraction in rat tail artery
Authors: Tabernero Antonia , Vivas Nuria M. , Vila Elisabet 
Published: July 2012

The relative importance of intracellular and extracellular Ca2+ on α1‐adrenoceptor‐mediated contraction by noradrenaline and St‐587 has been studied and correlated with the binding characteristics in intact tail artery from Sprague‐Dawley rats.
Noradrenaline and St‐587 behaved as full agonists inducing a concentration‐dependent vasoconstriction.
Nifedipine (1 μm and 10 μm) blocked by 50% (P < 0.001) and 75% (P < 0.001) respectively, the maximum contraction (Emax) induced by St‐587. Nevertheless, to reach 40% inhibition of Emax on noradrenaline responses (P < 0.01), 10 μm nifedipine was necessary.
Both agonists induced a concentration‐dependent accumulation of inositol phosphates. Noradrenaline behaved as a full agonist and St‐587 as a partial agonist for this response.
[3H]‐prazosin binding to intact tail artery rings was saturable and of high affinity (KD = 4.44 ± 0.46 nM; Bmax = 36.35 ± 4.22 fmol mg−1 tissue).
Competition curves for inhibition of specific [3H]‐prazosin binding by WB‐4101 suggest that the rat tail artery contains two α1‐adrenoceptor subtypes in an approximate ratio of 60:40.
After irreversible alkylation of α1B‐adrenoceptors with 100 μm chloroethylclonidine (CEC), nifedipine (1 μm) influenced to a greater extent the St‐587‐ than the noradrenaline‐induced contraction.
Our results indicate that the degree of participation of intracellular and extracellular Ca2+ sources, on the α1‐adrenoceptor‐mediated contraction, depends on the agonist used. The two α1‐adrenoceptor subtypes observed in binding experiments seem to be unrelated to the Ca2+ sources used for contraction.
Effects of agents which elevate cyclic AMP on guinea‐pig eosinophil homotypic aggregation
Authors: Teixeira M.M. , Rossi A.G. , Giembycz M.A. , Hellewell P.G. 
Published: July 2012

Eosinophil recruitment and activation in inflamed tissue is thought to play an important role in the pathophysiology of allergic diseases. Experimental evidence suggests that elevating cyclic AMP is an effective means of reducing eosinophil recruitment in vivo and may therefore have therapeutic benefit. In the present study, we have assessed the capacity of cyclic AMP‐elevating agents to modulate guinea‐pig eosinophil homotypic aggregation, a CD18‐dependent process, which may be an important component of eosinophil function in vivo.
Prostaglandin E1 (PGE1, 10−10 to 10−6 m) inhibited platelet activating‐factor (PAF)‐ and C5a‐induced eosinophil aggregation in a concentration‐dependent manner. However, PAF‐induced responses were more potently and more effectively inhibited by PGE1. The inhibitory effects of PGE1 on PAF‐induced aggregation were reversed by pretreatment of eosinophils with the protein kinase A inhibitors H89 and KT5720.
The β2‐adrenoceptor agonists, salbutamol and salmeterol, concentration‐dependently inhibited eosinophil aggregation induced by C5a and PAF and, again, PAF‐induced responses were more effectively reduced. The inhibitory effect of salmeterol was mediated by β‐adrenoceptors, as assessed by the reversal after pretreatment with propranolol.
Rolipram, a selective phosphodiesterase 4 (PDE4) inhibitor, also attenuated PAF‐ and C5a‐induced aggregation and at a low concentration which did not affect aggregation per se, had a synergistic effect with PGE1 and salbutamol to suppress this response.
Activation of eosinophils with PAF or C5a induced a small but significant increase in the level of CD18 expression on the eosinophil surface. PGE1 (10−7 m) decreased PAF‐ and C5a‐induced upregulation of CD18 by 93% and 62%, respectively.
These results demonstrate that cyclic AMP‐elevating agents effectively inhibit eosinophil aggregation, a CD18‐dependent functional response. Because CD18 has been shown to be important for eosinophil recruitment to inflamed tissue in vivo, our findings may be of relevance to the efficacy of cyclic AMP‐elevating agents at inhibiting eosinophil trafficking.
Effects of caffeine and 3‐isobutyl‐1‐methylxanthine on voltage‐activated potassium currents in vertebrate neurones and secretory cells
Authors: Reiser Michelle A. , D'Souza Theresa , Dryer Stuart E. 
Published: July 2012

The effects of caffeine and 3‐isobutyl‐1‐methylxanthine (IBMX) on voltage‐activated K+ currents were examined by use of patch clamp recording techniques in dissociated chick autonomic ganglion neurones, chick pineal cells and rat anterior pituitary cells.
In chick ciliary ganglion neurones, caffeine (0.1–10 mM) produced a robust blockade of delayed rectifier K+ currents (IDR). Blockade was rapid in onset and concentration‐ and voltage‐dependent. Caffeine produced greater inhibition with larger depolarizing voltage pulses. Similar inhibition of IDR was observed in excised outside‐out ‘maxi‐patches’ indicating a direct effect on the K+ channels. Caffeine also inhibited IDR in chick sympathetic neurones, chick pineal cells and rat anterior pituitary cells.
Application of 10 mM caffeine caused inhibition of transient A‐currents (IA) in chick ciliary ganglion neurones. Inhibition of IA was voltage‐dependent with greater inhibition observed at more positive command potentials. Application of 1 mM caffeine did not cause inhibition of IA.
Application of 1 mM IBMX, a structural analogue of caffeine, caused inhibition of IDR and IA in chick ciliary ganglion neurones. The voltage‐dependence of the inhibition of both currents was qualitatively different from that observed with caffeine. The inhibitory effects of 1 mM IBMX and 10 mM caffeine on IDR and IA were additive.
Direct inhibition of voltage‐activated K+ currents can potentially produce significant secondary effects on intracellular free Ca2+. These results indicate that caution must be used in the design and interpretation of experiments in which millimolar concentrations of caffeine or IBMX are used in pharmacological studies of intracellular Ca2+ dynamics or other second messenger mechanisms.
Delayed protection against ischaemia‐induced ventricular arrhythmias and infarct size limitation by the prior administration of Escherichia coli endotoxin
Authors: Song Wu , Furman Brian L. , Parratt James. R. 
Published: July 2012

Bacterial endotoxin (lipopolysaccharide derived from Escherichia coli) was injected intraperitoneally in conscious rats in doses ranging from 0.5 to 2.5 mg kg−1. At various times afterwards the animals were anaesthetized and subjected to a 30 min period of left coronary artery occlusion.
Under these conditions the severity of ventricular arrhythmias was markedly suppressed, in comparison with saline‐injected controls, but this was particularly marked with the higher doses (1.5 and 2.5 mg kg−1); the number of ventricular premature beats was reduced from 1687 ± 227 over the 0.5 h coronary artery occlusion period to 190 ± 46 in those rats administered 2.5 mg kg−1 endotoxin 8 h previously (P < 0.05). The duration of ventricular tachycardia was also significantly reduced (138 ± 26 s to 8.9 ± 4.2 s; P < 0.01) and there was a reduction in the incidence of ventricular fibrillation (from 56% to 10%).
The time course of this protection was studied following the administration of a single dose of 2.5 mg kg−1 of endotoxin by anaesthetizing rats 4, 8 or 24 h later. Protection was apparent at each time but was particularly marked at 8 h.
No rat given the highest dose of endotoxin (32 in all) died as a result of ventricular fibrillation, or from any other cause, during an occlusion, in contrast to a 26% mortality in the controls (P < 0.01).
Infarct size, measured following a 30 min period of coronary artery occlusion followed by a 3 h reperfusion period, was reduced both 8 and 24 h after the administration of 2.5 mg kg−1 endotoxin (reductions of 24.3 and 23.1% respectively; P < 0.05). Endotoxin had no significant effect on the area at risk.
The beneficial effects of endotoxin on infarct size and on ventricular arrhythmias were markedly attenuated by the prior administration of dexamethasone, 3 mg kg−1 given 1 h prior to endotoxin administration. Dexamethasone itself reduced infarct size (P < 0.05) but had no direct effect on arrhythmia severity following coronary artery occlusion.
The mechanisms of this ‘cross‐tolerance’ induced by bacterial endotoxin against ischaemia‐reperfusion injury remain to be elucidated but the most likely mechanisms appear to be the induction of protective enzymes or proteins (e.g. nitric oxide synthase, cyclo‐oxygenase (COX) 2) probably mediated by cytokine release.
Substance P and capsaicin‐induced mechanical hyperalgesia in the rat knee joint; the involvement of bradykinin B1 and B2 receptors
Authors: Davis A.J. , Perkins M.N. 
Published: July 2012

Substance P (SP) and capsaicin induced a mechanical hyperalgesia when injected into rat knee joints.
The NK1 receptor antagonists CP 99994 (10–100 nmol) and RP 67580 (0.1‐1 nmol) blocked the development of, and also reversed, SP‐induced hyperalgesia. Capsaicin (10 nmol)‐induced hyperalgesia was blocked by capsazepine (0.5‐5 nmol).
Capsaicin‐induced hyperalgesia was prevented and reversed by the NK1 receptor antagonists CP 99994 (100 nmol) and RP 67580 (1 nmol).
The bradykinin B2 receptor antagonist icatibant (5 pmol) blocked the development of both SP and capsaicin‐induced hyperalgesia. Icatibant (100 pmol kg−1, i.v.) also reversed an established SP and capsaicin‐induced hyperalgesia.
Both low dose SP (1 nmol) and capsaicin (1 nmol)‐induced hyperalgesia were potentiated by the kininase II inhibitor captopril (100 μg).
The B1 receptor antagonists desArg9Leu8‐bradykinin (BK) (0.5‐5 nmol) and desArg10[Hoe 140] (5–50 pmol) only blocked the development of SP‐induced hyperalgesia for 30 min after administration. desArg9Leu8‐BK (10 nmol kg−1 i.v.) did not reverse an established SP‐induced hyperalgesia.
Capsaicin‐induced hyperalgesia was blocked by desArg9Leu8‐BK (0.5 nmol) and this antagonist also reversed an established capsaicin‐induced hyperalgesia.
Interleukin‐1 receptor antagonist (IL‐1ra 0.1 μg) reduced the development of SP‐induced hyperalgesia up to 4 h after administration, but did not reverse an established hyperalgesia. IL‐1ra (0.1 μg) also blocked the development of and reversed an established capsaicin‐induced hyperalgesia.
Indomethacin pretreatment (1 mg kg−1, s.c.) did not reduce the development of either SP‐ or capsaicin‐induced hyperalgesia but following indomethacin‐pretreatment desArg9Leu8‐BK (10 nmol kg−1, i.v.) failed to reverse a capsaicin‐induced hyperalgesia.
In conclusion, both SP and capsaicin can induce behavioural hyperalgesia when injected into the knee joint of rats. In addition, blockade of NK1, bradykinin B1, B2 and IL‐1β receptors can substantially modulate this hyperalgesia.
Thromboxane A2 agonist modulation of excitatory synaptic transmission in the rat hippocampal slice
Authors: Hsu Kuei‐Sen , Kan Wai‐Ming 
Published: July 2012

The effects of the selective thromboxane A2 (TXA2) receptor agonist I‐BOP on neuronal excitability and synaptic transmission were studied in the CA1 neurones of rat hippocampal slices by an intracellular recording technique.
Superfusion of I‐BOP (0.5 μm) resulted in a biphasic change of the excitatory postsynaptic potential (e.p.s.p.), which was blocked by pretreatment with SQ 29548, a specific antagonist of TXA2 receptors. The inhibitory phase of I‐BOP on the e.p.s.p. was accompanied by a decrease in neuronal membrane input resistance.
The sensitivity of postsynaptic neurones to glutamate receptor agonists, α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) or N‐methyl‐D‐aspartate (NMDA), was unchanged by I‐BOP (0.5 μm) pretreatment.
Bath application of Ba2+ (0.5 mM) prevented both the I‐BOP‐induced reduction of the neuronal membrane input resistance and the blockade of e.p.s.p. induced by I‐BOP.
Intracellular dialysis of the hippocampal CA1 neurones with GDP (10 mM) significantly attenuated the I‐BOP inhibition of e.p.s.p. and membrane input resistance. Incubation of the slices with either pertussis toxin (PTX, 5 μg ml−1 for 12 h) or cholera toxin (CTX, 5 μg ml‐1 for 12 h) did not affect the biphasic action of I‐BOP on the e.p.s.p. or the reduction of membrane input resistance induced by I‐BOP.
Pretreatment of the slices with the protein kinase C (PKC) inhibitor, NPC‐15437 (20 μm), abolished the biphasic modulation by I‐BOP (0.5 μm) of the e.p.s.p. Intracellular application of a specific PKC inhibitor, PKCI 19–36 (20 μm), completely inhibited the I‐BOP reduction of e.p.s.p. The specific cyclic AMP‐dependent protein kinase (PKA) inhibitor, Rp‐cyclic adenosine 3′,5′‐monophosphate (Rp‐cyclic AMPS, 25 μm), had no effect on the I‐BOP action.
In this study we have demonstrated, for the first time, the existence of functional TXA2 receptors in the hippocampus which mediate the effects of a TXA2 agonist on neuronal excitability and synaptic transmission. Activation of the presynaptic TAX2 receptors may stimulate the release of glutamate. Conversely, activation of postsynaptic TXA2 receptors leads to inhibition of synaptic transmission resulting from a decrease in the membrane input resistance of the neurones. The pre‐ and postsynaptic actions of the TXA2 agonist are both mediated by PTX‐ and CTX‐insensitive G‐protein‐coupled activation of PKC pathways.
Stimulation of the hypothalamo‐pituitary‐adrenal axis in the rat by the type 4 phosphodiesterase (PDE‐4) inhibitor, denbufylline
Authors: Hadley A.J. , Kumari M. , Cover P.O. , Osborne J. , Poyser R. , Flack J.D. , Buckingham J.C. 
Published: July 2012

Preliminary studies in our laboratories showed that the synthetic xanthine analogue denbufylline, a selective type 4 phosphodiesterase (PDE‐4) inhibitor, is a potent activator of the hypothalamo‐pituitary‐adrenal (HPA) axis when given orally to adult male rats. This paper describes the results of experiments in which well established in vivo and in vitro models were used to (a) examine further the effects of denbufylline on HPA function and (b) identify the site and mode of action of the drug within the axis.
In vivo, administration of denbufylline (0.1–2.5 mg kg−1, i.p.) produced a significant increase in the serum corticosterone concentration; maximal responses were attained at a dose of 1.0 mg kg−1 (P < 0.01 vs. vehicle control, Scheffe's test). However, when denbufylline was administered by intracerebroven‐tricular injection (0.05‐1 μg kg−1) it failed to influence significantly the serum corticosterone concentration (P > 0.05 vs. vehicle control, Scheffe's test). The adrenocortical responses to peripheral injections of denbufylline (1 mg kg−1, i.p.) were reduced in rats in which the secretion of endogenous corticotrophin releasing factors (CRFs) from the hypothalamus was blocked pharmacologically (P < 0.01 vs. controls, Scheffe's test). However, denbufylline (0.1 mg kg−1, i.p.) potentiated the significant (P < 0.01) increases in serum corticosterone concentration provoked in ‘CRF blocked rats’ by hypothalamic extract (5 hypothalamic extracts kg−1, i.v.) although it failed to influence (P > 0.05) the relatively moderate increases in corticosterone secretion evoked by CRH‐41 (2 mg kg−1, i.v.).
In vitro, denbufylline (0.01‐1 mM) evoked small but significant (P < 0.05) increases in the release of ACTH from rat anterior pituitary segments; furthermore, at these and lower concentrations (0.01 μm‐1 mM), it potentiated the adrenocorticotrophic responses to sub‐maximal concentrations of hypothalamic extract (P < 0.01) and forskolin (0.1 mM, P < 0.01) but not those to CRH‐41 (10 nM) or 8‐bromo‐cyclic AMP (1–100 μm). In addition, denbufylline (0.1 mM) increased the anterior pituitary cyclic AMP content (P < 0.05) and potentiated the rises in tissue content of the cyclic nucleotide induced by hypothalamic extract (0.1 hypothalamic equivalents ml−1, P < 0.01) and forskolin (0.1 mM, P < 0.01) but not by CRH‐41 (10 nM, P < 0.05). By contrast, denbufylline (1 μm‐1 mM) failed to influence the release of AVP from rat isolated hypothalami and stimulated the secretion of CRH‐41 (P < 0.01) release only at the highest concentration tested (1 mM).
The results suggest that the stimulatory actions of denbufylline on the hypothalamo‐pituitary‐adrenocortical axis are exerted predominantly at the level of the anterior pituitary gland and that they may be attributed, at least in part, to inhibition of type 4 phosphodiesterase enzymes.
Inhibition by fenamates of calcium influx and proliferation of human lymphocytes
Authors: Kankaanranta H. , Luomala M. , Kosonen O. , Moilanen E. 
Published: July 2012

Flufenamic and tolfenamic acids have recently been shown to inhibit receptor‐mediated calcium influx in human neutrophils. The present work was designed to study the effects of these two nonsteroidal anti‐inflammatory drugs on human peripheral blood lymphocyte activation.
Peripheral blood mononuclear cells (PBMNCs; containing 90% lymphocytes) were stimulated by mitogen concanavalin A (Con A) or by a combination of an inhibitor of microsomal Ca2+‐adenosine triphosphatase thapsigargin (TG) and phorbol myristate acetate (PMA). The effects of the two fenamates on cell proliferation were compared with respective changes in calcium metabolism.
Flufenamic and tolfenamic acids (10–100 μm) inhibited both Con A and TG+PMA‐induced [3H]‐thymidine incorporation in a dose‐dependent manner. At the same concentration range, the two fenamates inhibited the increase in intracellular free calcium concentration induced by Con A or TG+PMA. This effect was due to inhibition of calcium influx whereas calcium release from intracellular stores remained unaltered.
The inhibition of divalent cation influx was confirmed by showing that fenamates inhibited TG+PMA‐induced Mn2+ influx.
The inhibitory effects of fenamates on PBMNC proliferation and Ca2+ influx were qualitatively similar with those of SK&F 96365, an earlier known inhibitor of receptor‐mediated calcium entry. Ketoprofen, a chemically different prostaglandin synthetase inhibitor did not show similar suppressive effects on PBMNCs.
The data suggest that flufenamic and tolfenamic acids suppress proliferation of human peripheral blood lymphocytes by a mechanism which involves inhibition of Ca2+ influx and is not related to inhibition of prostanoid synthesis.
α‐Adrenoceptor and opioid receptor modulation of clonidine‐induced antinociception
Authors: Sierralta F. , Naquira D. , Pinardi G. , Miranda H.F. 
Published: July 2012

The antinociceptive action of clonidine (Clon) and the interactions with α1, α2 adrenoceptor and opioid receptor antagonists was evaluated in mice by use of chemical algesiometric test (acetic acid writhing test).
Clon produced a dose‐dependent antinociceptive action and the ED50 for intracerebroventricular (i.c.v.) was lower than for intraperitoneal (i.p.) administration (1 ng kg−1 vs 300 ng kg−1). The parallelism of the dose‐response curves indicates activation of a common receptor subtype.
Systemic administration of prazosin and terazosin displayed antinociceptive activity. Pretreatment with prazosin produced a dual action: i.c.v. Clon effect did not change, and i.p. Clon effect was enhanced. Yohimbine i.c.v. or i.p. did not induce antinonciception, but antagonized Clon‐induced activity. These results suggest that α1‐ and α2‐adrenoceptors, either located at the pre‐ and/or postsynaptic level, are involved in the control of spinal antinociception.
Naloxone (NX) and naltrexone (NTX) induced antinociceptive effects at low doses (μg kg−1 range) and a lower antinociceptive effect at higher doses (mg kg−1 range). Low doses of NX or NTX antagonized Clon antinociception, possibly in relation to a preferential μ opioid receptor antagonism. In contrast, high doses of NX or NTX increased the antinociceptive activity of Clon, which could be due to an enhanced inhibition of the release of substance P.
The results obtained in the present work suggest the involvement of α1‐, α2‐adrenoceptor and opioid receptors in the modulation of the antinociceptive activity of clonidine, which seems to be exerted either at spinal and/or supraspinal level.