Receptor subtypes and signal transduction mechanisms contributing to the estrogenic attenuation of cannabinoid-induced changes in energy homeostasis.
Receptor subtypes and signal transduction mechanisms contributing to the estrogenic attenuation of cannabinoid-induced changes in energy homeostasis.
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DOI：
10.1159/000338669
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发表时间：
2013
影响因子：
4.1
通讯作者：
Wagner EJ
中科院分区：
文献类型：
--
作者：
Washburn N;Borgquist A;Wang K;Jeffery GS;Kelly MJ;Wagner EJ
我们研究了大麻素诱导的能量平衡变化的雌激素调节的受体亚型和信号转导机制。在经s.c.给药的卵巢切除雌性豚鼠中评价了摄食量，在某些情况下，还评价了O2消耗量、CO2产生量和呼吸交换率。与大麻素受体激动剂WIN 55，212 -2或其克雷美佛/乙醇/0.9%盐水载体，以及与苯甲酸雌二醇（EB）、雌激素受体（ER）α激动剂PPT、ERβ激动剂DPN、Gq偶联膜ER激动剂STX、GPR 30激动剂G-1或其各自的载体。在下丘脑切片中进行膜片钳记录。EB、STX、PPT和G-1降低了每日摄食量。其中，EB、STX和PPT在1-4小时内阻断了WIN 55，212 -2诱导的食物摄入增加。（15分钟内）减弱大麻素介导的对弓状神经元的突触输入的减少，抑制蛋白激酶C（PKC）可完全阻断此作用，抑制蛋白激酶A（PKA）则可减弱此作用。STX，而不是PPT，模仿这种快速的雌激素效应。然而，PPT消除了大麻素诱导的对24小时前处理的动物细胞中谷氨酸能神经传递的抑制。雌激素拮抗这种突触前抑制，观察到在apoxigenic POMC神经元。这些数据表明，雌激素通过涉及PKC和PKA活化的Gq偶联膜ER和ERα介导的机制负性调节大麻素诱导的能量平衡变化。因此，它们进一步加深了我们对雌激素在调节女性能量稳态中调节大麻素敏感性的途径的理解。
We examined the receptor subtypes and signal transduction mechanisms contributing to the estrogenic modulation of cannabinoid-induced changes in energy balance. Food intake and, in some cases, O2 consumption, CO2 production and the respiratory exchange ratio, were evaluated in ovariectomized female guinea pigs treated s.c. with the cannabinoid receptor agonist WIN 55,212-2 or its cremephor/ethanol/0.9% saline vehicle, and either with estradiol benzoate (EB), the estrogen receptor (ER)α agonist PPT, the ERβ agonist DPN, the Gq-coupled membrane ER agonist STX, the GPR30 agonist G-1 or their respective vehicles. Patch-clamp recordings were performed in hypothalamic slices. EB, STX, PPT and G-1 decreased daily food intake. Of these, EB, STX and PPT blocked the WIN 55,212-2-induced increase in food intake within 1-4 hr. The estrogenic diminution of cannabinoid-induced hyperphagia correlated with a rapid (within 15 min) attenuation of cannabinoid-mediated decreases in glutamatergic synaptic input onto arcuate neurons, which was completely blocked by inhibition of protein kinase C (PKC) and attenuated by inhibition of protein kinase A (PKA). STX, but not PPT, mimicked this rapid estrogenic effect. However, PPT abolished the cannabinoid-induced inhibition of glutamatergic neurotransmission in cells from animals treated 24 hr prior. The estrogenic antagonism of this presynaptic inhibition was observed in anorexigenic POMC neurons. These data reveal that estrogens negatively modulate cannabinoid-induced changes in energy balance via Gq-coupled membrane ER- and ERα-mediated mechanisms involving activation of PKC and PKA. As such, they further our understanding of the pathways through which estrogens act to temper cannabinoid sensitivity in regulating energy homeostasis in females.
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影响因子：
5
作者：
Kellert, Brian A.;Nguyen, Mike C.;Nguyen, Cara;Nguyen, Que H.;Wagner, Edward J.
通讯作者：
Wagner, Edward J.
影响因子：
5.3
作者：
Boulware, Marissa I.;Kordasiewicz, Holly;Mermelstein, Paul G.
通讯作者：
Mermelstein, Paul G.
DOI：
10.1016/s0169-328x(03)00211-0
发表时间：
2003-08-19
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Chang, A;Li, PP;Warsh, JJ
通讯作者：
Warsh, JJ
影响因子：
3.7
作者：
Farhang, Borzoo;Diaz, Shanna;Wagner, Edward J
通讯作者：
Wagner, Edward J
影响因子：
2.9
作者：
Ho, Jennie;Cox, Jeremy M.;Wagner, Edward J.
通讯作者：
Wagner, Edward J.