Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals ...Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique.The CB1R antagonist rimonabant(1 or 3 mg/kg,i.p.)was administered either at one hour prior to the sample phase for acquisition,or immediately after the sample phase for consolidation,or at one hour before the test phase for retrieval of NOR memory.For the reconsolidation task,rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition,consolidation,and retrieval,but it did not affect the reconsolidation of NOR memory.Rimonabant administration did not affect acquisition,consolidation,and reconsolidation;however,it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings,along with our previous report,would seem to suggest that RSD may affect different phases of recognition memory based on its duration.Importantly,it seems that the CB1R may,at least in part,be involved in the adverse effects of chronic RSD on the retrieval,but not in the acquisition,consolidation,and reconsolidation,of NOR memory.展开更多
This study investigated the modulatory effect of synthetic cannabinoids WIN55,212-2 on 5-HT3 receptor-activated currents (I5-HT3) in cultured rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique...This study investigated the modulatory effect of synthetic cannabinoids WIN55,212-2 on 5-HT3 receptor-activated currents (I5-HT3) in cultured rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique. The results showed that: (1) The majority of examined neurons (78.70%) were sensitive to 5-HT (3–300 μmol/L). 5-HT induced inward currents in a concentration-dependent manner and the currents were blocked by ICS 205-930 (1 μmol/L), a selective antagonist of the 5-HT3 receptor; (2) Pre-application of WIN55,212-2 (0.01–1 μmol/L) significantly inhibited I5-HT3 reversibly in concentration-dependent and voltage-independent manners. The concentra-tion-response curve of 5-HT3 receptor was shifted downward by WIN55,212-2 without any change of the threshold value. The EC50 values of two curves were very close (17.5±4.5) mmol/L vs. (15.2±4.5) mmol/L and WIN55,212-2 decreased the maximal amplitude of I5-HT3 by (48.65±4.15)%; (3) Neither AM281, a selective CB1 receptor antagonist, nor AM630, a selective CB2 receptor antagonist reversed the inhibition of I5-HT3 by WIN55,212-2; (4) When WIN55,212-2 was given from 15 to 120 s before 5-HT application, inhibitory effect was gradually increased and the maximal inhibition took place at 90 s, and the inhibition remained at the same level after 90 s. We are led to concluded that-WIN55,212-2 inhibited I5-HT3 significantly and neither CB1 receptor antagonist nor CB2 receptor antagonist could reverse the inhibition of I5-HT3 by WIN55,212-2. Moreover, WIN55,212-2 is not an open channel blocker (OCB) of 5-HT3 receptor. WIN55,212-2 significantly inhibited 5-HT-activated currents in a non-competitive manner. The inhibition of I5-HT3 by WIN55,212-2 is probably new one of peripheral analgesic mechanisms of WIN55,212-2, but the mechanism by which WIN55,212-2 inhibits I5-HT3 warrants further investigation.展开更多
A novel and efficient method was developed for the synthesis of diarylpyrazole derivatives as cannabinoid CB1 receptor antagonist via four step reactions. The key step was the synthesis of a diarylpyrazole skeleton, w...A novel and efficient method was developed for the synthesis of diarylpyrazole derivatives as cannabinoid CB1 receptor antagonist via four step reactions. The key step was the synthesis of a diarylpyrazole skeleton, which involved initial condensation of the sodium salt of compound 12 with diazonium compounds, and further cyclization by heating at reflux in acetic acid. Eight diarylpyrazole derivatives and nine new synthesized compounds were characterized by 1H NMR, IR, MS, and elemental analysis. The reaction conditions were mild and the overall yields of the target compounds ranged from 26% to 44%.展开更多
目的:吸烟在全世界引起了严重的健康问题,全球约5百万早产儿死于吸烟。此外,吸烟是一种以戒断后反复复吸为特点的慢性复发性疾病。尼古丁是烟草中导致人类成瘾的主要成分,可以使啮齿类动物形成持续的自身给药行为和条件性位置偏爱(CPP)...目的:吸烟在全世界引起了严重的健康问题,全球约5百万早产儿死于吸烟。此外,吸烟是一种以戒断后反复复吸为特点的慢性复发性疾病。尼古丁是烟草中导致人类成瘾的主要成分,可以使啮齿类动物形成持续的自身给药行为和条件性位置偏爱(CPP)。大量数据表明内源性大麻系统在尼古丁成瘾神经机制中有重要的作用。阻断CB1受体减少了尼古丁自身给药,线索诱导的尼古丁渴求的再现,以及尼古丁诱导的CPP。然而,最近的数据提示URB597通过抑制脂肪酸酰胺水解酶(fat acid amide hydrolase,FAAH)增强anandamide的传递,进而减少尼古丁关联行为,如尼古丁自身给药行为的获得和再现,尼古丁诱导大鼠CPP的表达和再现(Scherma et al.,2008)。CB1受体拮抗剂利莫他班对尼古丁自身给药累进比率(progressive ratio,PR),尼古丁点燃诱导的复吸,以及URB597对线索诱导尼古丁渴求再现的作用尚没有研究报道。本研究旨在填补这一空白。方法:大鼠在形成稳定的尼古丁累进自身给药行为后,观察利莫他班急性(0.3-3mg·kg-1,ip)或反复给药(1mg·kg-1,ip)对尼古丁转换点(breaking point)的作用。该测试完成后,所有的大鼠进行消退训练。我们比较了自身给药行为消退后URB597不可逆地选择性抑制FAAH和选择性CB1受体拮抗剂利莫他班两种干预对线索诱导的和尼古丁点燃(0.15mg·kg-1,sc)诱导的尼古丁复吸行为再现的作用。结果:利莫他班(0.3-3mg·kg-1)剂量依赖性的减少了尼古丁的转换点,1mg·kg-1的利莫他班的作用稳定。在尼古丁给药行为消退后,尼古丁点燃和尼古丁相关线索可以再现尼古丁自身给药行为。利莫他班(1mg·kg-1)和URB597(0.3 and 1mg·kg-1)显著减少了这种自身给药行为的再现。结论:本研究结果显示DB1受体的完整性是尼古丁自身给药行为动机所必需的,利莫他班可以稳定的减少这种行为。利莫他班阻断CB1受体或者通过抑制FAAH活性增强anandamide水平都减少了尼古丁渴求行为的再现。URB597的这些作用提示anadamide可能在尼古丁渴求中起抑制性的作用;这个假设还需要进一步研究介导尼古丁渴求的多种内源性大麻物质的功能。既然利莫他班在戒烟和复吸的使用上受精神副作用的限制,我们的结果提示更精确的靶相调节大麻系统可能可以预防戒烟者的复吸。展开更多
Background: Cannabinoid receptor subtype 1 (CB1) has a relationship to the proliferation of various cells including malignant tumoral cells. We investigated and compared the expression of CB1 in benign and malignant h...Background: Cannabinoid receptor subtype 1 (CB1) has a relationship to the proliferation of various cells including malignant tumoral cells. We investigated and compared the expression of CB1 in benign and malignant human prostate tissues and in benign and malignant human prostate cell lines, as well as its function for the proliferation of human prostate cancer cells. Methods: Real-time quantitative PCR was performed to compare its expressions in human prostate tissues (normal, benign hyperplasia, and cancer) and prostate cell lines (3 normal and 3 malignant). For localization of CB1, immunofluorescent staining with rabbit anti-CB1 polyclonal antibodies and tetramethyl isothiocyanate (TRITC)-labeled swine anti-rabbit immunoglobulin (DAKO) were used under fluorescence microscope. To further analyze whether cell death was induced by anandamide (non-selective agonist for CB1/CB2) via a receptor dependent mechanism, the viability of DU145 cells, which is known as androgen-insensitive prostate cancer cell, was measured using MTT assay. Results: CB1mRNA was found to be expressed in the all 3 human prostate tissues, however, CB1 protein was expressed in BPH and low grade malignant PC tissues, but not in high grade malignant PC tissues. CB1 as for cell lines, the expression of CB1 was low in malignant cell lines except for DU145. Anandamide elicited cell death, which was significantly inhibited by AM251 (selective antagonist for CB1), indicating that cell death induced by anandamide in DU145 cells was mediated by CB1. Anandamide time-dependently elicits up-regulation of CB1 in DU145 cells. Conclusions: CB1 may be an inhibitory regulator of androgen-insensitive human prostate cancer epithelial cell growth.展开更多
Background:The expression,localization,and function of the endocannabinoid system has been well characterized in recent years in the monkey retina and in the primary thalamic relay,the lateral geniculate nucleus(dLGN)...Background:The expression,localization,and function of the endocannabinoid system has been well characterized in recent years in the monkey retina and in the primary thalamic relay,the lateral geniculate nucleus(dLGN).Few data are available on cortical recipients’structures of the dLGN,namely the primary visual cortex(V1).The goal of this study is to characterize the expression and localization of the metabotropic cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1.Methods:Using Western blots and immunohistochemistry,we investigated the expression patterns of CB1R,NAPE-PLD,and FAAH in the vervet monkey primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in the primary visual cortex throughout the rostro-caudal axis.CB1R showed very low levels of staining in cortical layer 4,with higher expressions in all other cortical layers,especially layer 1.NAPE-PLD and FAAH expressions were highest in layers 1,2 and 3,and lowest in layer 4.Conclusions:Interestingly enough,CB1R was very low in layer 4 of V1 in comparison to the other cortical layers.The visual information coming from the dLGN and entering layer 4Calpha(magno cells)and 4Cbeta(parvo cells)may be therefore modulated by the higher expression levels of CB1R in cortical layers 2 and 3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in the outer cortical layers.These data indicate that CB1R system can influence the network of activity patterns in the visual stream after the visual information has reached area V1.These novel results provide insights for understanding the role of the endocannabinoids in the modulation of cortical visual inputs,and hence,visual perception.展开更多
Background:The goal of this study is to determine the expression and localization of the cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the deg...Background:The goal of this study is to determine the expression and localization of the cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1 to better understand the mechanisms underlying the effects of eCB system modulation on cortical visual processing.Methods:Using Western blots and immunohistochemistry,we investigated the laminar and cellular expression patterns of CB1R,NAPE-PLD,and FAAH across the rostrocaudal axis of the vervet monkey(Chlorocebus sabaeus)primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in V1 throughout the rostrocaudal axis.CB1R showed very low staining in layer(L)4,with higher expression in all other layers,especially L1,followed by L2 and L3.NAPE-PLD and FAAH expression patterns were similar,but not quite as low in L4.CB1R,NAPE-PLD,and FAAH were localized in vGlut2-positive cells,representing glutamatergic projection neurons,and in somatostatin(SST)-positive cells,a class of GABAergic interneurons.Conclusions:The low level of CB1R in L4 indicates less direct endocannabinoid modulation of V1 afferents from the dLGN,but that greater modulation may occur via the higher expression of CB1R in L2 and L3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in these layers.Expression in vGlut2-positive and SST-positive cells represents a role at both glutamatergic and GABAergic neurons.These data indicate that CB1R may influence the network of activity patterns in the visual streams after the visual information has reached V1,and thus may influence visual perception.展开更多
背景:大麻素受体通过与配体结合,调控牙周炎的炎症和骨量,促进牙周组织的愈合,在临床上牙周炎的预防和治疗方面具有重要意义。目的:综述大麻素受体与牙周炎的关系,主要为大麻素Ⅰ型(CB1)受体、大麻素Ⅱ型(CB2)受体与炎症和牙槽骨骨改建...背景:大麻素受体通过与配体结合,调控牙周炎的炎症和骨量,促进牙周组织的愈合,在临床上牙周炎的预防和治疗方面具有重要意义。目的:综述大麻素受体与牙周炎的关系,主要为大麻素Ⅰ型(CB1)受体、大麻素Ⅱ型(CB2)受体与炎症和牙槽骨骨改建的关系,以及涉及的常见细胞信号传导通路,为牙周炎预防和治疗及其在临床其他领域的应用提供思路。方法:检索PubMed、万方数据库、CNKI中国期刊全文数据库1985年7月至2022年7月收录的相关文献。英文检索词为“cannabinoids receptor,CB1 receptor and periodontitis,CB2 receptor and periodontitis,CB1 receptors and bone remodeling,CB2 receptors and bone remodeling,CB1 receptors and signaling pathways,CB2 receptors and signaling pathways”,中文检索词为“大麻素受体,CB1受体和牙周炎,CB2受体和牙周炎,CB1受体和骨改建,CB2受体和骨改建,CB1受体和信号通路、CB2受体和信号通路”,最终纳入107篇文献进行归纳总结。结果与结论:①内源性大麻素系统包含多种受体,其中最具有代表性的为CB1和CB2受体,均属于G蛋白偶联超家族成员;二者在牙周组织中均存在表达;②在天然配体或人工合成激动剂的作用下,大麻素受体可通过不同的代谢通路在体内外产生特定的生理效应,从而调控牙周炎局部的炎症和骨细胞的生成和分化,最终影响炎症和骨量;③进一步研究大麻素受体与牙周炎炎症和牙槽骨骨形成、骨吸收的关系,以及涉及到的常见信号通路——丝裂原活化蛋白激酶(MAPK)信号通路、NF-κB信号通路,为临床上牙周炎的预防和治疗提供新的思路成为目前研究的重点。展开更多
基金Supported by the Research Council of Kermanshah University of Medical Sciences,Kermanshah,Iran for financial support(grant no.:990812).
文摘Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique.The CB1R antagonist rimonabant(1 or 3 mg/kg,i.p.)was administered either at one hour prior to the sample phase for acquisition,or immediately after the sample phase for consolidation,or at one hour before the test phase for retrieval of NOR memory.For the reconsolidation task,rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition,consolidation,and retrieval,but it did not affect the reconsolidation of NOR memory.Rimonabant administration did not affect acquisition,consolidation,and reconsolidation;however,it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings,along with our previous report,would seem to suggest that RSD may affect different phases of recognition memory based on its duration.Importantly,it seems that the CB1R may,at least in part,be involved in the adverse effects of chronic RSD on the retrieval,but not in the acquisition,consolidation,and reconsolidation,of NOR memory.
基金supported by National Natural Science Foundation of China(No.30271500)Science and Tech-nology Research Project Fund from the Department of Edu-cation of Hubei Province of China(No.B20115101)
文摘This study investigated the modulatory effect of synthetic cannabinoids WIN55,212-2 on 5-HT3 receptor-activated currents (I5-HT3) in cultured rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique. The results showed that: (1) The majority of examined neurons (78.70%) were sensitive to 5-HT (3–300 μmol/L). 5-HT induced inward currents in a concentration-dependent manner and the currents were blocked by ICS 205-930 (1 μmol/L), a selective antagonist of the 5-HT3 receptor; (2) Pre-application of WIN55,212-2 (0.01–1 μmol/L) significantly inhibited I5-HT3 reversibly in concentration-dependent and voltage-independent manners. The concentra-tion-response curve of 5-HT3 receptor was shifted downward by WIN55,212-2 without any change of the threshold value. The EC50 values of two curves were very close (17.5±4.5) mmol/L vs. (15.2±4.5) mmol/L and WIN55,212-2 decreased the maximal amplitude of I5-HT3 by (48.65±4.15)%; (3) Neither AM281, a selective CB1 receptor antagonist, nor AM630, a selective CB2 receptor antagonist reversed the inhibition of I5-HT3 by WIN55,212-2; (4) When WIN55,212-2 was given from 15 to 120 s before 5-HT application, inhibitory effect was gradually increased and the maximal inhibition took place at 90 s, and the inhibition remained at the same level after 90 s. We are led to concluded that-WIN55,212-2 inhibited I5-HT3 significantly and neither CB1 receptor antagonist nor CB2 receptor antagonist could reverse the inhibition of I5-HT3 by WIN55,212-2. Moreover, WIN55,212-2 is not an open channel blocker (OCB) of 5-HT3 receptor. WIN55,212-2 significantly inhibited 5-HT-activated currents in a non-competitive manner. The inhibition of I5-HT3 by WIN55,212-2 is probably new one of peripheral analgesic mechanisms of WIN55,212-2, but the mechanism by which WIN55,212-2 inhibits I5-HT3 warrants further investigation.
基金Supported by the Program for New Century Excellent Talents in University of China(NosNCET-08-0668, 1154-NCET-002)the Outstanding Youth Foundation of Heilongjiang Province, China(NoJC200706)
文摘A novel and efficient method was developed for the synthesis of diarylpyrazole derivatives as cannabinoid CB1 receptor antagonist via four step reactions. The key step was the synthesis of a diarylpyrazole skeleton, which involved initial condensation of the sodium salt of compound 12 with diazonium compounds, and further cyclization by heating at reflux in acetic acid. Eight diarylpyrazole derivatives and nine new synthesized compounds were characterized by 1H NMR, IR, MS, and elemental analysis. The reaction conditions were mild and the overall yields of the target compounds ranged from 26% to 44%.
文摘目的:吸烟在全世界引起了严重的健康问题,全球约5百万早产儿死于吸烟。此外,吸烟是一种以戒断后反复复吸为特点的慢性复发性疾病。尼古丁是烟草中导致人类成瘾的主要成分,可以使啮齿类动物形成持续的自身给药行为和条件性位置偏爱(CPP)。大量数据表明内源性大麻系统在尼古丁成瘾神经机制中有重要的作用。阻断CB1受体减少了尼古丁自身给药,线索诱导的尼古丁渴求的再现,以及尼古丁诱导的CPP。然而,最近的数据提示URB597通过抑制脂肪酸酰胺水解酶(fat acid amide hydrolase,FAAH)增强anandamide的传递,进而减少尼古丁关联行为,如尼古丁自身给药行为的获得和再现,尼古丁诱导大鼠CPP的表达和再现(Scherma et al.,2008)。CB1受体拮抗剂利莫他班对尼古丁自身给药累进比率(progressive ratio,PR),尼古丁点燃诱导的复吸,以及URB597对线索诱导尼古丁渴求再现的作用尚没有研究报道。本研究旨在填补这一空白。方法:大鼠在形成稳定的尼古丁累进自身给药行为后,观察利莫他班急性(0.3-3mg·kg-1,ip)或反复给药(1mg·kg-1,ip)对尼古丁转换点(breaking point)的作用。该测试完成后,所有的大鼠进行消退训练。我们比较了自身给药行为消退后URB597不可逆地选择性抑制FAAH和选择性CB1受体拮抗剂利莫他班两种干预对线索诱导的和尼古丁点燃(0.15mg·kg-1,sc)诱导的尼古丁复吸行为再现的作用。结果:利莫他班(0.3-3mg·kg-1)剂量依赖性的减少了尼古丁的转换点,1mg·kg-1的利莫他班的作用稳定。在尼古丁给药行为消退后,尼古丁点燃和尼古丁相关线索可以再现尼古丁自身给药行为。利莫他班(1mg·kg-1)和URB597(0.3 and 1mg·kg-1)显著减少了这种自身给药行为的再现。结论:本研究结果显示DB1受体的完整性是尼古丁自身给药行为动机所必需的,利莫他班可以稳定的减少这种行为。利莫他班阻断CB1受体或者通过抑制FAAH活性增强anandamide水平都减少了尼古丁渴求行为的再现。URB597的这些作用提示anadamide可能在尼古丁渴求中起抑制性的作用;这个假设还需要进一步研究介导尼古丁渴求的多种内源性大麻物质的功能。既然利莫他班在戒烟和复吸的使用上受精神副作用的限制,我们的结果提示更精确的靶相调节大麻系统可能可以预防戒烟者的复吸。
文摘Background: Cannabinoid receptor subtype 1 (CB1) has a relationship to the proliferation of various cells including malignant tumoral cells. We investigated and compared the expression of CB1 in benign and malignant human prostate tissues and in benign and malignant human prostate cell lines, as well as its function for the proliferation of human prostate cancer cells. Methods: Real-time quantitative PCR was performed to compare its expressions in human prostate tissues (normal, benign hyperplasia, and cancer) and prostate cell lines (3 normal and 3 malignant). For localization of CB1, immunofluorescent staining with rabbit anti-CB1 polyclonal antibodies and tetramethyl isothiocyanate (TRITC)-labeled swine anti-rabbit immunoglobulin (DAKO) were used under fluorescence microscope. To further analyze whether cell death was induced by anandamide (non-selective agonist for CB1/CB2) via a receptor dependent mechanism, the viability of DU145 cells, which is known as androgen-insensitive prostate cancer cell, was measured using MTT assay. Results: CB1mRNA was found to be expressed in the all 3 human prostate tissues, however, CB1 protein was expressed in BPH and low grade malignant PC tissues, but not in high grade malignant PC tissues. CB1 as for cell lines, the expression of CB1 was low in malignant cell lines except for DU145. Anandamide elicited cell death, which was significantly inhibited by AM251 (selective antagonist for CB1), indicating that cell death induced by anandamide in DU145 cells was mediated by CB1. Anandamide time-dependently elicits up-regulation of CB1 in DU145 cells. Conclusions: CB1 may be an inhibitory regulator of androgen-insensitive human prostate cancer epithelial cell growth.
文摘Background:The expression,localization,and function of the endocannabinoid system has been well characterized in recent years in the monkey retina and in the primary thalamic relay,the lateral geniculate nucleus(dLGN).Few data are available on cortical recipients’structures of the dLGN,namely the primary visual cortex(V1).The goal of this study is to characterize the expression and localization of the metabotropic cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1.Methods:Using Western blots and immunohistochemistry,we investigated the expression patterns of CB1R,NAPE-PLD,and FAAH in the vervet monkey primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in the primary visual cortex throughout the rostro-caudal axis.CB1R showed very low levels of staining in cortical layer 4,with higher expressions in all other cortical layers,especially layer 1.NAPE-PLD and FAAH expressions were highest in layers 1,2 and 3,and lowest in layer 4.Conclusions:Interestingly enough,CB1R was very low in layer 4 of V1 in comparison to the other cortical layers.The visual information coming from the dLGN and entering layer 4Calpha(magno cells)and 4Cbeta(parvo cells)may be therefore modulated by the higher expression levels of CB1R in cortical layers 2 and 3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in the outer cortical layers.These data indicate that CB1R system can influence the network of activity patterns in the visual stream after the visual information has reached area V1.These novel results provide insights for understanding the role of the endocannabinoids in the modulation of cortical visual inputs,and hence,visual perception.
文摘Background:The goal of this study is to determine the expression and localization of the cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1 to better understand the mechanisms underlying the effects of eCB system modulation on cortical visual processing.Methods:Using Western blots and immunohistochemistry,we investigated the laminar and cellular expression patterns of CB1R,NAPE-PLD,and FAAH across the rostrocaudal axis of the vervet monkey(Chlorocebus sabaeus)primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in V1 throughout the rostrocaudal axis.CB1R showed very low staining in layer(L)4,with higher expression in all other layers,especially L1,followed by L2 and L3.NAPE-PLD and FAAH expression patterns were similar,but not quite as low in L4.CB1R,NAPE-PLD,and FAAH were localized in vGlut2-positive cells,representing glutamatergic projection neurons,and in somatostatin(SST)-positive cells,a class of GABAergic interneurons.Conclusions:The low level of CB1R in L4 indicates less direct endocannabinoid modulation of V1 afferents from the dLGN,but that greater modulation may occur via the higher expression of CB1R in L2 and L3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in these layers.Expression in vGlut2-positive and SST-positive cells represents a role at both glutamatergic and GABAergic neurons.These data indicate that CB1R may influence the network of activity patterns in the visual streams after the visual information has reached V1,and thus may influence visual perception.
文摘背景:大麻素受体通过与配体结合,调控牙周炎的炎症和骨量,促进牙周组织的愈合,在临床上牙周炎的预防和治疗方面具有重要意义。目的:综述大麻素受体与牙周炎的关系,主要为大麻素Ⅰ型(CB1)受体、大麻素Ⅱ型(CB2)受体与炎症和牙槽骨骨改建的关系,以及涉及的常见细胞信号传导通路,为牙周炎预防和治疗及其在临床其他领域的应用提供思路。方法:检索PubMed、万方数据库、CNKI中国期刊全文数据库1985年7月至2022年7月收录的相关文献。英文检索词为“cannabinoids receptor,CB1 receptor and periodontitis,CB2 receptor and periodontitis,CB1 receptors and bone remodeling,CB2 receptors and bone remodeling,CB1 receptors and signaling pathways,CB2 receptors and signaling pathways”,中文检索词为“大麻素受体,CB1受体和牙周炎,CB2受体和牙周炎,CB1受体和骨改建,CB2受体和骨改建,CB1受体和信号通路、CB2受体和信号通路”,最终纳入107篇文献进行归纳总结。结果与结论:①内源性大麻素系统包含多种受体,其中最具有代表性的为CB1和CB2受体,均属于G蛋白偶联超家族成员;二者在牙周组织中均存在表达;②在天然配体或人工合成激动剂的作用下,大麻素受体可通过不同的代谢通路在体内外产生特定的生理效应,从而调控牙周炎局部的炎症和骨细胞的生成和分化,最终影响炎症和骨量;③进一步研究大麻素受体与牙周炎炎症和牙槽骨骨形成、骨吸收的关系,以及涉及到的常见信号通路——丝裂原活化蛋白激酶(MAPK)信号通路、NF-κB信号通路,为临床上牙周炎的预防和治疗提供新的思路成为目前研究的重点。
