Estrogen rapidly attenuates cannabinoid-induced changes in energy homeostasis.
Estrogen rapidly attenuates cannabinoid-induced changes in energy homeostasis.
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DOI：
10.1016/j.ejphar.2009.09.001
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发表时间：
2009-11-10
影响因子：
5
通讯作者：
Wagner, Edward J.
中科院分区：
文献类型：
--
作者：
Kellert, Brian A.;Nguyen, Mike C.;Nguyen, Cara;Nguyen, Que H.;Wagner, Edward J.
我们研究了雌激素是否对大麻素诱导的食物摄入、核心体温和阿黑皮素原（POMC）突触神经传递的调节产生负调节作用。在腹部植入热数据记录器并经s.c.处理的卵巢切除雌性豚鼠中评价摄食量。与大麻素CB 1/CB 2受体激动剂WIN 55，212 -2、CB 1受体拮抗剂AM 251或它们的克列灭佛/乙醇/0.9%盐水载体，以及与苯甲酸雌二醇（EB）或其芝麻油载体。通过弓状核切片进行全细胞膜片钳记录。WIN 55，212 -2导致食物摄入量呈剂量和时间依赖性增加。EB在给药后8-24 h减少摄食量，但迅速完全阻断WIN 55，212 -2引起的摄食量增加。EB还减弱了WIN 55，212 -2诱导的核心体温降低。AM 251诱导的摄食量减少未受影响。由EB引起的WIN 55，212 -2诱导的食物摄入增加的减少与类固醇应用10-15分钟内发生的大麻素受体介导的多巴胺能微型兴奋性突触后电流频率的显著减弱相关。此外，EB完全阻断了由WIN 55，212 -2引起的A型K+电流失活曲线的去极化偏移。EB介导的，生理拮抗这些突触前和突触后的行动引起大麻素受体活化弓形神经元免疫阳性的POMC神经元的表型标志物中观察到。这些数据表明，雌激素负调节大麻素诱导的食欲，体温和POMC神经元活动的变化。他们还传授洞察神经解剖基板和效应器系统后，这些反调节因子收敛在控制能量稳态。
We examined whether estrogen negatively modulates cannabinoid-induced regulation of food intake, core body temperature and neurotransmission at proopiomelanocortin (POMC) synapses. Food intake was evaluated in ovariectomized female guinea pigs abdominally implanted with thermal DataLoggers and treated s.c. with the cannabinoid CB1/CB2 receptor agonist WIN 55,212-2, the CB1 receptor antagonist AM251 or their cremephor/ethanol/0.9% saline vehicle, and with estradiol benzoate (EB) or its sesame oil vehicle. Whole-cell patch clamp recordings were performed in slices through the arcuate nucleus. WIN 55,212-2 produced dose- and time-dependent increases in food intake. EB decreased food intake 8–24 h after administration, but rapidly and completely blocked the increase in consumption caused by WIN 55,212-2. EB also attenuated the WIN 55,212-2-induced decrease in core body temperature. The AM251-induced decrease in food intake was unaffected. The diminution of the WIN 55,212-2-induced increase in food intake caused by EB correlated with a marked attenuation of cannabinoid receptor-mediated decreases in glutamatergic miniature excitatory postsynaptic current frequency occurring within 10–15 minutes of steroid application. Furthermore, EB completely blocked the depolarizing shift in the inactivation curve for the A-type K+ current caused by WIN 55,212-2. The EB-mediated, physiologic antagonism of these presynaptic and postsynaptic actions elicited upon cannabinoid receptor activation was observed in arcuate neurons immunopositive for phenotypic markers of POMC neurons. These data reveal that estrogens negatively modulate cannabinoid-induced changes in appetite, body temperature and POMC neuronal activity. They also impart insight into the neuroanatomical substrates and effector systems upon which these counter-regulatory factors converge in the control of energy homeostasis.
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