the role of phosphatidylinositol-3-kinase and amp-activated kinase in the rapid estrogenic attenuation of cannabinoid-induced changes in energy homeostasisphosphatidylinositol-3-kinase的作用,活化激酶cannabinoid-induced雌激素的快速衰减的能量体内平衡的变化.pdfVIP

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the role of phosphatidylinositol-3-kinase and amp-activated kinase in the rapid estrogenic attenuation of cannabinoid-induced changes in energy homeostasisphosphatidylinositol-3-kinase的作用,活化激酶cannabinoid-induced雌激素的快速衰减的能量体内平衡的变化.pdf

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the role of phosphatidylinositol-3-kinase and amp-activated kinase in the rapid estrogenic attenuation of cannabinoid-induced changes in energy homeostasisphosphatidylinositol-3-kinase的作用,活化激酶cannabinoid-induced雌激素的快速衰减的能量体内平衡的变化

Pharmaceuticals 2011, 4, 630-651; doi:10.3390/ph4040630 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Article The Role of Phosphatidylinositol-3-Kinase and AMP-Activated Kinase in the Rapid Estrogenic Attenuation of Cannabinoid-Induced Changes in Energy Homeostasis Garrett S. Jeffery, Kelly C. Peng and Edward J. Wagner * Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA * Author to whom correspondence should be addressed; E-Mail: EWagner@. Received: 7 March 2011; in revised form: 31 March 2011/ Accepted: 4 April 2011 / Published: 12 April 2011 Abstract: We sought to determine the involvement of phosphatidyl inositol 3-kinase (PI3K) and AMP-activated protein kinase (AMPK) in the estrogenic antagonism of the cannabinoid regulation of energy homeostasis. Food intake and body weight were evaluated in ovariectomized female guinea pigs treated s.c. with estradiol benzoate (EB) or its sesame oil vehicle, or the CB1 receptor antagonist AM251 or its cremephor/ethanol/0.9% saline vehicle. AMPK catalytic subunit, PI3K p85α regulatory subunit and proopiomelanocortin (POMC) gene expression was assessed via quantitative RT-PCR in microdissected hypothalamic tissue. Whole-cell patch clamp recordings were performed in hypothalamic slices. Both EB and AM251 decreased food intake and weight gain, and increased AMPKα1, AMPKα2 and PI3K p85α gene expression in the mediobasal hypothalamus. 17β-Estradiol rapidly and markedly attenua