1.Study on the interactions between Ligusticum chuanxiong extract and cardiac muscle membrane receptors by CMSP chromatography.
Xuan-feng YUE ; Yan-ni ZHANG ; Zhi-qi ZHANG ; Zhen-jun TIAN ; Jian-xiong YANG ; Fa-rong LI
China Journal of Chinese Materia Medica 2005;30(2):129-133
OBJECTIVETo study the interactions between Ligusticum chuanxiong Hort extract and cardiac muscle membrane receptors.
METHODThe cell membrane of rabbit cardiac muscle was fixed on silicon to make cell membrane stationary phase (CMSP), and then the interactions were studied by comparing the retention characteristics of the extracts from different solvents with those of the antagonists or activators corresponding to known receptors in cardiac muscle membrane, and by competition effect on the retention characteristics of extracts when adding the antagonists or activators into the mobile phase.
RESULTWater extract and ethanol extract both had retentions on CMSP; the retention characteristics of water extract could be affected when water extract was in competition with the antagonists for alpha receptor, and could not be affected when with the activator beta1 receptor.
CONCLUSIONIt is possible that some components in water extract may combine with alpha receptor and no component with beta1 receptor, and that some components in ethanol extract may combine with cardiac muscle cell membrane. The process between active components and receptors in vivo can be imitated through the interactions between drugs and CMSP. The method provides references for the resolution of two applications: to screen the active components from Chinese medicine, and to figure out the type of receptors involved.
Adrenergic alpha-Agonists ; metabolism ; Adrenergic alpha-Antagonists ; metabolism ; Adrenergic beta-Agonists ; metabolism ; Adrenergic beta-Antagonists ; metabolism ; Animals ; Cell Membrane ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Ligusticum ; chemistry ; Male ; Myocytes, Cardiac ; cytology ; metabolism ; Plants, Medicinal ; chemistry ; Protein Binding ; Rabbits ; Receptors, Adrenergic, alpha ; metabolism ; Receptors, Adrenergic, beta ; metabolism
2.Pathogenesis and Individualized Treatment for Postural Tachycardia Syndrome in Children.
Wen-Rui XU ; Hong-Fang JIN ; Jun-Bao DU
Chinese Medical Journal 2016;129(18):2241-2245
OBJECTIVEPostural tachycardia syndrome (POTS) is one of the major causes of orthostatic intolerance in children. We systematically reviewed the pathogenesis and the progress of individualized treatment for POTS in children.
DATA SOURCESThe data analyzed in this review are mainly from articles included in PubMed and EMBASE.
STUDY SELECTIONThe original articles and critical reviews about POTS were selected for this review.
RESULTSStudies have shown that POTS might be related to several factors including hypovolemia, high catecholamine status, abnormal local vascular tension, and decreased skeletal muscle pump activity. In addition to exercise training, the first-line treatments mainly include oral rehydration salts, beta-adrenoreceptor blockers, and alpha-adrenoreceptor agonists. However, reports about the effectiveness of various treatments are diverse. By analyzing the patient's physiological indexes and biomarkers before the treatment, the efficacy of medication could be well predicted.
CONCLUSIONSThe pathogenesis of POTS is multifactorial, including hypovolemia, abnormal catecholamine state, and vascular dysfunction. Biomarker-directed individualized treatment is an important strategy for the management of POTS children.
Adrenergic alpha-Agonists ; therapeutic use ; Adrenergic beta-Antagonists ; therapeutic use ; Catecholamines ; metabolism ; Humans ; Postural Orthostatic Tachycardia Syndrome ; drug therapy ; metabolism ; pathology ; therapy
3.Common approach to managing lower urinary tract symptoms and erectile dysfunction.
Jennifer M TAYLOR ; Rowena DESOUZA ; Run WANG
Asian Journal of Andrology 2008;10(1):45-53
The present paper serves as a review of the associations between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), with a focus on common and combined pathways for treatment. LUTS and ED are common conditions seen in general urologic practice. Research has started to establish epidemiologic and pathophysiologic links between the two conditions and a strong association confirmed across multiple studies. Men seeking care for one condition should always be interviewed for complaints of the other condition. Proposed common pathways include alpha-1 adrenergic receptor imbalance, Rho-kinase overactivity, endothelial cell dysfunction and atherosclerosis-induced ischemia. Medical therapy has replaced surgery as the first-line treatment for LUTS in most patients, with the incorporation of alpha-adrenergic receptor antagonists (alpha-ARAs) and 5-alpha-reductase inhibitors (5-ARIs) into everyday practice. Treatment with alpha-ARAs contributes to some improvement in ED, whereas use of 5-ARIs results in worsened sexual function in some patients. Phosphodiesterase-5 (PDE-5) inhibitors have revolutionized the treatment of ED with a simple oral regimen, and new insights demonstrate a benefit of combined use of PDE-5 inhibitors and alpha-ARAs. The mechanisms of action of these medications support these observed benefits, and they are being studied in the basic science and clinical settings. In addition, novel mechanisms for therapy have been proposed based on clinical and research observations. The minimally invasive and surgical treatments for LUTS are known to have adverse effects on ejaculatory function, while their effects on erectile function are still debated. Much remains to be investigated, but it is clear that the associations between LUTS and ED lay the foundation for future therapies and possible preventative strategies.
5-alpha Reductase Inhibitors
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Adrenergic alpha-Antagonists
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therapeutic use
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Atherosclerosis
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complications
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Endothelium, Vascular
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Erectile Dysfunction
;
etiology
;
therapy
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Humans
;
Male
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Phosphodiesterase Inhibitors
;
therapeutic use
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Prostatic Hyperplasia
;
complications
;
surgery
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Receptors, Adrenergic, alpha
;
physiology
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Urologic Diseases
;
etiology
;
therapy
;
rho-Associated Kinases
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metabolism
4.Synthesis and anti alpha-adrenoceptor activity in vitro of 4-((4-((2-substitutedphenoxy)ethyl)-1-piperazinyl) methyl)- 1,2-dihydro-quinoline-2-one compounds.
Hui LIU ; Chong-zhao RAN ; Lin XIA ; Pei-zhou NI
Acta Pharmaceutica Sinica 2002;37(3):181-185
AIMTo study the synthesis and anti alpha-adrenoceptor activity of 1,2-dihydro-quinoline-2-one compounds.
METHODSAcylation, bromination and cyclization, and substitute reactions were used in the synthesis of the title compounds IV. A proposed mechanism was showed to explain the unusual compounds 5 and 6 in the route C. The inhibition activity of the six target compounds were tested.
RESULTSTwelve new compounds were synthesized (II1-6 and IV1-6). Among them, six new compounds (IV1-6) are the title compounds. Structure of the title compounds were determined by IR, 1HNMR, MS and HRMS.
CONCLUSIONCompounds IV3, IV4 and IV6 showed inhibitiion activity, and were worth further studying.
Adrenergic alpha-Antagonists ; chemical synthesis ; pharmacology ; Animals ; Aorta ; drug effects ; In Vitro Techniques ; Molecular Structure ; Phenethylamines ; chemical synthesis ; pharmacology ; Quinolones ; chemical synthesis ; pharmacology ; Rabbits ; Receptors, Adrenergic, alpha ; drug effects ; metabolism ; Technology, Pharmaceutical
5.Spinal Gabapentin and Antinociception: Mechanisms of Action.
Myung Ha YOON ; Jeong Il CHOI ; Seong Wook JEONG
Journal of Korean Medical Science 2003;18(2):255-261
Spinal gabapentin has been known to show the antinociceptive effect. Although several assumptions have been suggested, mechanisms of action of gabapentin have not been clearly established. The present study was undertaken to examine the action mechanisms of gabapentin at the spinal level. Male SD rats were prepared for intrathecal catheterization. The effect of gabapentin was assessed in the formalin test. After pretreatment with many classes of drugs, changes of effect of gabapentin were examined. General behaviors were also observed. Intrathecal gabapentin produced a suppression of the phase 2 flinching, but not phase 1 in the formalin test. The antinociceptive action of intrathecal gabapentin was reversed by intrathecal NMDA, AMPA, D-serine, CGS 15943, atropine, and naloxone. No antagonism was seen following administration of bicuculline, saclofen, prazosin, yohimbine, mecamylamine, L-leucine, dihydroergocristine, or thapsigargin. Taken together, intrathecal gabapentin attenuated only the facilitated state. At the spinal level, NMDA receptor, AMPA receptor, nonstrychnine site of NMDA receptor, adenosine receptor, muscarinic receptor, and opioid receptor may be involved in the antinociception of gabapentin, but GABA receptor, L-amino acid transporter, adrenergic receptor, nicotinic receptor, serotonin receptor, or calcium may not be involved.
Acetic Acids/administration & dosage
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Acetic Acids/metabolism
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Acetic Acids/pharmacology*
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Adrenergic Antagonists/metabolism
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Adrenergic alpha-Antagonists/metabolism
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Analgesics/administration & dosage
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Analgesics/metabolism
;
Analgesics/pharmacology*
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Animals
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Atropine/metabolism
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Dihydroergocristine/metabolism
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Enzyme Inhibitors/metabolism
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Excitatory Amino Acid Agonists/metabolism
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GABA Antagonists/metabolism
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Injections, Spinal
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Leucine/metabolism
;
Male
;
Mecamylamine/metabolism
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Muscarinic Antagonists/metabolism
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N-Methylaspartate/metabolism
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Naloxone/metabolism
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Narcotic Antagonists/metabolism
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Nicotinic Antagonists/metabolism
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Pain Measurement
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Quinazolines/metabolism
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Rats
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Rats, Sprague-Dawley
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Serine/metabolism
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Spinal Cord/drug effects*
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Thapsigargin/metabolism
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Triazoles/metabolism
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism
6.5-HT1A/1B receptors, alpha2-adrenoceptors and the post-receptor adenylate cyclase activation in the mice brain are involved in the antidepressant-like action of agmatine.
Xian-Zhong JIANG ; Yun-Feng LI ; You-Zhi ZHANG ; Hong-Xia CHEN ; Ji LI ; Nai-Ping WANG
Acta Pharmaceutica Sinica 2008;43(5):467-473
This study is to explore the possible mechanisms of the antidepressant-like effect of agmatine. By using two traditional "behavior despair" model, tail suspension test and forced swimming test, we examined the effects of some monoamine receptor antagonists (including beta-adrenergic receptor antagonist propranolol, beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol, alpha2-adrenergic receptor antagonists yohimbine and idazoxan and 5-HT3 receptor antagonist tropisetron) on the antidepressant-like action of agmatine in mice. Activity of adenylate cyclase (AC) in the synapse membrane from rat frontal cortex was determined by radioimmunoassay. Single dose of agmatine (5-40 mg x kg(-1), ig) dose-dependently decrease the immobility time in tail suspension test in mice, indicating an antidepressant-like effect. The effect of agmatine (40 mg x kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg x kg(-1), ip), alpha2-adrenergic receptor antagonists yohimbine (5-10 mg x kg(-1), ip) or idazoxan (4 mg x kg(-1), ip), but not beta-adrenergic receptor antagonist propranolol (5-20 mg x kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5-40 mg x kg(-1), ip). Agmatine (5-40 mg x kg(-1), ig) also dose-dependently decrease the immobility time in forced swimming test in mice. The effect of agmatine (40 mg x kg(-1), ig) was also antagonized by pindolol (20 mg x kg(-1), ip), yohimbine (5-10 mg x kg(-1), ip), or idazoxan (4 mg x kg(-1), ip). Incubation of agmatine (0.1-6.4 micromol x L(-1)) with the synaptic membrane extracted from rat frontal cortex activated the AC in a dose-dependent manner in vitro. While the effect of agmatine (6.4 micromol x L(-1)) was dose-dependently antagonized by pindolol (1 micromol x L(-1)) or yohimbine (0.25-1 micromol x L(-1)). Chronic treatment with agmatine (10 mg x kg(-1), ig, bid, 2 w) or fluoxetine (10 mg x kg(-1), ig, bid, 2 w) increased the basic activity, as well as the Gpp (NH)p (1-100 micromol x L(-1)) stimulated AC activity in rat prefrontal cortex. These results indicate that regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action.
Adenylyl Cyclases
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metabolism
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Adrenergic alpha-Antagonists
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pharmacology
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Adrenergic beta-Antagonists
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pharmacology
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Agmatine
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administration & dosage
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pharmacology
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Animals
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Antidepressive Agents
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administration & dosage
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pharmacology
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Behavior, Animal
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drug effects
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Depression
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metabolism
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physiopathology
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Dose-Response Relationship, Drug
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Fenclonine
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pharmacology
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Idazoxan
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pharmacology
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Male
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Mice
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Pindolol
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pharmacology
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Random Allocation
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Rats
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Rats, Wistar
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Receptors, Biogenic Amine
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antagonists & inhibitors
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Serotonin 5-HT1 Receptor Antagonists
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Swimming
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Synapses
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enzymology
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Yohimbine
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pharmacology
7.Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats.
Ying LIN ; Xi ZHU ; Wan-Zhen YAO ; Yan-Lin YANG ; La-Ta A ; Li CHEN
Chinese Medical Journal 2011;124(7):1069-1074
BACKGROUNDAlpha 2A adrenergic receptor (AR) is a subtype of α2 AR belonging to G protein-coupled receptors, and exerts a variety of biological effects. Recent studies have demonstrated that the α2A AR activation was closely related with inflammatory reaction. The present study aimed to investigate the influence of α2A AR antagonist, yohimbine, on the severity of endotoxin-induced acute lung injury in rats.
METHODSA total of 72 male Sprague-Dawley rats were randomly divided into three groups: control group, lipopolysaccharide (LPS) group and LPS + yohimbine group. Rats were intratracheally administrated with normal saline or LPS (300 µg), and the rats in the LPS + yohimbine group were treated with additional yohimbine (2 mg/kg, i.p) soon after LPS administration. Six, 24 and 48 hours after treatment, arterial blood gas analysis was carried out, and optical microscopy was performed to evaluate pathological changes in the lung, and lung injury score was assessed. The count of white blood cells in bronchoalveolar lavage fluid (BALF) was determined. The levels of norepinephrine, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in BALF were measured with enzyme-linked immunosorbent assay. Immunocytochemistry was performed for the detection of α2A AR on inflammatory cells in BALF.
RESULTSWhen compared with the control group, the oxygenation index in the LPS group was significantly decreased, and white blood cell count, the lung histopathological scores, levels of norepinephrine and IL-6 as well as α2A AR expression on inflammatory cells in the BALF were dramatically increased at different time points, and the concentrations of TNF-α and IL-1β were also increased except at 48 hours after LPS administration. The oxygenation index decreased while white blood cell count in BALF and the lung histopathological scores were obviously increased in the LPS + yohimbine group. The level of norepinephrine in BALF was increased at each time interval in the LPS + yohimbine group, and so did the levels of TNF-α, IL-1β and IL-6 at 6 and 48 hours after LPS administration respectively. When compared with the LPS group, the oxygenation index, white blood cell count, the lung histopathological scores and the level of IL-6 in the LPS + yohimbine group were significantly improved at each time interval, and the concentrations of TNF-α and IL-1β were also lower at 24 hours of LPS administration (all P < 0.05). Correlation analysis indicated the level of norepinephrine was related to the levels of TNF-α, IL-1β and IL-6 in the BALF and the lung histopathological scores (r = 0.703, r = 0.595, r = 0.487 and r = 0.688, respectively, P < 0.001) and the intensity scores of immunoreactivity to α2A AR on inflammatory cells were also associated with the levels of TNF-α, IL-1β and IL-6 as well as the lung histopathologial scores (r = 0.803, r = 0.978, r = 0.716 and r = 0.808, respectively, P < 0.001).
CONCLUSIONSYohimbine can inhibit TNF-α, IL-1β and IL-6 overproduction and relieve the severity of pulmonary inflammation induced by endotoxin, which is maybe mediated by blockade of α2A AR on inflammatory cells.
Acute Lung Injury ; chemically induced ; drug therapy ; Adrenergic alpha-2 Receptor Antagonists ; therapeutic use ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Enzyme-Linked Immunosorbent Assay ; Immunohistochemistry ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; toxicity ; Male ; Norepinephrine ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-2 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Yohimbine ; therapeutic use
8.Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress and inflammatory response in Kupffer cells.
Jinmei SHEN ; Li LI ; Lili JIANG ; Gan FU
Journal of Central South University(Medical Sciences) 2016;41(5):477-481
OBJECTIVE:
To evaluate whether dexmedetomidine hydrochloride, an α(2)-adrenergic receptor agonist, can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells.
METHODS:
H(2)O(2)-induced oxidative damage model of Kupffer cell was established. Kupffer cells were pre-conditioned by dexmedetomidine hydrochloride or Yohimbine for 24 h. MTT colorimetry was used to demonstrate the survival rate of Kupffer cells. The levels of lactate dehydrogenase (LDH), malonaldehyde (MDA) and TNF-α in the culture medium were assessed by corresponding kits.
RESULTS:
Dexmedetomidine hydrochloride protected Kupffer cells from H(2)O(2)-induced oxidative damage, showing an increase in the cell survival rate while a decrease in LDH, MDA and TNF-α release in the culture supernatant. Yohimbine, an α(2)-adrenergic receptor antagonist, completely neutralized the protective effect of Dexmedetomidine hydrochloride on Kupffer cells. Yohimbine itself had no effect on H(2)O(2)-induced oxidative damage and inflammatory response.
CONCLUSION
Dexmedetomidine hydrochloride can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells through activation of α(2)-adrenergic receptors.
Adrenergic alpha-2 Receptor Antagonists
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pharmacology
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Cell Survival
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Cells, Cultured
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Dexmedetomidine
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pharmacology
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Humans
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Hydrogen Peroxide
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pharmacology
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Kupffer Cells
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cytology
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drug effects
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L-Lactate Dehydrogenase
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metabolism
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Malondialdehyde
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metabolism
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Oxidative Stress
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drug effects
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Receptors, Adrenergic, alpha-2
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metabolism
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Tumor Necrosis Factor-alpha
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metabolism
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Yohimbine
;
pharmacology
9.Alpha-adrenoceptor antagonism by Crassostrea gigas oyster extract inhibits noradrenaline-induced vascular contraction in Wistar rats.
Kylie CONNOLLY ; Douglas JACKSON ; Candice PULLEN ; Andrew FENNING
Journal of Integrative Medicine 2015;13(3):194-200
OBJECTIVECrassostrea gigas oyster extract has been reported to have antioxidant, antihypertensive and lipid-lowering properties that may be useful for treating cardiovascular diseases. This study aimed to evaluate the effect of C. gigas oyster extract on cardiovascular function in tissues from healthy rats.
METHODSSingle-cell microelectrode and isolated thoracic aortic organ bath studies were performed on tissues from 8-week-old healthy Wistar rats, using varying concentrations of C. gigas oyster extract. To elucidate a mechanism of action for the oyster's vasoactive properties, concentration response curves were carried out in the presence of a calcium channel inhibitior (verapamil), a nitric oxide synthase inhibitor (N(G)-nitro-L-arginine methyl ester), a potassium channel inhibitor (4-aminopyridine), in addition to the α-adrenoceptor inhibitor prazosin.
RESULTSOyster solution at 7 500 mg/mL inhibited noradrenaline-induced contraction in isolated aortic rings. Cardiac electrophysiology results showed that neither concentration of oyster solution was able to significantly reduce action potential duration at all phases of repolarisation in left ventricular papillary muscles from healthy animals.
CONCLUSIONWhen administered to healthy vascular tissue, C. gigas oyster extract inhibits contraction induced by noradrenaline. This effect is likely to be mediated through α-adrenoceptor inhibition, and to a lesser extent, calcium modulating activity.
Action Potentials ; drug effects ; Adrenergic alpha-Antagonists ; pharmacology ; Animals ; Aorta, Thoracic ; drug effects ; physiology ; Calcium ; metabolism ; Crassostrea ; Heart ; drug effects ; physiology ; Male ; Norepinephrine ; antagonists & inhibitors ; pharmacology ; Rats ; Rats, Wistar ; Vasoconstriction ; drug effects
10.Effects of carvedilol on cardiomyocyte apoptosis and gene expression in vivo after ischemia-reperfusion in rats.
Hesong ZENG ; Xiaochun LIU ; Huayue ZHAO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2003;23(2):127-130
The effects of carvedilol on cardiomyocyte apoptosis and expression of bcl-2, bax genes following ischemia (0.5 h) and reperfusion (48 h) in vivo and the possible biological mechanism of carvedilol inhibiting cardiomyocyte apoptosis were studied. The left anterior descending artery in Wistar rats were ligated to establish ischemia-reperfusion (I/R) models. The model animals were divided into two groups: I/R group, the model rats not subject to other treatments except ischemia-reperfusion (n = 8); carvedilol-treated group (n = 8), I/R model rats treated with carvedilol. Eight rats in the sham-operated group were subjected to only experimental open operation. The number of apoptotic cardiomyocyte was determined by TUNEL staining. Immunohistochemistry and in situ hybridization histochemistry (ISHH) were used to detect the expression of bcl-2 and bax genes. Image processing system was used to quantitatively dispose the positive metric substances of both immunohistochemistry and ISHH through the average optical density (OD) value. The results showed that the number of the apoptotic cells were 36.18 +/- 9 (I/R group), 0-1 (sham-operated group) and 9.5 +/- 3 (carvedilol-treated group) in each visual field respectively with the difference being very significant among the groups (P < 0.001). The OD values of bcl-2 protein in sham-operated group, I/R group and carvedilol-treated group were 0.14 +/- 0.01, 0.08 +/- 0.02 and 0.15 +/- 0.03, respectively. The OD values of bcl-2 mRNA in sham-operated group, I/R group and carvedilol-treated group were 0.08 +/- 0.01, 0.06 +/- 0.01 and 0.09 +/- 0.01, respectively. There was no significant difference between carvedilol-treated group and I/R group (P > 0.05). The OD values of bax protein in I/R group, sham-operated and carvedilol-treated-treated group were 0.13 +/- 0.02, 0.07 +/- 0.01, 0.06 +/- 0.01, respectively. There was very significant difference between carvedilol-treated group and I/R group (P < 0.01). Bcl-2/bax ratio was 1.07 +/- 0.14 (I/R group), 1.28 +/- 0.16 (sham-operated group), 2.5 +/- 0.26 (carvedilol-treated group) respectively with the difference being very significant between carvedilol-treated group and I/R group (P < 0.05). It was indicated that carvedilol could inhibit cardiomyocyte apoptosis following ischemia and reperfusion, which was related to the increased bcl-2/bax ratio due to inhibition of bax gene expression.
Adrenergic alpha-Antagonists
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pharmacology
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Adrenergic beta-Antagonists
;
pharmacology
;
Animals
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Apoptosis
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drug effects
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Carbazoles
;
pharmacology
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Gene Expression
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Myocardial Ischemia
;
genetics
;
pathology
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Myocardial Reperfusion Injury
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genetics
;
pathology
;
Myocytes, Cardiac
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pathology
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Propanolamines
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pharmacology
;
Proto-Oncogene Proteins
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metabolism
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Proto-Oncogene Proteins c-bcl-2
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metabolism
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Random Allocation
;
Rats
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Rats, Wistar
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bcl-2-Associated X Protein