2.A novel insight into neuroprotection against hypoxic/ischemic stress.
Yuan FENG ; Dongman CHAO ; Xiaozhou HE ; Yilin YANG ; Xuezhi KANG ; Lawrence H LAZARUS ; Ying XIA
Acta Physiologica Sinica 2009;61(6):585-592
The use of opioid analgesics has a long history in clinical settings, although the functions of opioid receptors, especially their role in the brain, are not well understood yet. Recent studies have generated abundant new data on opioid receptor-mediated functions and the underlying mechanisms. The most exciting finding in the past decade is probably the neuroprotection against hypoxic/ischemic stress mediated by delta-opioid receptors (DOR). An up-regulation of DOR expression and the release of endogenous opioids may increase neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers, depending on stress duration and severity, different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of ionic homeostasis, an increase in pro-survival signaling (e.g., PKC-ERK-Bcl 2) and the enhanced anti-oxidative capacity. Recent data on DOR-mediated neuroprotection provide us a new concept of neuroprotection against neurological disorders and have a potentially significant impact on the prevention and treatment of some serious neurological conditions, such as stroke.
Analgesics, Opioid
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pharmacology
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Humans
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Hypoxia
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metabolism
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Neurons
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metabolism
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Neuroprotective Agents
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pharmacology
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Receptors, Opioid, delta
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metabolism
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Signal Transduction
3.µ-opioid receptors in the central nucleus of the amygdala modulate sucrose solution intake in rats.
Bo SUN ; Jianqun YAN ; Qian WANG ; Xiaolin ZHAO ; Jinrong LI ; Wei YAN ; Ke CHEN ; Xuejuan YANG ; Shiru ZHAO ; Junbao YAN
Journal of Southern Medical University 2012;32(4):487-491
OBJECTIVETo explore the role of µ-opioid receptors (MOR) in the central nucleus of the amygdala (CeA) in modulating sucrose solution intake in rats.
METHODSSprague-Dawley rats received intra-CeA injection of MOR agonist DAMGO or saline, and then underwent two bottle choice test between sucrose solution and distilled water. After intake of sucrose solution or distilled water, activated neurons in the CeA were labeled and identified with MOR/Fos-double labeling immunohistochemistry.
RESULTSCompared with saline injection, intra-CeA injection of DAMGO significantly increased sucrose solution intake in rats over a 3-h period. Sucrose solution intake induced significantly more c-Fos and MOR/Fos double-labeled neurons in the CeA than distilled water intake.
CONCLUSIONSThe CeA participates in modulation of sucrose intake in rats, and MOR may partly mediate this mechanism.
Amygdala ; metabolism ; Animals ; Male ; Neurons ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu ; metabolism ; Sucrose ; metabolism
4.The characteristics of opioid receptors distributed in the neurons of habenula.
Sui-sheng WU ; Chun-xiao ZHANG ; Min HUANG ; Xiao-jie CAO ; Shao WANG
Chinese Journal of Applied Physiology 2005;21(1):64-67
AIMTo explore the types of receptors distributed in MHb and LHb.
METHODSRecording the currents of potassium channels in Hb neurons isolated from the rats 10-15 days after birth. To distinguish the types of receptors distributed in MHb and LHb by using the agonists of mu receptor DAMGO, and sigma receptor DPDPE.
RESULTSTwo types of current of K+ channels were recorded, the transient rectifier and delayed rectifier potassium channels. DAMGO or DPDPE increased the intensity of current of K+ channels.
CONCLUSIONIn MHb there was a higher density of sigma receptor, and in LHb a higher density of mu receptor distributed.
Animals ; Animals, Newborn ; Habenula ; metabolism ; Neural Pathways ; Neurons ; metabolism ; Potassium Channels ; metabolism ; Rats ; Receptors, Opioid ; metabolism
5.Design, synthesis and antalgic activities of aralkyl-ketone-4-piperidol derivatives.
Guan WANG ; Gui-sen ZHANG ; Lin GUO ; Jie CHEN ; Jian-qi LI
Acta Pharmaceutica Sinica 2009;44(4):371-378
A series of aralkyl-ketone-4-piperidol derivatives were synthesized and tested for their analgesic activities. All of the novel 30 compounds were prepared from 4-piperidone and alpha-halo-aralkyl-ketone through five steps, including Boc protection, nucleophilic addition in presence of CeCl3/NaI catalyst, deprotection, condensation and salification. Their structures were confirmed by 1H NMR and HRMS. Preliminary in vivo pharmacological trials showed that most of the synthesized compounds revealed analgesic effects. Among the tested compounds, 8, 13 and 22 exhibited potent analgesic activities in both mice writhing and mice hot plate model. The three compounds have low affinity for mu, delta, kappa receptors, which is a chance to find a better precursor of non-opioid analgesic for further optimization.
Analgesics, Non-Narcotic
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chemical synthesis
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chemistry
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pharmacology
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Animals
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Mice
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Molecular Structure
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Pain Measurement
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Pain Threshold
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drug effects
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Piperidones
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chemical synthesis
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chemistry
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pharmacology
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Receptors, Opioid, delta
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metabolism
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Receptors, Opioid, kappa
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metabolism
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Receptors, Opioid, mu
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metabolism
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Structure-Activity Relationship
6.Changs of Kappa opioid receptor expression in central amygdaloid nuclei during the process of chronic morphine-induced conditioned place aversion in rats.
Xiu-Hua SONG ; Jiang-Ling LV ; Wen-Qiang LI ; Jing-Dan ZHANG ; Yu-Zhong SHI ; Rui-Ling ZHANG
Chinese Journal of Applied Physiology 2014;30(5):457-459
7.Synthesis and pharmacology of 8-amino-3-(tetrahydro-2-furanyl)methyl benzomorphan.
Qun ZHOU ; Wen-hu DUAN ; Dana J COHEN ; Jean M BIDLACK ; Mark P WENTLAND
Acta Pharmaceutica Sinica 2003;38(10):748-753
AIMTo design and synthesize new chiral 8-(substituted) amino-analogues of 3-[(tetrahydro-2-furanyl)methyl] benzomorphans, to expand knowledge of the structure-activity relationship (SAR) for 8-aminobenzomorphan.
METHODSTarget compounds were synthesized from the 8-triflate of the optically active 3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphans using Pd-catalyzed aminations. Opioid receptor binding experiments were performed to evaluate their biological activities.
RESULTSBoth 8-amino and 8-phenylamino analogues showed lower binding affinity for mu, delta and kappa receptors than corresponding 8-hydroxy-3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphan in vitro.
CONCLUSIONThe relative poor binding affinity of the target compounds did not warrant conducting the in vivo studies to determine if they have the profile(kappa agonist/mu antagonist) that will be potentially useful in the treatment of drug addiction. Further study is in progress.
Animals ; Benzomorphans ; chemical synthesis ; chemistry ; pharmacology ; Brain ; metabolism ; Furans ; chemical synthesis ; chemistry ; pharmacology ; Guinea Pigs ; Molecular Structure ; Narcotic Antagonists ; chemical synthesis ; chemistry ; pharmacology ; Radioligand Assay ; Receptors, Opioid ; metabolism ; Receptors, Opioid, delta ; metabolism ; Receptors, Opioid, kappa ; metabolism ; Receptors, Opioid, mu ; metabolism ; Structure-Activity Relationship
8.Primary investigation on heterodimerization of kappa-opioid receptor and ORL1 receptor.
Quan WEN ; Ling-di YAN ; Yu-lei LI ; Ze-hui GONG
Acta Pharmaceutica Sinica 2011;46(9):1078-1083
This study investigates whether kappa-opioid receptor and ORL1 receptor may interact to form a heterodimer. In immunofluorescence and co-immunoprecipitation experiments, differentially epitope-tagged receptors, colocalization and heterodimerization of kappa-opioid receptor and ORL1 receptor were used and examined in primary culturing rat neurons, Chinese hamster ovary (CHO) or human embryonic kidney 293 (HEK293) cells. The results show that fluorescence of both kappa-opioid receptor and ORL1 receptor were overlapping in primary culturing hippocampal and cortical neurons. Similarly in co-expressing CHO or HEK293 cells, HA-KOR and Myc-ORL1 were almost exclusively confined to the membranes, revealing extensive colocalization. When Flag-KOR and Myc-ORL1 were co-expressing in CHO cells, heterodimerization was identified to have the ability to co-immunoprecipitate ORL1-receptors with kappa-opioid receptor and vice versa. In the current study, further evidence was provided for the direct interaction of two subtypes of opioid receptors, kappa-opioid receptor and ORL1-receptor, to form the heterodimerization. The finding represents the novel pharmacological mechanism for modulation of opioid receptor function as well as diversity of G protein-coupled receptors.
Animals
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CHO Cells
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Cells, Cultured
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Cerebral Cortex
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cytology
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metabolism
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Cricetinae
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Cricetulus
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Dimerization
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Female
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HEK293 Cells
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Hippocampus
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cytology
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metabolism
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Humans
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Immunoprecipitation
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Male
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Neurons
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cytology
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metabolism
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Rats
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Rats, Wistar
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Receptors, Opioid
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metabolism
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Receptors, Opioid, kappa
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metabolism
9.New Frontiers in Pharmacology.
Yonsei Medical Journal 1979;20(2):87-91
10.Binding characteristics of new synthesized opioid receptor ligands to cloned mu opioid receptors stably expressed in CHO cell.
Ping HU ; Cai-ying YE ; Zhui-bai QIU ; Hui-fen YANG ; De-chang ZHANG
Acta Academiae Medicinae Sinicae 2003;25(1):79-82
OBJECTIVETo determine the affinity of new opioid receptor ligands to cloned mu opioid receptors stably expressed in CHO cell.
METHODSThe binding characteristics of the opioid ligand [3H] diprenorphine (3H-dip) were studied by cellular biological techniques and radioligands binding in cloned mu opioid receptors stably expressed in CHO cells in saturation binding experiments, and were followed by competition binding experiments with a variety of new synthesized opioid receptor ligands.
RESULTSThe Kd and Bmax of [3H] diprenorphine bound to mu receptors were 1.06 nmol/L and 930 fmol/mg protein, respectively. Competition binding experiments revealed that ligand 3# and 12# displayed much higher affinity than DAMGO and Morphine for the cloned mu opioid receptor. However, the affinities of ligands 2#, 6#, 8# and 9# were lower than DAMGO and Morphine.
CONCLUSIONThe present results suggest that the new ligands 3# and 12# have higher affinity to mu opioid receptors. However, ligands 2#, 6#, 8# and 9# have lower affinity to mu opioid receptors.
Animals ; Binding Sites ; Binding, Competitive ; CHO Cells ; metabolism ; Cloning, Molecular ; Cricetinae ; Diprenorphine ; pharmacology ; Ligands ; Receptors, Opioid, mu ; biosynthesis ; genetics ; metabolism