Home About us Contact
|
Home About us Contact | ||
|
|
||
Acute Application (acute + application)
Selected AbstractsIso-S -petasin, a hypotensive sesquiterpene from Petasites formosanus, depresses cardiac contraction and intracellular Ca2+ transients in adult rat ventricular myocytesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2003Lucy B. Esberg ABSTRACT Petasites formosanus is an indigenous species of the medicinal plant Petasites which has been used to treat hypertension. Both S -petasin and its isoform iso-S -petasin have been shown to be the effective ingredients in P. formosanus. However, their effect on heart function has not been revealed. This study was to examine the effect of iso-S -petasin on cardiac contractile function at the myocyte level. Ventricular myocytes were isolated from adult rat hearts and were stimulated to contract at 0.5 Hz under 1.0 mm extracellular Ca2+. Contractile properties were evaluated using an lonOptix MyoCam system including peak shortening (PS), time to PS (TPS), time to 90% re-lengthening (TR90) and maximal velocity of shortening/re-lengthening (±dL/dt). Intracellular Ca2+ properties were assessed by fura-2 and presented as Ca2+ -induced Ca2+ release (CICR) and intracellular Ca2+ decay. Acute application of iso-S -petasin (10,7 to 10,4 M) elicited a concentration-dependent inhibition in PS and CICR, with maximal inhibitions of 51.0% and 31.0%, respectively. iso-S -petasin also induced a concentration-dependent inhibition of ± dL/dt without affecting TPS, TR90, baseline intracellular Ca2+ level or intracellular Ca2+ decay. Elevation of extracellular Ca2+ from 1.0 mm to 2.7 mm significantly antagonized the iso-S -petasin-induced depression in PS and CICR. These results demonstrated a direct depressant action of iso-S -petasin on ventricular contraction, which may work in concert with its antihypertensive action to reduce the cardiac load. The iso-S -petasin-induced decrease in CICR may play a role in its cardiac depressant effect. [source] Nicotine withdrawal suppresses nicotinic modulation of long-term potentiation induction in the hippocampal CA1 regionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2006Yoshihiko Yamazaki Abstract We have previously reported that acute and chronic nicotine exposure lower the threshold for long-term potentiation (LTP) induction in the rat hippocampal CA1 region, and acute application of nicotine in the chronic-nicotine-treated hippocampus further reduces the threshold. However, it is unknown how withdrawal from chronic nicotine exposure affects the induction of LTP. Here, we show that, following nicotine withdrawal, the threshold for LTP induction fluctuates before returning to the basal level and acute nicotine is no longer effective in lowering the threshold at 4 days after withdrawal. Chronic nicotine-induced enhancement of N -methyl- d -aspartate receptor responses slowly diminishes and returns to the control level by 8 days of withdrawal. In 4-day-withdrawn hippocampi, there is functional up-regulation of postsynaptic ,7 nicotinic acetylcholine receptors (nAChRs) on interneurons in the stratum radiatum, whereas the release of ,-aminobutyric acid from their terminals is reduced. In both control and chronic nicotine-exposed hippocampi, acute nicotine depresses monosynaptic inhibitory postsynaptic currents recorded in pyramidal cells but has almost no effect at 4 days of withdrawal. The lack of effect is due, at least in part, to the loss of a presynaptic nicotine effect. These withdrawal-induced changes are accompanied by decreases in normal nicotine-induced enhancement of N -methyl- d -aspartate receptor responses, which may be responsible for the lack of acute nicotine-mediated facilitation of LTP induction in 4-day-withdrawn hippocampi. These withdrawal-induced changes may contribute to the cellular basis of unpleasant withdrawal symptoms and, thus, nicotine dependence. [source] Mechanisms Associated with the Negative Inotropic Effect of Deuterium Oxide in Single Rat Ventricular MyocytesEXPERIMENTAL PHYSIOLOGY, Issue 2 2000K. Hongo Deuterium oxide (D2O) is known to cause a negative inotropic effect in muscle although the mechanisms associated with this response in cardiac muscle are not well understood. We studied the effects of D2O in single rat ventricular myocytes in order to characterise the mechanisms associated with its negative inotropic effect and to assess its possible use as an acute modulator of microtubules. D2O rapidly reduced the magnitude of contraction in rat ventricular myocytes, and there was some recovery of contraction in the presence of D2O. Colchicine, an agent known to depolymerise microtubules, did not modify the effect of D2O. D2O decreased the L-type Ca2+ current (ICa), measured under whole cell and perforated patch clamp conditions. Slowing of the time to peak and a delay in inactivation of ICa were observed. Intracellular calcium ([Ca2+]i) and sodium ([Na+]i) were measured using the fluorescent indicators fura-2 and SBFI, respectively. The fall in contraction upon exposure to D2O was not associated with a fall in the [Ca2+]i transient; this response is indicative of a reduction in myofilament Ca2+ sensitivity. Both the [Ca2+]i transient and [Na+]i increased during the partial recovery of contraction in the presence of D2O. We conclude that a decrease in the myofilament sensitivity for Ca2+ and a reduction in Ca2+ influx via ICa are principally responsible for the negative inotropic effect of D2O in cardiac muscle. We found no evidence to explain the negative inotropic effect of D2O in terms of microtubule proliferation. In addition we suggest that acute application of D2O is not a useful procedure for the investigation of the role of microtubules in excitation-contraction coupling in cardiac muscle. [source] Long-term modulation of glucose utilization by IL-1, and TNF-, in astrocytes: Na+ pump activity as a potential target via distinct signaling mechanismsGLIA, Issue 1 2002Céline Véga Abstract Interleukin-1, (IL-1,) and tumor necrosis factor-, (TNF-,) markedly stimulate glucose utilization in primary cultures of mouse cortical astrocytes. The mechanism that gives rise to this effect, which takes place several hours after application of cytokine, has remained unclear. Experiments were conducted to identify the major signaling cascades involved in the metabolic action of cytokine. First, the selective IL-1 receptor antagonist (IL-1ra) prevents the effect of IL-1, on glucose utilization in a concentration-dependent manner, whereas it has no effect on the action of TNF-,. Then, using inhibitors of three classical signaling cascades known to be activated by cytokines, it appears that the PI3 kinase is essential for the effect of both IL-1, and TNF-,, whereas the action of IL-1, also requires activation of the MAP kinase pathway. Participation of a phospholipase C-dependent pathway does not appear critical for both IL-1, and TNF-,. Inhibition of NO synthase by L-NAME did not prevent the metabolic response to both IL-1, and TNF-,, indicating that nitric oxide is probably not involved. In contrast, the Na+/K+ ATPase inhibitor ouabain prevents the IL-1,- and TNF-,-stimulated 2-deoxyglucose (2DG) uptake. When treatment of astrocytes with a cytokine was followed 24 h later by an acute application of glutamate, a synergistic enhancement in glucose utilization was observed. This effect was greatly reduced by ouabain. These data suggest that Na+ pump activity is a common target for both the long-term metabolic action of cytokines promoted by the activation of distinct signaling pathways and the enhanced metabolic response to glutamate. GLIA 39:10,18, 2002. © 2002 Wiley-Liss, Inc. [source] Estrogen and non-genomic upregulation of voltage-gated Na+ channel activity in MDA-MB-231 human breast cancer cells: Role in adhesion,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010Scott P. Fraser External (but not internal) application of ,-estradiol (E2) increased the current amplitude of voltage-gated Na+ channels (VGSCs) in MDA-MB-231 human breast cancer (BCa) cells. The G-protein activator GTP-,-S, by itself, also increased the VGSC current whilst the G-protein inhibitor GDP-,-S decreased the effect of E2. Expression of GPR30 (a G-protein-coupled estrogen receptor) in MDA-MB-231 cells was confirmed by PCR, Western blot and immunocytochemistry. Importantly, G-1, a specific agonist for GPR30, also increased the VGSC current amplitude in a dose-dependent manner. Transfection and siRNA-silencing of GPR30 expression resulted in corresponding changes in GPR30 protein expression but only internally, and the response to E2 was not affected. The protein kinase A inhibitor, PKI, abolished the effect of E2, whilst forskolin, an adenylate cyclase activator, by itself, increased VGSC activity. On the other hand, pre-incubation of the MDA-MB-231 cells with brefeldin A (a trans -Golgi protein trafficking inhibitor) had no effect on the E2-induced increase in VGSC amplitude, indicating that such trafficking (,externalisation') of VGSC was not involved. Finally, acute application of E2 decreased cell adhesion whilst the specific VGSC blocker tetrodotoxin increased it. Co-application of E2 and tetrodotoxin inhibited the effect of E2 on cell adhesion, suggesting that the effect of E2 was mainly through VGSC activity. Pre-treatment of the cells with PKI abolished the effect of E2 on adhesion, consistent with the proposed role of PKA. Potential implications of the E2-induced non-genomic upregulation of VGSC activity for BCa progression are discussed. J. Cell. Physiol. 224: 527,539, 2010. © 2010 Wiley-Liss, Inc. [source] The acute effects of smokeless tobacco (snuff) on gingival blood flow in manJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2001Antonios Mavropoulos Snuff-induced blood flow responses in the gingiva were evaluated in 22 healthy casual consumers of tobacco. Laser Doppler flowmetry (LDF) was used to measure blood flow simultaneously and continuously on two gingival sites (buccal aspect of the papillae between the upper lateral incisors and canines). In addition, measurements of skin blood flow in the forehead and palmar side of the left thumb were performed. Arterial blood pressure (BP) and heart rate (HR) were also recorded. Unilateral application of commercial snuff (500 mg, 1%) caused a marked and rapid increase in gingival blood flow (GBF) on the exposed side (p<0.001). Blood flow increased also in the contralateral gingiva and forehead skin (p<0.05). Skin blood flow in the thumb showed an insignificant decrease. BP and HR increased. Vascular conductance increased significantly in the snuff-exposed gingiva but not in the contralateral gingiva or the forehead. Vascular conductance was largely unaffected in the thumb. It is concluded that acute application of snuff, besides giving rise to typical changes in BP and HR, increases GBF in and around the exposed area, probably through activation of sensory nerves and the subsequent release of vasodilatory peptides from their peripheral endings. Blood flow in unexposed gingival and forehead skin may increase probably due to humoral or nervously mediated mechanisms. However, a passive pressure-induced hyperaemia in the unexposed gingiva and forehead skin can not be excluded. [source] Lactobacillus reuteri ingestion and IKCa channel blockade have similar effects on rat colon motility and myenteric neuronesNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2010B. Wang Abstract, Background, We have previously shown that ingestion of Lactobacillus reuteri may modulate colonic enteric neuron activity but with unknown effects on colon motility. The aim of the present report was to elucidate the neuronal mechanisms of action of the probiotic by comparing the effects on motility of L. reuteri ingestion with blockade of a specific ionic current in enteric neurons. Methods, We have used intraluminal pressure recordings from ex vivo rat colon segments and whole cell patch clamp recordings from neurons of rat longitudinal muscle myenteric plexus preparations to investigate the effects of L. reuteri and TRAM-34 on colon motility and neurophysiology. The effects of daily feeding of 109L. reuteri bacteria or acute application of TRAM-34 on threshold fluid filling pressure or pulse pressure was measured. Key Results,Lactobacillus reuteri increased intraluminal fluid filling pressure thresholds for evoking pressure pulses by 51% from 0.47 ± 0.17 hPa; the probiotic also decreased the pulse pressure amplitudes, but not frequency, by 18% from 3.91 ± 0.52 hPa. The intermediate conductance calcium-dependent potassium (IKCa) channel blocker TRAM-34 (3 ,mol L,1) increased filling threshold pressure by 43% from 0.52 ± 0.22 hPa and reduced pulse pressure amplitude by 40% from 2.63 ± 1.11 hPa; contraction frequency was unaltered. TRAM-34 (3 ,mol L,1) reduced membrane polarization, leak conductance and the slow afterhyperpolarization current in 16/16 myenteric rat colon AH cells but 19/19 S cells were unaffected. Conclusions & Inferences, The present results are consistent with L. reuteri enhancing tonic inhibition of colon contractile activity by acting via the IKCa channel current in AH cells. [source] Neuropeptide Y delays hippocampal kindling in the ratHIPPOCAMPUS, Issue 5 2003Sophie Reibel Abstract Chronic intrahippocampal infusion of the neurotrophin brain-derived neurotrophic factor (BDNF) has been shown to delay kindling epileptogenesis in the rat and several lines of evidence suggest that neuropeptide Y could mediate these inhibitory effects. Chronic infusion of BDNF leads to a sustained overexpression of neuropeptide Y in the hippocampus, which follows a time course similar to that of the suppressive effects of BDNF on kindling. In vivo, acute applications of neuropeptide Y or agonists of its receptors exert anticonvulsant properties, especially on seizures of hippocampal origin. In this study, we examined how chronic infusion of this neuropeptide in the hippocampus affected kindling epileptogenesis. A 7-day continuous infusion of neuropeptide Y in the hippocampus delayed the progression of hippocampal kindling in the rat, whereas anti-neuropeptide Y immunoglobulins had an aggravating effect. These results show that neuropeptide Y exerts anti-epileptogenic properties on seizures originating within the hippocampus and lend support to the hypothesis that BDNF delays kindling at least in part through upregulation of this neuropeptide. They also suggest that the seizure-induced upregulation of neuropeptide Y constitutes an endogenous mechanism counteracting excessive hippocampal excitability. Hippocampus 2003;13:557,560. © 2003 Wiley-Liss, Inc. [source] | |||||||||||||