Octopamine Receptors from the Barnacle Balanus improvisus Are Activated by the α2-Adrenoceptor Agonist Medetomidine
Octopamine Receptors from the Barnacle Balanus improvisus Are Activated by the α2-Adrenoceptor Agonist Medetomidine
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DOI：
10.1124/mol.110.063594
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发表时间：
2010-08-01
影响因子：
3.6
通讯作者：
Blomberg, Anders
中科院分区：
文献类型：
--
作者：
Lind, Ulrika;Rosenblad, Magnus Alm;Blomberg, Anders
昆虫和其他无脊椎动物的 G 蛋白偶联章鱼胺受体代表脊椎动物中肾上腺素受体的对应物。 α(2)-肾上腺素受体激动剂美托咪定在临床上用作兽医镇静剂，被发现可以抑制藤壶的沉降过程，这是甲壳类动物个体发育的重要一步。藤壶沉积在船体上会导致生物污垢，从而产生许多有害的实际后果，美托咪定目前正在开发作为一种新型防污剂。我们现在报道，美托咪定会诱导藤壶幼虫过度活跃，从而破坏沉降过程。为了确定美托咪定的分子靶点，我们从藤壶 Balanus improvisus 中克隆了 5 个章鱼胺受体。我们通过系统发育分析表明，一种受体（BiOct α）属于α-肾上腺素受体样亚家族，其他四种（BiOct beta-R1、BiOct beta-R2、BiOct beta-R3 和 BiOct beta-R4）属于β-肾上腺素受体样章鱼胺受体亚家族。系统发育分析还表明，B. improvisus 具有与昆虫不同的 β-肾上腺素受体样章鱼胺受体。当在 CHO 细胞中表达时，克隆的受体被章鱼胺和美托咪定激活，导致细胞内 cAMP 或钙水平增加。酪胺激活受体，但效力比章鱼胺低得多。酪胺和章鱼胺之间受体区分的假设是从同源三维模型产生的。 B. improvisus octopamine 受体的表征对于更好地了解甲壳类动物中这些受体的功能以及开发环境可持续防污剂的实际应用非常重要。
G protein-coupled octopamine receptors of insects and other invertebrates represent counterparts of adrenoceptors in vertebrate animals. The alpha(2)-adrenoceptor agonist medetomidine, which is in clinical use as a veterinary sedative agent, was discovered to inhibit the settling process of barnacles, an important step in the ontogeny of this crustacean species. Settling of barnacles onto ship hulls leads to biofouling that has many harmful practical consequences, and medetomidine is currently under development as a novel type of antifouling agent. We now report that medetomidine induces hyperactivity in the barnacle larvae to disrupt the settling process. To identify the molecular targets of medetomidine, we cloned five octopamine receptors from the barnacle Balanus improvisus. We show by phylogenetic analyses that one receptor (BiOct alpha) belongs to the alpha-adrenoceptor-like subfamily, and the other four (BiOct beta-R1, BiOct beta-R2, BiOct beta-R3, and BiOct beta-R4) belong to the beta-adrenoceptor-like octopamine receptor subfamily. Phylogenetic analyses also indicated that B. improvisus has a different repertoire of beta-adrenoceptor-like octopamine receptors than insects. When expressed in CHO cells, the cloned receptors were activated by both octopamine and medetomidine, resulting in increased intracellular cAMP or calcium levels. Tyramine activated the receptors but with much lesser potency than octopamine. A hypothesis for receptor discrimination between tyramine and octopamine was generated from a homology three-dimensional model. The characterization of B. improvisus octopamine receptors is important for a better functional understanding of these receptors in crustaceans as well as for practical applications in development of environmentally sustainable antifouling agents.