MECHANISM FOR SIGNAL TRANSDUCTION OF OPIOID RECEPTOR STIMULATION OF MYOCYTES

最近发现的阿片肽受体的存在， 心脏心室细胞的功能影响的研究 由这些受体的刺激引起的。 在这方面， 天然阿片肽，亮氨酸脑啡肽（Leuenk），一种δ 受体激动剂，导致抽搐幅度显着减少， 单个成年大鼠心室肌细胞。 这种影响在很大程度上是由于， 降低胞质Ca 2+瞬变（Cai）的幅度。 心脏细胞兴奋后的Cai瞬变是由于 激活L型肌膜Ca 2+通道，导致Ca 2+内流 这些通道（伊卡）。 这种Ca 2+内流触发Ca 2+从细胞中释放， 肌浆网（SR），并也加载SR与Ca 2+，用于随后的 释放。 Leuenk还原Cai的具体机制有 已部分澄清。 Leuenk导致SR中释放Ca 2+， 导致SR存储中的Ca 2+的量减少。 这些 影响可能是由于增加IP 3和IP 4产生的 伦克 然而，尚不清楚Leuenk是否也会降低伊卡。 在 在这方面，阿片肽阻断神经递质的作用 从神经元的释放归因于Ca 2+通道的减少 这些细胞中的电流。 在本研究中，我们确定了 Leuenk对新鲜分离的单个心室肌细胞伊卡的影响 成年大鼠。 通过贴片移液管测量全细胞中的伊卡 电压箝位模式。 我们观察到Leuenk（10- 7 M）降低了 在23度，0.2 Hz的常规刺激期间，伊卡振幅增加40% C. 因此，Leuenk没有改变伊卡IV关系。 的伊卡 Leuenk的抑制作用可被纳洛酮（一种特异性K受体）消除 拮抗剂 伊卡失活动力学不受Leuenk影响。 Leuenk降低了伊卡的大小，表明刺激 δ阿片受体既能降低 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 在单个心室细胞中的收缩幅度， 部分原因是由于伊卡的减少。

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 degree C. Thus the ICa IV relation was not altered by Leuenk. The ICa depression by Leuenk was abolished by Naloxone, a specific k 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.