INTERACTION OF SIGMA OPIOID AND BETA ADRENERGIC RECEPTORS IN CARDIAC MYOCYTES

心肌细胞中西格玛阿片类药物和β肾上腺素能受体的相互作用

• 批准号: 3802250
• 负责人: R P XIAO
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3802250
• 关键词: aging; beta adrenergic receptor; beta antiadrenergic agent; calcium transporting ATPase; electrophysiology; enkephalins; fluorescent dye /probe; heart cell; heart contraction; heart pharmacology; laboratory rat; leucine; myocardium; naloxone; neuropeptide receptor; norepinephrine; sarcolemma; single cell analysis; stimulant /agonist; stress; tissue /cell culture

It has been recently reported from this lab that opioid receptors exist in myocardial membranes, and that opioid agonists have negative inotropic effects in the heart. In intact animals and in the isolated heart, opioid agonists inhibit NE release from neuron endings. However, whether stimulation of myocardial opioid (OP) receptors modifies the response to beta-adrenergic receptor (BAR) stimulation at postsynaptic levels is unknown. Our studies in individual rat ventricular myocytes (electrically stimulated at 0.5 Hz at 23 degrees C) demonstrate that the increase in cytosolic Ca 2+ transient (indexed by indo-1 fluorescence) and contraction (measured via photodiode array amplitudes and increase in the sarcolemmal L type Ca 2+ current I Ca) in response to norepinephrine (NE, 10 -7M) are abolished by the addition of 10 -8M Leucine enkephalin (LE), a delta OP agonist. The LE effect was reversed by Naloxone (Nal, 10 -8M). Thus, stimulation of the delta OP receptors on heart cells can "short circuit" the BAR mediated response and may protect against cell Ca 2+ overload during stress.

该实验室最近报道，阿片受体存在于 阿片类激动剂具有负性肌力作用， 在心脏的影响。 在完整动物和离体心脏中，阿片类药物 激动剂抑制NE从神经元末梢释放。 但无论 刺激心肌阿片样物质（OP）受体改变了对 β-肾上腺素能受体（BAR）在突触后水平的刺激是 未知 我们的研究在个别大鼠心室肌细胞（电 在23摄氏度下以0.5 Hz刺激）表明， 胞浆Ca 2+瞬变（indo-1荧光标记）和收缩 （通过光电二极管阵列振幅和肌膜增加测量） 去甲肾上腺素（NE，10 - 7 M）对L型钙电流的影响 通过添加10 - 8 M亮氨酸脑啡肽（LE）消除， 激动剂 纳洛酮（Nal，10 - 8 M）可逆转LE效应。 因此，在本发明中， 刺激心脏细胞上的δ OP受体可以“短路” BAR介导的反应并可能防止细胞Ca 2+超载 在压力下。