Sex-specific role for adenylyl cyclase type 7 in alcohol dependence.
Sex-specific role for adenylyl cyclase type 7 in alcohol dependence.
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DOI：
10.1016/j.biopsych.2011.01.037
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发表时间：
2011-06-01
影响因子：
10.6
通讯作者：
Tabakoff, Boris
中科院分区：
文献类型：
--
作者：
Desrivieres, Sylvane;Pronko, Sergey P.;Lourdusamy, Anbarasu;Ducci, Francesca;Hoffman, Paula L.;Wodarz, Norbert;Ridinger, Monika;Rietschel, Marcella;Zelenika, Diana;Lathrop, Mark;Schumann, Gunter;Tabakoff, Boris
酒精已被证明对环腺苷-3′，5′单磷酸腺苷（cAMP）信号通路具有关键调节作用。一些对cAMP信号作出反应的下游效应物（例如，蛋白激酶A， cAMP反应元件结合蛋白）反过来又被研究与饮酒的关系。然而，这些研究并没有描绘出酒精在cAMP级联中的作用可能转化为饮酒行为差异的点。为了进一步了解cAMP合成在饮酒和酒精依赖中的作用，我们研究了一种特定的腺苷酸环化酶异构体，腺苷酸环化酶（AC） 7型，它的活性被乙醇选择性地增强。我们测量了Adcy7基因一个拷贝被破坏（Adcy7+/−）的小鼠的酒精消耗和偏好。为了证明该基因与人类酒精依赖的相关性，我们在1703名酒精依赖个体和1347名对照受试者中测试了ADCY7基因多态性与酒精依赖的相关性。我们发现Adcy7+/−雌性小鼠比野生型小鼠对酒精有更高的偏好，而Adcy7+/−雄性小鼠与野生型对照小鼠在酒精消耗或偏好方面几乎没有差异。在人类样本中，我们发现ADCY7的单核苷酸多态性与女性酒精依赖有关，这些标记也与ADCY7的表达（信使RNA）水平有关。这些发现暗示7型腺苷酸环化酶是导致饮酒和酒精依赖发展的分子途径的关键组成部分。
Alcohol has been shown to critically modulate cyclic adenosine-3′,5′ monophosphate (cAMP) signaling. A number of downstream effectors that respond to the cAMP signals (e.g., protein kinase A, cAMP response element binding protein) have, in turn, been examined in relation to alcohol consumption. These studies did not, however, delineate the point at which the actions of alcohol on the cAMP cascade might translate into differences in drinking behavior. To further understand the role of cAMP synthesis in alcohol drinking and dependence, we investigated a specific adenylyl cyclase isoform, adenylyl cyclase (AC) Type 7, whose activity is selectively enhanced by ethanol. We measured alcohol consumption and preference in mice in which one copy of the Adcy7 gene was disrupted (Adcy7+/−). To demonstrate relevance of this gene for alcohol dependence in humans, we tested the association of polymorphisms in the ADCY7 gene with alcohol dependence in a sample of 1703 alcohol-dependent individuals and 1347 control subjects. We show that Adcy7+/− female mice have higher preference for alcohol than wild-type mice, whereas there is little difference in alcohol consumption or preference between Adcy7+/− male mice and wild-type control subjects. In the human sample, we found that single nucleotide polymorphisms in ADCY7 associate with alcohol dependence in women, and these markers are also associated with ADCY7 expression (messenger RNA) levels. These findings implicate adenylyl cyclase Type 7 as a critical component of the molecular pathways contributing to alcohol drinking and the development of alcohol dependence.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
DOI：
10.1111/j.1530-0277.2006.00096.x
发表时间：
2006-05-01
影响因子：
3.2
作者：
Ferraro, FM;Sparta, DR;Thiele, TE
通讯作者：
Thiele, TE
影响因子：
3.9
作者：
Lachner, G;Wittchen, HU;Pfister, H
通讯作者：
Pfister, H
影响因子：
11
作者：
Comings, DE;Muhleman, D;MacMurray, JP
通讯作者：
MacMurray, JP
影响因子：
4.4
作者：
FAGERSTROM, KO
通讯作者：
FAGERSTROM, KO