1.Inhibitory Effect of CCK-8 on Methamphetamine-Induced Apoptosis.
Wu-Hua ZHANG ; Ming-Long ZHANG ; Wei-Wei JING ; Bing XIE ; Hai-Tao BI ; Feng YU ; Bin CONG ; Chun-Ling MA ; Di WEN
Journal of Forensic Medicine 2021;37(6):796-805
OBJECTIVES:
To investigate the inhibitory effect of cholecystokinin octapeptide (CCK-8) binding to cholecystokinin 2 receptor (CCK2R) on methamphetamine (METH)-induced neuronal apoptosis, and to explore the signal transduction mechanism of β-arrestin 2 in CCK-8 inhibiting METH-induced neuronal apoptosis.
METHODS:
SH-SY5Y cell line was cultured, and HEK293-CCK1R and HEK293-CCK2R cell line were constructed by lentivirus transfection. Small interfering RNA (siRNA) was used to knockdown the expression of β-arrestin 2. Annexin Ⅴ-FITC/PI staining and flow cytometry were used to detect the apoptotic rate of cells, and Western blotting was used to detect the expression of apoptosis-related proteins.
RESULTS:
The apoptosis of SH-SY5Y cells was induced by 1 mmol/L and 2 mmol/L METH treatment, the number of nuclear fragmentation and pyknotic cells was significantly increased, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were increased. CCK-8 pre-treatment at the dose of 0.1 mmol/L and 1 mmol/L significantly reversed METH-induced apoptosis in SH-SY5Y cells, and inhibited cell nuclear fragmentation, pyknosis and the changes of apoptosis-related proteins induced by METH. In lentivirus transfected HEK293-CCK1R and HEK293-CCK2R cells, the results revealed that CCK-8 had no significant effect on METH-induced changes of apoptosis-related proteins in HEK293-CCK1R cells, but it could inhibit the expression level of apoptosis-related proteins in HEK293-CCK2R cells induced by METH. The inhibitory effect of CCK-8 on METH-induced apoptosis was blocked by the knockdown of β-arrestin 2 expression in SH-SY5Y cells.
CONCLUSIONS
CCK-8 can bind to CCK2R and exert an inhibitory effect on METH-induced apoptosis by activating the β-arrestin 2 signal.
Apoptosis/physiology*
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Central Nervous System Stimulants/pharmacology*
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HEK293 Cells
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Humans
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Methamphetamine/pharmacology*
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Sincalide/pharmacology*
2.Regulatory effect of caffeine on the acute and the chronic pain and its possible mechanisms.
Yu-Guan ZHANG ; Le SHEN ; Li XU ; Yu-Guang HUANG
Acta Academiae Medicinae Sinicae 2014;36(6):697-700
Caffeine,as an important component of refreshment beverage,has been used for a long history. In recent years,its effect on pain relief has been widely explored. As one of nonselective adenosine receptor blockers,caffeine plays different roles in the central and peripheral pain. This review explores the roles of caffeine in acute and chronic pain and the potential mechanisms.
Adenosine
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antagonists & inhibitors
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metabolism
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Caffeine
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pharmacology
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therapeutic use
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Central Nervous System Stimulants
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pharmacology
;
therapeutic use
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Chronic Pain
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drug therapy
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Humans
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Pain
;
drug therapy
3.Pharmacokinetics--pharmacodynamics of modafinil in mice.
Zhang-Qing MA ; Zong-Yuan HONG ; Wu-San WANG ; Fang TAO
Acta Pharmaceutica Sinica 2012;47(1):101-104
To guide the reasonable clinical application of modafinil (MOD), pharmacokinetics and pharmacodynamics of MOD in mice and the correlation between them were investigated. Male mice (Kunming strain) were given a single oral dose of MOD (120 mg x kg(-1)). The plasma concentration of MOD was measured by HPLC and the pharmacokinetic parameters were calculated with DAS 3.0 software. For another batch of male Kunming strain mice, their locomotor activities were recorded by an infrared ray passive sensor after a same oral dose of MOD, and the synchronization and correlation between the changes of MOD plasma concentration and the locomotor activity induced by MOD were compared and analyzed. The results showed that the plasma concentration-time curve of MOD was fitted to two-compartment open model with a first order absorption. The main pharmacokinetic parameters t1/2alpha, t1/2beta, t(max), C(max) and AUC(0-inifinity) were 0.42 h, 3.10 h, 1.00 h, 41.34 mg x L(-1) and 142.22 mg x L(-1) x h, respectively. MOD significantly increased locomotor activity and the effect lasted for about 4 h. The changes of MOD plasma concentration and the locomotor activity induced by MOD were synchronous. In conclusion, there is a significant correlation between the effect of MOD and its plasma concentration after administration of 120 mg x kg(-1) in mice.
Administration, Oral
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Animals
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Area Under Curve
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Benzhydryl Compounds
;
administration & dosage
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blood
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pharmacokinetics
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pharmacology
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Central Nervous System Stimulants
;
administration & dosage
;
blood
;
pharmacokinetics
;
pharmacology
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Chromatography, High Pressure Liquid
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Dose-Response Relationship, Drug
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Male
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Mice
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Motor Activity
;
drug effects
4.GABA A receptor participates in respiratory enhancement induced by nikethamide in neonatal rats.
Zhi-bin QIAN ; Ying QI ; Zhong-hai WU
Journal of Southern Medical University 2008;28(3):301-304
OBJECTIVETo investigate the role of GABA A receptor in nikethamide-induced respiratory enhancement in the medullary slices of neonatal rats.
METHODSEx vivo medullary slices of neonatal rats (1 to 3 days old) containing the medial region of the nucleus retrofacialis with the hypoglossal nerve rootlets were prepared and perfused with modified Kreb's solution to record respiration-related rhythmic discharge activity (RRDA) from the hypoglossal nerve rootlets using suction electrodes. Thirty RRDA-positive slices were randomized into 5 equal groups and perfused with nikethamide (at concentrations of 0.5, 1, 3, 5, 7, and 10 microg/ml with the optimal nikethamide concentration determined), GABA (at 10, 20, 40, and 60 micromol/ to determine the optimal concentration), 10 micromol/ bicuculline, 10 micromol/ bicuculline plus 40 micromol/L GABA, and 5 microg/ml nikethamide followed by 5 microg/ml nikethamide plus 10 micromol/ bicuculline after wash out, respectively.
RESULTSNikethamide increased RRDA at the concentrations of 0.5-7 microg/ml, and 5 microg/ml nikethamide showed the most distinct effect on the inspiratory time (TI), integral amplitude (IA), and respiratory cycle (RC). GABA at 40 micromol/ showed the most effective inhibition of RRDA in terms of TI, IA, and RC. Bicuculline at 10 micromol/ could increase the IA, TI and RC, but the combination of 10 micromol/ bicuculline and 40 micromol/ GABA had no significant effects on RRDA. Compared with nikethamide used alone, nikethamide plus bicuculline significantly increased TI and IA without affecting RC.
CONCLUSIONNikethamide can enhance RRDA of the hypoglossal nerve rootlets in the medullary slices of neonatal rats, and the effect can be partially mediated by the GABA A receptor.
Animals ; Animals, Newborn ; Central Nervous System Stimulants ; pharmacology ; Female ; In Vitro Techniques ; Male ; Medulla Oblongata ; physiology ; Nikethamide ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; physiology ; Respiration ; drug effects ; Respiratory Center ; drug effects ; physiology
5.Mechanism of hypothalamic effect in small intestine electro-activity of rats regulated by fructus aurantii immaturus.
Ting-ting SONG ; Qing-ying XUN ; Yi-quan WEI
Chinese Journal of Integrated Traditional and Western Medicine 2006;26 Suppl():55-58
OBJECTIVETo observe the effect of Fructus Aurantii Immaturus (FAI) on the electro-activity of small intestines in rats, and evaluate the interrelations between the FAI regulating effect and choecystokinin (CCK) and somatostatin (SS).
METHODSMigrating myoelectric complex (MMC) cyclic period, the ratio of the active time to the cyclic period, and the number of the fast wave within the active time per minute were observed between FAI and the normal saline group by external alimentary canal electrodes; the CCK contents in dorsomedial hypothalamic nucleus (DMH), ventromedia hypothalamic nucleus (VMH), lateral hypothalamus area (LHA) and SS in VMH, LHA, paraventricular nucleus (PVN) by using immuno-chemistry technique and micro-image pattern quantitative analysis and scanning system.
RESULTSThe MMC cyclic period shortened, the ratio of the active time to the cyclic period increased and the number of the fast wave within the active time per minute increased in the FAI group, which showed significant difference from the normal saline group; CCK positive neurons were reduced in the areas of DMH, VMH and LHA, SS positive neurons were increased in the areas of VMH, LHA and PVN in the FAI gioup,which showed significant difference compared with the normal saline and the blank control group.
CONCLUSIONFAI can stimulate the electro-reactivity of small intestines. The stimulative effect of FAI might be related to CCK and SS in hypothamus.
Animals ; Central Nervous System Stimulants ; pharmacology ; Cholecystokinin ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hypothalamus ; drug effects ; metabolism ; Intestine, Small ; drug effects ; physiology ; Myoelectric Complex, Migrating ; drug effects ; Rats ; Somatostatin ; metabolism
6.Changes of Heart Rate Variability during Methylphenidate Treatment in Attention-Deficit Hyperactivity Disorder Children: A 12-Week Prospective Study.
Hayeon Jennifer KIM ; Jaewon YANG ; Moon Soo LEE
Yonsei Medical Journal 2015;56(5):1365-1371
PURPOSE: The aim of this study was to clarify the relationship between the autonomic nervous system and attention deficit hyperactivity disorder (ADHD) rating scales and to evaluate the usefulness of heart rate variability (HRV) as a psychophysiological biomarker for ADHD. MATERIALS AND METHODS: Subjects were recruited from outpatients in the Department of Child and Adolescent Psychiatry at the Korea University Medical Center from August 2007 to December 2010. Subjects received methylphenidate. Time- and frequency-domain analyses of HRV, the Korean ADHD rating scale (K-ARS), and computerized ADHD diagnostic system were evaluated before treatment. After a 12-week period of medication administration, we repeated the HRV measurements and K-ARS rating. RESULTS: Eighty-six subjects were initially enrolled and 37 participants completed the 12-week treatment and HRV measurements subsequent to the treatment. Significant correlations were found between the K-ARS inattention score and some HRV parameters. All of the HRV parameters, except the standard deviations of the normal-to-normal interval, very low frequency, and low frequency to high frequency, showed a significant positive correlation between baseline and endpoint measures in completers. High frequency (HF) and the square root of the mean squared differences of successive normal-to-normal intervals (RMSSD), which are related to parasympathetic vagal tone, showed significant decreases from baseline to endpoint. CONCLUSION: The HRV test was shown to be reproducible. The decrease in HF and RMSSD suggests that parasympathetic dominance in ADHD can be altered by methylphenidate treatment. It also shows the possibility that HRV parameters can be used as psychophysiological markers in the treatment of ADHD.
Adolescent
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Attention/drug effects/*physiology
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Attention Deficit Disorder with Hyperactivity/diagnosis/*drug therapy
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Autonomic Nervous System/physiopathology
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Biomarkers
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Central Nervous System Stimulants/pharmacology/*therapeutic use
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Child
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Female
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Heart Rate/*drug effects/physiology
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Humans
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Male
;
Methylphenidate/pharmacology/*therapeutic use
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Prospective Studies
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Republic of Korea
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Treatment Outcome
7.Methylphenidate increased regional cerebral blood flow in subjects with attention deficit/hyperactivity disorder.
Boong Nyun KIM ; Jae Sung LEE ; Soo Churl CHO ; Dong Soo LEE
Yonsei Medical Journal 2001;42(1):19-29
The regional cerebral blood flow (rCBF) responses to methylphenidate (MPH) treatment were examined in children with attention deficit/hyperactivity disorder (ADHD). Thirty-two male children, diagnosed with ADHD by the DSM-IV diagnostic criteria, other behavioral assessment scales and neuropsychological battery, were studied using 99mTc-HMPAO-single photon emission computed tomography (SPECT). Subjects were studied before and after MPH treatment. First, using an image subtraction method, we obtained a NDR parametric image of each patient and found increased cerebral blood flow in the frontal lobes, caudate nuclei and thalamic areas after treatment. When the changes in SPECT and clinical response were compared, the matching rate, sensitivity and specificity between them were found to be 77.1, 80.0 and 79.2%, respectively. Second, three transaxial brain slices delineating anatomically defined regions of interest (ROI) at 20, 40, and 60mm above the orbitomeatal line (OML) were used, with the average number of counts for each region of interest normalized to the area of the cerebellar maximal uptake. The left and right prefrontal areas, and caudate and thalamic areas showed significant increases in rCBF after MPH treatment. These findings suggested MPH could affect the function of the fronto-striato-thalamic circuit, which is known as the pathophysiologic site of ADHD and could be used to correct the underlying brain dysfunction of ADHD.
Adolescence
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Attention Deficit Disorder with Hyperactivity/radionuclide imaging
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Attention Deficit Disorder with Hyperactivity/physiopathology
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Attention Deficit Disorder with Hyperactivity/drug therapy*
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Central Nervous System Stimulants/pharmacology*
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Cerebrovascular Circulation/drug effects*
;
Child
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Female
;
Human
;
Male
;
Methylphenidate/therapeutic use
;
Methylphenidate/pharmacology*
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Tomography, Emission-Computed, Single-Photon