大麻素受体和配体对胃肠运动及分泌的影响

内源性大麻素系统有几种受体,在体内均存在相应的配体和特定的合成及代谢通路,均属G蛋白耦联超家族成员.近来的一些研究显示,大麻素受体激活后可影响胃肠运动及分泌.本文介绍大麻素的种类,其受体、配体、拮抗剂以及它们对胃肠运动和胃肠分泌的影响,为进一步研究内源性大麻素系统对胃肠运动及分泌的作用机制提供资料,并为临床应用该类药物...     

内源性大麻素系统的研究进展

内源性大麻素物质及其受体在人体内有广泛的生理学作用，与镇痛、免疫调节、心血管、能量代谢等有关，并参与一些疾病的病理过程。对内源性大麻素系统的研究不仅能阐明一些疾病的病理机制，还有助于新药的研发，为相关疾病的治疗提供新的方向。     

大麻素在认知功能障碍中的作用

背景 术后认知功能障碍(postoperative cognitive dysfunction,POCD)是手术后常见并发症之一,不仅导致患者康复延迟,增加医疗费用,而且严重影响患者术后生活质量.研究显示POCD的发生可能是多种机制作用的结果,主要与中枢胆碱能系统、应激反应及炎症反应有关.近年来研究发现大麻素系统在认知功能障碍中也扮演着重要角色. 目的 综述大麻素在认知功能障碍中的作用研究进展. 内容 简介POCD以及大麻素系统,总结目前对于大麻素与认知功能关系的研究成果. 趋向 为研究者提供最新信息,期望对于POCD发病机制的研究提供帮助.     

内源性大麻素系统与神经保护

内源性大麻素系统包括大麻素受体、内源性配体以及参与其降解的酶类。内源性大麻素系统在中枢神经系统的许多病理和生理过程中都扮演重要的角色。大麻素不仅在动物实验研究中被发现具有神经保护作用。在细胞水平,也同样能够促进神经元的存活,大麻素通过许多不同的通路发挥其神经保护作用。包括减少细胞钙内流,抑制谷氨酸能神经传递、抗氧化以及抗炎作用等。本文基玗现有的研究报道,就内源性大麻素系统及其神经保护作用机制进行综述,以便更清楚地认识大麻素在神经保护方面的药理学作用和临床意义。     

内源性大麻素系统对老年骨质疏松症的影响

骨质疏松症是一种常见的老年疾病, 影响着全球数百万患者, 现已成为阻滞健康老龄化进程的主要问题, 研发新的治疗老年骨质疏松症的药物具有重要意义。内源性大麻素系统包含大麻素配体、内源性大麻素受体及合成和降解内源性大麻素所需的酶, 在骨代谢中起着重要的作用。在动物模型和体外实验中使用基于内源性大麻素系统疗法的临床前研究表明内源性大麻素系统可以预防老年骨质疏松症, 并显示出了其对老年骨质疏松症的治疗潜力。通过检索PubMed、ScienceDirect、中国知网及万方数据库收录的有关内源性大麻素系统和骨质疏松症相关研究的文章, 分析老年骨质疏松症的发病机制(如钙、活性维生素D3缺乏或不足、性激素缺乏、细胞功能衰退及慢性疾病继发引起等), 综述近年来内源性大麻素系统的各种成分、其通过调节成骨细胞和破骨细胞的功能影响骨稳态以及在骨质疏松症治疗中的应用进展, 为老年骨质疏松症的临床治疗提供新的方向。     

内源性大麻素系统调节瘙痒的研究进展

背景 很多药物和疾病都能引起瘙痒,但目前有关瘙痒的病理生理学还不完全清楚.研究发现,内源性大麻素系统在调节瘙痒中起着重要的作用,影响着瘙痒的发生与发展.目的 就近年来国内外有关内源性大麻素系统调节瘙痒的文献作一综述. 内容 大麻素受体1 (cannabinoid receptor 1,CB1)激动剂缓解瘙痒,拮抗剂诱发瘙痒.大麻素受体2(cannabinoid receptor 2,CB2)拮抗剂、内源性大麻素类化合物和脂肪酰胺水解酶(fatty acid amide hydrolase,FAAH)间接抑制瘙痒.此外,内源性大麻素的止痒作用可能部分是通过瞬时受体电位香草类受体(transient receptor potential vanilloid type,TRPV)介导的.趋向 内源性大麻素系统可能成为将来各种病因学全身性瘙痒的止痒靶点,但其调节瘙痒的机制还不十分清楚,需要进一步的研究和探讨.     

内源性大麻素系统的研究进展

内源性大麻素及其受体在人体内广泛分布,参与到诸多生理和病理生理过程．对萁代谢和功能的研究受到越来越多的重视。对内源性大麻素系统的研究不仅能阐明一些疾病的病理生理机制,还有助于新药研发并为疾病治疗提供新的方向。     

大麻素类物质应用于骨关节炎疼痛治疗

骨关节炎是一种可导致关节慢性疼痛、畸形和活动障碍的疾病。其中,慢性疼痛是影响患者生活质量的重要原因之一。然而,治疗骨关节炎慢性疼痛的药物并不能令人完全满意。大麻素类物质用于治疗疼痛已有数千年历史,其主要包括内源性大麻素、植物源性大麻素和人工合成大麻素。临床前研究表明,大麻素类物质在骨关节炎疼痛动物模型中具有良好治疗效果,但也存在一些不良反应。该文对近年来大麻素类物质应用于骨关节炎疼痛治疗的研究进展作一综述。     

大麻素受体及其配体对骨量和骨改建的调节作用

内源性大麻素(CB)系统至少有2种受体,在体内均存在相应的配体和特定的合成及代谢通路,均属G蛋白偶联超家族成员.CB1受体主要分布在中枢神经系统,CB2受体主要分布于外周免疫细胞表面,两者受激动均可产生特定的生理反应.研究表明一些CB类物质可在体内抑制类风湿性关节炎的炎症病变.近来对CB受体基因敲除的小鼠研究显示,CB1受体、CB2受体及其配体,其激动剂可在体内外调节破骨细胞及成骨细胞的功能,从而对骨量和骨改建起调节作用.进一步研究其对骨细胞的作用机制,可为临床应用该类药物提供理论依据.     

针刺抗炎研究进展

背景 创伤、烧伤、手术等容易导致机体发生全身炎性反应综合征、脓毒症、多器官功能不全综合征(multiple organ disfunction syndrome,MODS),甚至死亡.调控过度的炎症反应是防治脓毒症和MODS的重要手段之一. 目的 阐释针刺抗炎的作用及机制. 内容 针刺对多种炎性疾病有良好的治疗作用,对脓毒症和MODS亦有一定的防治作用.针刺可通过对免疫细胞、免疫球蛋白、神经递质和细胞因子等的调节,发挥抗炎作用.此外,下丘脑-垂体-肾上腺轴、胆碱能抗炎通路和内源性大麻素系统参与了针刺的抗炎机制. 趋向 针刺抗炎的确切机制尚不清楚,是否还有其他机制参与针刺的抗炎作用还有待阐明.     

Differential effects of endocannabinoids on glutamatergic and GABAergic inputs to layer 5 pyramidal neurons

Endocannabinoids are emerging as potent modulators of neuronal activity throughout the brain, and activation of the type-1 cannabinoid receptor (CB1R) reduces sensory-evoked cortical responses in vivo, presumably by decreasing excitatory transmission. In the neocortex, CB1R is differentially expressed across neocortical laminae, with highest levels of expression in layers 2/3 and 5. Although we have shown that cannabinoid signaling in layer 2/3 of somatosensory cortex targets both gamma-aminobutyric acid (GABA) and glutamate release, the predominant effect is a net increase in pyramidal neuron (PN) activity due to disinhibition. The role of endocannabinoid signaling in layer 5, the main output layer of the neocortex, remains unknown. We found that inducing activity in layer 5 PNs resulted in endocannabinoid-mediated depolarization-induced suppression of excitation (DSE), whereas the majority of inhibitory inputs were cannabinoid insensitive. Furthermore, in contrast to layer 2/3, the net effect of elevations in action potential firing of layer 5 PNs was an endocannabinoid-mediated decrease in PN spike probability. Interestingly, excitatory synaptic currents in layer 5 evoked by intralaminar stimulation were cannabinoid sensitive, whereas inputs evoked from layer 2/3 were insensitive, suggesting specificity of cannabinoid signaling across glutamatergic inputs. Thus, cannabinoids have differential effects on excitation and inhibition across cortical layers, and endocannabinoid signaling in layer 5 may serve to selectively decrease the efficacy of a subset of excitatory inputs.     

Interstitial cells in the human prostate: A new therapeutic target?

BACKGROUND: Interstitial cells have been described in different human organs, including gut and bladder. In the gut they function as pacemaker cells, generating slow wave potentials. Absence or defects in these cells result in motility disorders. In the bladder these cells express the vanilloid receptor and may contribute to the working mechanism of vanilloid therapy. Recently, slow wave potentials and interstitial cells were described in the guinea-pig prostate. In this study we describe the presence of interstitial cells in the human prostate gland. METHODS: We performed immunohistochemical staining for c-kit, vanilloid receptor (VR1), cannabinoid receptor (CB1) connexin43, and neurofilament on fresh frozen tissue from 14 prostatectomy specimens. RESULTS: A large number of cells with a stellate aspect were noticed under the basal layer of the prostatic duct system and in between the smooth muscle cells. They were immunoreactive for c-kit, VR1, and connexin43 but not to CB1 or neurofilament. CONCLUSIONS: There is evidence for interstitial cells in the human prostate. Taken together their topography and immunohistochemical characterization, the discovery of slow wave potentials in guinea pig prostate and the knowledge of interstitial cells in other organs, interstitial cells are likely to be involved in normal prostate physiology.     

Paracetamol (Acetaminophen): mechanisms of action

Paracetamol has a central analgesic effect that is mediated through activation of descending serotonergic pathways. Debate exists about its primary site of action, which may be inhibition of prostaglandin (PG) synthesis or through an active metabolite influencing cannabinoid receptors. Prostaglandin H(2) synthetase (PGHS) is the enzyme responsible for metabolism of arachidonic acid to the unstable PGH(2). The two major forms of this enzyme are the constitutive PGHS-1 and the inducible PGHS-2. PGHS comprises of two sites: a cyclooxygenase (COX) site and a peroxidase (POX) site. The conversion of arachidonic acid to PGG(2) is dependent on a tyrosine-385 radical at the COX site. Formation of a ferryl protoporphyrin IX radical cation from the reducing agent Fe(3+) at the POX site is essential for conversion of tyrosine-385 to its radical form. Paracetamol acts as a reducing cosubstrate on the POX site and lessens availability of the ferryl protoporphyrin IX radical cation. This effect can be reduced in the presence of hydroperoxide-generating lipoxygenase enzymes within the cell (peroxide tone) or by swamping the POX site with substrate such as PGG(2). Peroxide tone and swamping explain lack of peripheral analgesic effect, platelet effect, and anti-inflammatory effect by paracetamol. Alternatively, paracetamol effects may be mediated by an active metabolite (p-aminophenol). p-Aminophenol is conjugated with arachidonic acid by fatty acid amide hydrolase to form AM404. AM404 exerts effect through cannabinoid receptors. It may also work through PGHS, particularly in areas of the brain with high concentrations of fatty acid amide hydrolase.     

Spinal Cannabinoid Receptor Type 2 Activation Reduces Hypersensitivity and Spinal Cord Glial Activation after Paw Incision

Background: Cannabinoids bind to cannabinoid receptors type 1 and 2 and produce analgesia in several pain models, but central side effects from cannabinoid 1 receptors limit their clinical use. Cannabinoid 2 receptors reduce inflammatory responses in the periphery by acting on immune cells, and they are present on glia in the central nervous system. This study tested whether spinal cannabinoid activation would induce analgesia, glial inhibition, and central side effects in a postoperative model or incisional pain.

Methods: Rats underwent paw incision surgery, with intrathecal injections of cannabinoid agonists and antagonists and assessment of withdrawal thresholds and behavioral side effects. Spinal glial activation was determined by immunohistochemistry.

Results: Intrathecal administration CP55940 reduced postoperative hypersensitivity (91 +/- 9% maximum possible effect; P < 0.05), and this was prevented by intrathecal administration of both cannabinoid 1 receptor (AM281) and cannabinoid 2 receptor (AM630) antagonists. CP55940 also caused several behavioral side effects, and these were prevented by the cannabinoid 1 receptor but not by the cannabinoid 2 receptor antagonist. Intrathecal injection of the cannabinoid 2 receptor agonist JWH015 reversed postoperative hypersensitivity (89 +/- 5% maximum possible effect; P < 0.05), and this was reversed by the cannabinoid 2 but not by the cannabinoid 1 receptor antagonist. JWH015, which did not induce behavioral side effects, reduced paw incision induced microglial and astrocytic activation in spinal cord (P < 0.05).     

Spinal cannabinoid receptor type 2 activation reduces hypersensitivity and spinal cord glial activation after paw incision

BACKGROUND: Cannabinoids bind to cannabinoid receptors type 1 and 2 and produce analgesia in several pain models, but central side effects from cannabinoid 1 receptors limit their clinical use. Cannabinoid 2 receptors reduce inflammatory responses in the periphery by acting on immune cells, and they are present on glia in the central nervous system. This study tested whether spinal cannabinoid activation would induce analgesia, glial inhibition, and central side effects in a postoperative model or incisional pain. METHODS: Rats underwent paw incision surgery, with intrathecal injections of cannabinoid agonists and antagonists and assessment of withdrawal thresholds and behavioral side effects. Spinal glial activation was determined by immunohistochemistry. RESULTS: Intrathecal administration CP55940 reduced postoperative hypersensitivity (91 +/- 9% maximum possible effect; P < 0.05), and this was prevented by intrathecal administration of both cannabinoid 1 receptor (AM281) and cannabinoid 2 receptor (AM630) antagonists. CP55940 also caused several behavioral side effects, and these were prevented by the cannabinoid 1 receptor but not by the cannabinoid 2 receptor antagonist. Intrathecal injection of the cannabinoid 2 receptor agonist JWH015 reversed postoperative hypersensitivity (89 +/- 5% maximum possible effect; P < 0.05), and this was reversed by the cannabinoid 2 but not by the cannabinoid 1 receptor antagonist. JWH015, which did not induce behavioral side effects, reduced paw incision induced microglial and astrocytic activation in spinal cord (P < 0.05). CONCLUSIONS: These data indicate that intrathecal administration of cannabinoid receptor agonists may provide postoperative analgesia while reducing spinal glial activation, and that selective cannabinoid 2 receptor agonists may do so without central side effects.     

Long-term use of HU210 adversely affects spermatogenesis in rats by modulating the endocannabinoid system

Recent societal acceptance of cannabinoids as recreational and therapeutic drugs has posed a potential hazard to male reproductive health. Mammals have a highly sophisticated endogenous cannabinoid (ECS) system that regulates male (and female) reproduction and exo-cannabinoids may influence it adversely. Therefore it is imperative to determine their effects on male reproduction so that men can make informed choices as to their use. Here, an animal model was used to administer HU210, a synthetic analogue of Δ9-tetrahydrocannabinol (THC) and potent cannabinoid receptor (CB) agonist to determine its effects on reproductive organ weights, spermatogenesis, testicular histology and sperm motility. Its effects on the physiological endocannabinoid system were also investigated. Spermatogenesis was markedly impaired with reductions in total sperm count after 2?weeks of exposure. Spermatogenic efficiency was depleted, and Sertoli cell number decreased as exposure time increased with seminiferous tubules showing germ cell depletion developing into atrophy in some cases. Sperm motility was also adversely affected with marked reductions from 2?weeks on. HU210 also acted on the sperm's endocannabinoid system. Long-term use of exo-cannabinoids has adverse effects on both spermatogenesis and sperm function. These findings highlight the urgent need for studies evaluating the fertility potential of male recreational drug users. HU210, a selective agonist for CB1 and CB2 cannabinoid receptors impairs spermatogenesis and sperm motility and deregulates the endocannabinoid system.     

The incidence of gonorrhoea in urban Rhodesian Black women.

The incidence of gonorrhoea in urban Black women seen in an antenatal clinic, a gynaecological clinic and a family planning clinic, was studied. Swabs taken from the urethra, endocervix and rectum were cultured by means of the Clinicult system. The overall incidence of gonorrhoea was 9.7%. In the antenatal clinic the incidence was 2%, in the gynaecological clinic it was 11% and in the family planning clinic it was 12%.     

Usefulness and problems of pre- and post-operative anesthesia evaluation clinic

A system of preoperative anesthesia evaluation clinic can provide a chance to evaluate the surgical patients effectively and to obtain an informed consent for anesthesia from the patients with their family. To organize this system effectively, communications with the doctors, nurses and comedical staffs in other departments/ sections are necessary. Postoperative anesthesia evaluation can be performed to gather information about patient satisfaction and postoperative anesthesia-related complications. This information can be used as a feedback to each anesthesiologist to improve anesthetic management. Establishment of anesthesia evaluation clinic can improve the safety and quality of anesthesia as well as efficiency of hospital management.