Repeated Arterial Occlusion, Delta-Opioid Receptor (DOR) Plasticity and Vagal Transmission Within the Sinoatrial Node of the Anesthetized Dog
Repeated Arterial Occlusion, Delta-Opioid Receptor (DOR) Plasticity and Vagal Transmission Within the Sinoatrial Node of the Anesthetized Dog
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DOI：
10.3181/0808-rm-242
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发表时间：
2009-01-01
影响因子：
3.2
通讯作者：
Caffrey, James L.
中科院分区：
文献类型：
--
作者：
Deo, Shekhar H.;Barlow, Matthew A.;Caffrey, James L.
冠状动脉血流的短暂中断可以预先调节心脏，参与 δ-阿片受体 (DOR) 机制，并减少随后较长时间冠状动脉闭塞通常伴随的损害。麻醉犬的窦房结动脉反复短时间闭塞逐渐升高结节甲硫氨酸-脑啡肽-精氨酸-苯丙氨酸（MEAP），并在随后的长时间闭塞过程中改善迷走神经传导。 DOR 1 型 (DOR-1) 拮抗剂 BNTX 可逆转迷走神经效应。较高剂量的脑啡肽通过 DOR-2 机制中断迷走神经传递。目前的研究测试了迷走神经效应是否需要预处理（PC）方案、后期闭塞或两者的组合。该研究还测试了进化的迷走神经效应是否包括竞争性 DOR-2 迷走神经影响的撤销。在连续的SA结动脉闭塞期间，迷走神经传导逐渐改善。假手术动物和 DOR-1 阻断后不存在迷走神经效应。完成 PC 方案后，外源性应用 MEAP 迷走神经溶解剂量可减少正常和闭塞条件下的迷走神经传递。与对照组相比，这些 DOR-2 迷走神经溶解效应的程度较小，并且重复的 MEAP 挑战迅速进一步削弱了迷走神经溶解反应。先前的 DOR-1 阻断不会改变 PC 介导的 DOR-2 迷走神经反应的逐渐丧失。总之，DOR-1 迷走神经反应是从 PC 协议早期的信号进化而来的，而竞争性 DOR-2 迷走神经反应的侵蚀可能有助于暴露迷走神经反应。这些数据支持这样的假设：PC 和 DOR-2 刺激促进 DOR 运输，并下调迷走神经 DOR-2 表型，有利于迷走神经 DOR-1 表型。 DOR-1 阻断可能通过隔离新出现的受体来加速这一过程。实验生物医学 234:84-94, 2009
Brief interruptions in coronary blood flow precondition the heart, engage delta-opioid receptor (DOR) mechanisms and reduce the damage that typically accompanies subsequent longer coronary occlusions. Repeated short occlusions of the sinoatrial (SA) node artery progressively raised nodal methionine-enkephalin-arginine-phenylalanine (MEAP) and improved vagal transmission during subsequent long occlusions in anesthetized dogs. The DOR type-1 (DOR-1) antagonist, BNTX reversed the vagotonic effect. Higher doses of enkephalin interrupted vagal transmission through a DOR-2 mechanism. The current study tested whether the preconditioning (PC) protocol, the later occlusion or a combination of both was required for the vagotonic effect. The study also tested whether evolving vagotonic effects included withdrawal of competing DOR-2 vagolytic influences. Vagal transmission progressively improved during successive SA nodal artery occlusions. The vagotonic effect was absent in sham animals and after DOR-1 blockade. After completing the PC protocol, exogenously applied vagolytic doses of MEAP reduced vagal transmission under both normal and occluded conditions. The magnitude of these DOR-2 vagolytic effects was small compared to controls and repeated MEAP challenges rapidly eroded vagolytic responses further. Prior DOR-1 blockade did not alter the PC mediated, progressive loss of DOR-2 vagolytic responses. In conclusion, DOR-1 vagotonic responses evolved from signals earlier in the PC protocol and erosion of competing DOR-2 vagolytic responses may have contributed to an unmasking of vagotonic responses. The data support the hypothesis that PC and DOR-2 stimulation promote DOR trafficking, and down regulation of the vagolytic DOR-2 phenotype in favor of the vagotonic DOR-1 phenotype. DOR-1 blockade may accelerate the process by sequestering newly emerging receptors. Exp Biol Med 234:84-94, 2009