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: 3789800
• 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/3789800
• 关键词: beta adrenergic receptor; beta antiadrenergic agent; calcium channel; calcium indicator; catecholamine inhibitor; electrophysiology; enkephalins; heart cell; heart contraction; heart pharmacology; laboratory rat; leucine; myocardium; naloxone; nerve endings; norepinephrine; opioid receptor; sarcolemma; single cell analysis; stimulant /agonist; stress; synapses; 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 isolated rat ventricular myocytes (electrically stimulated at 0.5 Hz at 23 degrees C) demonstrate that the increase in cytosolic Ca2+ transient (indexed by indo-1 fluorescence) and contraction (measured via photodiode array) amplitudes and increase in the sarcolemmal L type Ca2+ current ICa) 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 delta OP receptors on heart cells can "short circuit" the BAR mediated response and may protect against cell Ca2+ overload during stress.

最近从这个实验室报道，阿片受体存在于 心肌膜，阿片类激动剂具有负性变力作用 对心脏的影响。在完整的动物和隔离的心脏中，阿片类药物 激动剂抑制神经末梢的去甲肾上腺素释放。然而，无论是 刺激心肌阿片(OP)受体可改变对 突触后水平的β-肾上腺素能受体(BAR)刺激 未知。我们对单个分离的大鼠心室肌细胞的研究 (在23摄氏度下以0.5赫兹电刺激)表明 细胞内钙瞬变增加(以Indo-1荧光为指标)和 收缩(通过光电二极管阵列测量)幅度和增加 肌膜L型钙电流对去甲肾上腺素(NE，10- 7M)通过加入10-8M亮氨酸脑啡肽(LE)而取消，a 三角洲行动激动剂。纳洛酮(Nal，10-8M)可逆转LE效应。 因此，刺激心脏细胞上的DeltaOP受体可以“短路”。 BAR介导的反应可能对细胞内钙超载有保护作用 在压力下。