室旁核中的黑皮质素4受体调节大鼠的脂肪传入反射。
Melanocortin 4 receptors in the paraventricular nucleus modulate the adipose afferent reflex in rat.
作者信息
Li Peng, Sun Hai-Jian, Zhang Ling-Li, Ding Lei, Han Ying, Zhu Guo-Qing, Zhou Ye-Bo
机构信息
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, China ; Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
出版信息
PLoS One. 2013 Nov 11;8(11):e80295. doi: 10.1371/journal.pone.0080295. eCollection 2013.
BACKGROUND AND AIM
Paraventricular nucleus (PVN) of hypothalamus is an important central component in modulating adipose afferent reflex (AAR). Melanocortin receptors (MC3/4Rs) expressions are found in the hypothalamic PVN. This study was designed to determine the roles of MC3/4Rs in the PVN in modulating the AAR and its downstream signaling pathway in normal rats.
METHODOLOGY/PRINCIPAL FINDINGS: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats. AAR was evaluated using RSNA and MAP responses to capsaicin injection into the inguinal white adipose tissue (iWAT). Microinjection of the MC3/4R agonist melanotan II (MTII) into the PVN enhanced the AAR. The MC3/4R antagonist SHU9119 or MC4R antagonist HS024 attenuated the AAR and abolished MTII-induced AAR response. The adenylate cyclase (AC) inhibitor SQ22536 or the protein kinase A (PKA) inhibitor Rp-cAMP attenuated the AAR and the effect of MTII on the AAR was abolished by pretreatment with SQ22536 or Rp-cAMP in the PVN. Furthermore, both PVN microinjection of MTII and iWAT injection of capsaicin increased the cAMP level in the PVN. SHU9119 in the PVN abolished the increase in cAMP level which induced by iWAT injection of capsaicin.
CONCLUSION
The activation of MC4Rs rather than MC3Rs enhances the AAR, and a cAMP-PKA pathway is involved in the effects of MC4Rs in the PVN.
背景与目的
下丘脑室旁核（PVN）是调节脂肪传入反射（AAR）的重要中枢组成部分。在下丘脑PVN中发现了黑皮质素受体（MC3/4Rs）的表达。本研究旨在确定PVN中MC3/4Rs在调节正常大鼠AAR及其下游信号通路中的作用。
方法/主要发现：在麻醉大鼠中记录肾交感神经活动（RSNA）和平均动脉压（MAP）。使用RSNA和MAP对向腹股沟白色脂肪组织（iWAT）注射辣椒素的反应来评估AAR。向PVN微量注射MC3/4R激动剂黑素皮质素II（MTII）可增强AAR。MC3/4R拮抗剂SHU9119或MC4R拮抗剂HS024减弱了AAR，并消除了MTII诱导的AAR反应。腺苷酸环化酶（AC）抑制剂SQ22536或蛋白激酶A（PKA）抑制剂Rp-cAMP减弱了AAR，并且在PVN中用SQ22536或Rp-cAMP预处理消除了MTII对AAR的作用。此外，PVN微量注射MTII和iWAT注射辣椒素均增加了PVN中的cAMP水平。PVN中的SHU9119消除了iWAT注射辣椒素诱导的cAMP水平升高。
结论
MC4Rs而非MC3Rs的激活增强了AAR，并且cAMP-PKA途径参与了PVN中MC4Rs的作用。
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