Modulation of the exocytotic and carrier-mediated transmitter release by endogenous and exogenously added cannabinoids

内源性和外源性添加大麻素对胞吐和载体介导的递质释放的调节

• 批准号: 62830195
• 负责人: Professor Dr. Eberhard Schlicker
• 金额: --
• 依托单位: Institut für Pharmakologie und Toxikologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/62830195?language=en
• 关键词: Modulation; exocytotic; carrier; mediated; transmitter

Cannabinoid CB1 receptors inhibit the action potential-driven, exocytotic transmitter release in neurons. Rimonabant, an inverse CB1 agonist, facilitates transmitter release, probably due to interruption of an endogenous tone built up by endocannabinoids like anandamide and/or 2-arachidonoylglycerol. Their role shall be clarified by determination of transmitter release in hippocampal slices (i) exposed to inhibitors of the synthesis and degradation of either endocannabinoid or (ii) obtained from mice not expressing such enzymes. The facilitatory effect of rimonabant might also be due to the fact that the CB1 receptors are constitutively active. This shall be checked by comparing the effect of an inverse agonist and neutral antagonist at CB1 receptors on transmitter release in isolated tissues and in cells. Finally, there is almost no information as to whether CB1 receptors affect the non-exocytotic glutamate release caused by hypoxia. The occurrence of such receptors and a possible endogenous tone shall be studied in hippocampal slices from wild type mice and mice not expressing CB1 receptors or endocannabinoid-synthesizing or -degrading enzymes. The findings may contribute to a better understanding of the clinical effect of rimonabant and of the possible use of CB1 agonists as neuroprotective drugs.

大麻素CB 1受体抑制神经元中动作电位驱动的胞吐递质释放。利莫那班是一种反向CB 1激动剂，促进递质释放，可能是由于内源性大麻素如大麻素和/或2-花生四烯酸甘油建立的内源性音调中断。应通过测定海马切片（i）暴露于内源性大麻素合成和降解抑制剂或（ii）从不表达此类酶的小鼠中获得的海马切片中的递质释放来阐明其作用。利莫那班的易化作用也可能是由于CB 1受体具有组成性活性。这应通过比较CB 1受体的反向激动剂和中性拮抗剂对分离组织和细胞中递质释放的影响来检查。最后，几乎没有关于CB 1受体是否影响由缺氧引起的非胞吐性谷氨酸释放的信息。应在野生型小鼠和不表达CB 1受体或内源性大麻素合成或降解酶的小鼠的海马切片中研究此类受体的发生和可能的内源性张力。这些发现可能有助于更好地了解利莫那班的临床效果和CB 1激动剂作为神经保护药物的可能用途。

项目成果

Involvement of central β2-adrenergic, NMDA and thromboxane A2 receptors in the pressor effect of anandamide in rats

• DOI: 10.1007/s00210-010-0497-6
• 发表时间: 2010-04-01
• 期刊: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
• 影响因子: 3.6
• 作者: Malinowska, B.;Zakrzeska, A.;Schlicker, E.
• 通讯作者: Schlicker, E.

Prostaglandins of the E series inhibit monoamine release via EP3 receptors: proof with the competitive EP3 receptor antagonist L-826,266

• DOI: 10.1007/s00210-009-0478-9
• 发表时间: 2010-01-01
• 期刊: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
• 影响因子: 3.6
• 作者: Guenther, J.;Schulte, K.;Schlicker, E.
• 通讯作者: Schlicker, E.

Cannabinoid CB1 receptor activation, pharmacological blockade, or genetic ablation affects the function of the muscarinic auto- and heteroreceptor

大麻素 CB1 受体激活、药理学阻断或基因消除会影响毒蕈碱自身和异源受体的功能

• DOI: 10.1007/s00210-011-0717-8
• 发表时间: 2012
• 期刊: Naunyn-Schmiedeberg's Archives of Pharmacology
• 作者: Schulte K;Steingrüber N;Jergas B;Redmer A;Kurz CM;Buchalla R;Lutz B;Zimmer A;Schlicker E
• 通讯作者: Schlicker E

Acute myocardial ischemia enhances the vanilloid TRPV1 and serotonin 5-HT_3 receptor-mediated Bezold-Jarisch reflex in rats

急性心肌缺血增强大鼠香草醛 TRPV1 和血清素 5-HT_3 受体介导的 Bezold-Jarisch 反射

• DOI: 10.1016/s1734-1140(11)70709-5
• 发表时间: 2012
• 期刊: Pharmacological Reports
• 影响因子: 4.4
• 作者: Łupiński SŁ;Schlicker E;Pędzińska-Betiuk A;Malinowska B
• 通讯作者: Malinowska B

Urethane, but not pentobarbitone, attenuates presynaptic receptor function in rats: a contribution to the choice of anaesthetic

• DOI: 10.1111/j.1476-5381.2009.00315.x
• 发表时间: 2009-08-01
• 期刊: BRITISH JOURNAL OF PHARMACOLOGY
• 影响因子: 7.3
• 作者: Kurz, C. M.;Baranowska, U.;Schlicker, E.
• 通讯作者: Schlicker, E.