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儿茶酚胺类激动剂激活小鼠视交叉上核永生神经元细胞的转录活性。

Adrenergic Agonists Activate Transcriptional Activity in Immortalized Neuronal Cells From the Mouse Suprachiasmatic Nucleus.

机构信息

Institute for Anatomy II, Goethe University Frankfurt, Frankfurt, Germany.

Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.

出版信息

J Pineal Res. 2024 Aug;76(5):e12999. doi: 10.1111/jpi.12999.

Abstract

The suprachiasmatic nucleus of the hypothalamus (SCN) houses the central circadian oscillator of mammals. The main neurotransmitters produced in the SCN are γ-amino-butyric acid, arginine-vasopressin (AVP), vasoactive intestinal peptide (VIP), pituitary-derived adenylate cyclase-activating peptide (PACAP), prokineticin 2, neuromedin S, and gastrin-releasing peptide (GRP). Apart from these, catecholamines and their receptors were detected in the SCN as well. In this study, we confirmed the presence of β-adrenergic receptors in SCN and a mouse SCN-derived immortalized cell line by immunohistochemical, immuno-cytochemical, and pharmacological techniques. We then characterized the effects of β-adrenergic agonists and antagonists on cAMP-regulated element (CRE) signaling. Moreover, we investigated the interaction of β-adrenergic signaling with substances influencing parallel signaling pathways. Our findings have potential implications on the role of stress (elevated adrenaline) on the biological clock and may explain some of the side effects of β-blockers applied as anti-hypertensive drugs.

摘要

下丘脑的视交叉上核(SCN)是哺乳动物中央生物钟的所在地。SCN 中产生的主要神经递质是γ-氨基丁酸、精氨酸加压素(AVP)、血管活性肠肽(VIP)、垂体衍生的腺苷酸环化酶激活肽(PACAP)、促动力素 2、神经调节素 S 和胃泌素释放肽(GRP)。除此之外,SCN 中还检测到儿茶酚胺及其受体。在这项研究中,我们通过免疫组织化学、免疫细胞化学和药理学技术证实了 SCN 中β-肾上腺素能受体的存在以及源自小鼠 SCN 的永生化细胞系。然后,我们研究了β-肾上腺素能激动剂和拮抗剂对 cAMP 调节元件(CRE)信号的影响。此外,我们研究了β-肾上腺素能信号与影响平行信号通路的物质之间的相互作用。我们的发现可能对压力(肾上腺素升高)对生物钟的作用具有重要意义,并可能解释一些作为抗高血压药物应用的β-阻滞剂的副作用。

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