MECHANISM FOR SIGNAL TRANSDUCTION OF OPIOID RECEPTOR STIMULATION OF MYOCYTES

最近发现的阿片肽受体的存在， 心室细胞的功能研究 刺激这些受体产生的效应。 在这 一种天然存在的阿片肽，亮氨酸脑啡肽 （Leuenk），一种δ受体激动剂，导致细胞凋亡的显著减少。 单个成年大鼠心室肌细胞的抽搐幅度。 这种效果 在很大程度上，是由于细胞溶质的振幅减少， Ca 2+瞬变（Cai）。 Cai瞬变跟随激励 心脏细胞是由于L型肌膜钙通道的激活 导致Ca 2+通过这些通道（伊卡）流入。 这种Ca 2+流入 触发肌浆网（SR）释放Ca 2+， 含Ca 2+的SR用于后续释放。 具体机制由 这是蔡减少Leuenk已部分阐明。 洛伊恩克 导致SR中Ca 2+的释放，并导致SR中Ca 2+的减少。 SR中的Ca 2+含量。 这些影响可能归因于 Leuenk生产的IP 3和IP 4增加。 但不清楚 Leuenk是否也降低了伊卡。 在这方面， 阿片肽阻断神经递质从神经元释放， 这归因于这些细胞中Ca 2+通道电流的减少。 在本研究中，我们确定了Leuenk对伊卡的影响， 从成年大鼠新鲜分离的单个心室细胞。 采用全细胞电压钳技术，用膜片式移液管测量伊卡 模式 我们观察到Leuenk（10 ~（-7）M）降低了伊卡的幅度 在23 ℃下以0.2 Hz进行常规刺激时， 因此 Leuenk没有改变伊卡IV关系。 伊卡抑郁症 Leuenk可被特异性δ受体拮抗剂纳洛酮阻断。 伊卡失活动力学不受Leuenk影响。 那个伦克 降低伊卡的幅度表明刺激δ 阿片样物质受体导致两个减少的幅度， 触发Ca 2+释放和SR的Ca 2+负载减少。 因此，阿片肽具有减少Cai瞬变和 单个心室细胞的收缩幅度，是， 部分原因是伊卡减少。

The recent discovery of the presence of opioid peptide receptors on cardiac ventricular cells has prompted investigation of functional effects that result from stimulation of these receptors. In this regard, a naturally occurring opioid peptide, Leucine enkephalin (Leuenk), a delta receptor agonist, leads to a marked reduction in the twitch amplitude of single adult rat ventricular myocytes. This effect is due, in large part, to a reduction in the amplitude of the cytosolic Ca2+ transient (Cai). The Cai transient following the excitation of heart cells is due to activation of L-type sarcolemmal Ca2+ channels leading to Ca2+ influx via these channels (ICa). This Ca2+ influx triggers Ca2+ release from the sarcoplasm reticulum (SR) and also loads the SR with Ca2+ for subsequent releases. The specific mechanism by which Cai is reduced by Leuenk have been partly elucidated. Leuenk causes a release of Ca2+ from the SR and leads to a reduction in the amount of Ca2+ in the SR stores. These effects may be attributable to an increase in IP3 and IP4 produced by Leuenk. However, it is unknown whether Leuenk also decreases ICa. In this regard, the effect of opioid peptides to block neurotransmitters release from neurons has been attributed to a reduction in Ca2+ channel current in these cells. In the present study we determined the effect of Leuenk on ICa of individual cardiac ventricular cells freshly isolated from adult rats. ICa was measured via patch pipette in the whole cell voltage clamp mode. We observed that Leuenk (10-7M) decreases the amplitude of ICa by 40% during regular stimulation at 0.2 Hz at 23 degrees C. Thus the ICa IV relation was not altered by Leuenk. The ICa depression by Leuenk was abolished by Naloxone, a specific delta receptor antagonist. The ICa inactivation kinetics were unaffected by Leuenk. That Leuenk decreases the magnitude of ICa indicates that stimulation of delta opioid receptors leads to both a reduction in the magnitude of the trigger for Ca2+ release and to a reduction in Ca2+ loading of the SR. Thus, the opioid peptide effects to decrease the Cai transient and contraction amplitudes in individual cardiac ventricular cells, are, in part, due to a reduction in ICa.