1.Adult zebrafish as a model organism for assessing the effects of hallucinogenic drugs on behaviors
Hui YAN ; Ruibin SU ; Zehui GONG
Chinese Pharmacological Bulletin 2014;(10):1464-1468
Aims To establish several behavioral paradigms to characterize the psychotropic effects of hallucinogens which ze-brafish was utilized as a model animal, and then to investigate the effects of potent hallucinogenic drugs on these models. Methods With the video record and track system, the behavior was recorded and quantified automatically. In the experiments, the bottom dwelling test, social behavior and mirror test were performed to test the hallucinogenic effects of drugs. Metham-phetamine (METH, 2 mg·L-1) and ketamine (20 mg·L-1) were selected as experimental challenges. The 30 min pre-treat-ment time was chosen based on our prior experience in zebrafish models. Results Compared to the normal group, in dwelling test, acute exposure of zebrafish to METH and ketamine de-creased transitions significantly, and in mirror reflection test, the drug-treated fish changed the preference for mirror zone, and ex-hibited aggressive for their mirror images. The pretreatment of METH and ketamine significantly reduced the contact durations, and the ketamine inhibited the contact frequency each other, the results indicated that the social interaction of zebrafish was im-paired. Conclusion The results confirm high sensitivity of ze-brafish models to hallucinogenic compounds with complex behav-ioral and physiological effects.
2.Effect of agmatine on morphine analgesia and tolerance in a rat model of neuropathic pain
Xiuli WANG ; Ruibin SU ; Hongju YANG
Chinese Journal of Anesthesiology 1996;0(08):-
25% signified analgesic effect. Part II (the effect of agmatine on analgesic effect of morphine). Fifty-six animals with neuropathic pain were randomly divided into 4 groups ( n = 14 each) . Each group received NS or agmatine 20, 40 or 60 mg? kg-1 . 30 min later each group received either NS or morphine 1 mg?kg-1(n=7 each). PWT was measured and PMAP was calculated Part III (the effects of agmatine on the development of morphine tolerance). Morphine tolerance was incuced by morphine 10 mg?kg-1, 3 times a day for 5 days. Thirty-five animals with neuropathic pain were randomly divided into 5 groups ( n = 7 each): group A received NS: group B received NS + morphine; grouop C, D, E received agmatine 5, 10, 20 mg ? kg-1 + morphine 3 times a day for 5 days. PWT was measured on the 5th day and PMAP was calculated. Results PMAP of agmatine (40, 60 mg?kg-1 i.p.) and morphine (1 mg?kg-1 s.c.) were lower than 40% . Agmatine 60 mg?kg-1 increased the PMAP of morphine 1 mg?kg-1 to 84% compared with 34% for morphine alone (P
3.Establishment of a recombinant cell line that stably expresses rat purinergic receptor P2X4 and verification of its function
Linlin LI ; Peilan ZHOU ; Ruibin SU
Chinese Journal of Pharmacology and Toxicology 2014;(3):426-431
OBJECTIVE Toestablisharecombinantcelllinethatcanstablyexpressratpurinergic P2receptorP2X4(rP2X4R).METHODS ToconstructgreenfluorescentproteinandrP2X4recombinant plasmid (pEGFP-N1-rP2X4),lipofectamine was used to transfect pEGFP-N1-rP2X4 into human embry-onic kidney (HEK293)cells that were screened with G41 8 (1 g·L-1 ).The quantitative expression of rP2X4 receptor was verified by qRT-PCR and Western blotting analysis.Whole-cell patch clamp record-ing was used to investigate the function of the stably expressed rP2X4 receptor. RESULTS The sequence of plasmid pEGFP-N1-rP2X4 was verified by PubMed Blastn comparison.qRT-PCR and Western blotting analysis demonstrated that the expression of rP2X4 receptor in HEK293-pEGFP-N1-rP2X4 cell lines remained stable after 25 generations (P1 ,P3,P5,P10,P15,P20 and P25).Whole-cell patch clamp recording experiments showed that the rP2X4 receptor agonist,purine-5′-triphosphate (ATP,3.0 μmol·L-1 ),could activate rP2X4 receptors in HEK293-pEGFP-N1-rP2X4 cell lines.Specific activating current could be blocked by non-selective rP2X4 receptor antagonist TNP-ATP (30.0μmol·L-1).CONCLUSION rP2X4receptorisstablyexpressedinHEK293-pEGFP-N1-rP2X4cell line and maintains stable expression and function within 25 continuous generations.The establish ment of HEK293-pEGFP-N1-rP2X4 cell line can contribute to further investigations of the roles of rP2X4 receptors in neuropathic pain.
4.The role of dopamine transporter in psychostimulant dependence
Guangxiao WU ; Ruibin SU ; Jin LI
Chinese Pharmacological Bulletin 2010;26(2):141-143
Psychostimulant is a type of psychoactive substances that stimulate central and peripheral nervous system as well as induce drug dependence.A series of studies indicate that monoamine especially dopamine plays an important role in behavior and drug dependence,moreover,dopamine transporter(DAT)controls homeostasis of dopamine in neuron and transmission of dopamine pathways.Thus DAT might play an important role in the reward and behavioral stimulation of psychostimulant.
5.Cerebral ischemia and opioids
Gang YU ; Ruibin SU ; Zehui GONG
Chinese Pharmacological Bulletin 1987;0(01):-
Opioid peptides and their receptors play an important r ole in the pathophysiologic process of stroke. The concentration of endogenous o pioid peptides elevates, while the density of opioid receptors decreases in CNS during cerebral ischemia; on the other hand, opioids influence the development o f stroke through regulating the contraction of cerebral vessel, immuno-endocrin e system and neuroprotection against injury. Thus, drugs that regulate the opioi d system may be a new therapeutic approach for prevention and treatment of cereb ral ischemia.
6.Role of retrograde messenger NO in long-term potentiation
Basic & Clinical Medicine 2006;0(09):-
As an important messenger molecule, NO exists in both peripheral and central nervous system (CNS). Recently, NO was proved to play a critical role in CNS, especially in synaptic plasticity. As a kind of retrograde messenger, it plays some roles in the induction and maintenance of LTP through activation of downstream pathway or molecules, such as NO-cGMP-PKG, ADPRT and C-FOS.
7.Mechanism of opioid receptor ubiquitination and its effect on receptor function
Jiebing JLANG ; Peilan ZHOU ; Zhibing ZHENG ; Ruibin SU
Chinese Journal of Pharmacology and Toxicology 2015;(2):302-309
Opioid receptors, as an important member of G protein coupled receptors (GPCR), are the binding targets of endogenous opioid peptides and exogenous opiates. The activation of opioid receptors influences the nervous system, immune physiology and endocrine system. However, prolonged activation of opioid receptors is likely to produce opioid tolerance, leading to opioid addiction. Receptor endocytosis and sorting into the recycling pathway contribute to recovery of cellular opioid responsiveness. Recent studies have revealed that GPCR can be modulated by ubiquitination which plays a unique roles in governing GPCR trafficking. Moreover, ubiquitination of the opioid receptors (μ, κand δ) is increased after stimulation of most opioid agonists. Mutation of the ubiquitin sites affects the internalization and degradation of opioid receptors, which contributes to changes in signal pathways and regulation of opioid receptors. ln this paper, ubiquitination of opioid receptors and the fundamental role of ubiquitination in trafficking of opioid receptors are reviewed.
8.ReIationships between sodium channeI NaV 1.7 and pain
Xiaonan LLANG ; Gang YU ; Zhibing ZHENG ; Ruibin SU
Chinese Journal of Pharmacology and Toxicology 2015;(2):297-301
Voltage-gated sodium channels (NaV1.1-NaV1.9) play important roles in the generation and maintenance of electrical excitability. NaV1.7 is preferentially expressed in peripheral somatic sensory neurons and sympathetic ganglion neurons. ln humans, gain-of-function mutations of SCN9A gene, which encodes NaV1.7, cause inherited neuropathic pain, whereas loss-of-function mutations result in a congenital indifference to pain without motor, cognitive and cardiac deficits. The effects of some analge-sics are associated, at least in part, with the NaV1.7 and selective NaV1.7 inhibitors have also been demonstrated to be analgesic in animal models. NaV1.7 has emerged as a potential target for the treat-ment of pain.
9.Impulsive-like behaviors of rats in Y-maze task induced by pramipexole and its mechanism
Wentao MA ; Xiang GAO ; Zehui GONG ; Zheng YONG ; Ruibin SU
Chinese Journal of Pharmacology and Toxicology 2016;30(5):491-497
OBJECTIVE To analyze impulsive-like behaviors of SD rats induced by pramipexole in Y-maze avoidance tasks. METHODS Behaviors of SD rats in Y-maze avoidance tasks were recorded with a camera and analyzed by Noldus Etho Vision XT8 software after acute subcutaneous injection of pramipexole(0.1,1 and 10 mg · kg-1),including right reaction numbers of 20 consecutive avoidance tasks,shuttle number of times between the three arms of Y-maze, distance covered in Y-maze and time spent in safe arms during 20 consecutive avoidance tasks. Then,the prepulse inhibition(PPI)of the startle reflex test was used to assess the effect of pramipexole on sensorimotor gating (SG). Effects of pramipexole on the dialyzed content of monoamine neurotransmitter and its metabolites in the striatum and amygdala of SD rats were measured by microdialysis in vivo. RESULTS Compared with normal control group,the rats of pramipexole group showed a significant increase in the shuttle number of times and distance covered in Y-maze between Y-maze avoidance tasks(P<0.01),but a statistically significant decrease in the time spent in safe arms(P<0.01),while the number of right reactions in Y-maze avoidance tasks was not changed. Such premature responses were quite similar to certain impulsive-compulsive behaviors in rodent models,such as five-choice serial reaction time tasks. In the PPI test,pramipexole displayed an impairing effect on SG(P<0.01). The microdialysis results showed that there was an increase of dopamine and 5-hydroxytryptamine in the striatum of pramipexole group, but not statistically significant. Monoamine neurotransmitters and their metabolites were not significantly changed in the amygdala. CONCLUSION Pramipexole can induce impulsive-compulsive behaviors in Y-maze avoidance tasks,which might be attributed to impaired SG.
10.Study on Bioavailability of Losartan Potassium Tablets
Ruibin LIU ; Junmin LIU ; Qiguo SU ; Yue HU
China Pharmacy 2007;0(26):-
OBJECTIVE:To study the bioequivalence of 2 kinds of Losartan potassium tablets in healthy volunteers. METHODS: A single oral dose of test tablet 100 mg and reference tablet 100 mg were given to 20 healthy volunteers in randomized crossover study. The plasma concentrations of losartan and its metabolite EXP3174 were determined by LC-MS. The pharmacokinetic parameters were calculated and bioequivalence of 2 kinds of tablets was evaluated. RESULTS: Main pharmacokinetic parameters of Losartan of test tablets vs. reference tablets were as follows: Cmax(534.230?238.642) ng?mL-1 vs.(520.020?226.800) ng?mL-1; tmax(1.401?0.946)h vs.(1.334?0.750)h; AUC0~36(871.177?232.315) ng?h?mL-1 vs. (773.030?252.209) ng?h?mL-1; pharmacokinetic parameters of metabolite EXP3174 of test tablets vs. reference tablets were as follows: Cmax (1 294.000?387.815) ng?mL-1 vs.(1 140.900?317.615)ng?mL-1;tmax(2.667?1.144)h vs.(2.734?1.162)h;AUC0~36(6 267.905?1 350.300)ng?h?mL-1 vs.(5 719.411?1 127.725) ng?h?mL-1; AUC0~∞(6 316.605?1 343.048)ng?h?mL-1 vs. (5 755.335?1 138.358) ng?h?mL-1. The relative bioavailability of test tablet was (116.6?24.3)%. CONCLUSION: 2 kinds of Losartan potassium tablets are bioequivalent.