MECHANISM FOR SIGNAL TRANSDUCTION OF OPIOID RECEPTOR STIMULATION OF MYOCYTES

阿片肽受体存在的最新研究进展 心肌细胞促进了对功能影响的研究 这是由这些受体的刺激产生的。在这方面，a 天然阿片肽，亮氨酸脑啡肽(Leuenk)，一种 受体激动剂可显著降低大鼠心肌细胞的抽动幅度 单个成年大鼠心肌细胞。这种影响在很大程度上是由于， 导致胞浆钙瞬变(CaI)幅度降低。 心肌细胞兴奋后的CAI瞬变是由于 L型肌膜钙通道激活导致钙内流 这些频道(ICA)。这种钙离子内流触发了细胞内钙离子的释放 肌浆网(SR)，也向SR加载钙离子，以供后续 发布。Leuenk还原CaI的具体机制有 已被部分阐明。Leuenk引起SR的钙释放，并 导致SR储备物中的钙离子含量减少。这些 影响可能归因于由 莱昂克。然而，目前尚不清楚Leuenk是否也会降低ICA。在……里面 对此，阿片肽阻断神经递质的作用 神经元的释放归因于钙通道的减少 这些细胞中的电流。在目前的研究中，我们确定了 Leuenk对新鲜分离的单个心肌细胞ICa的影响 从成年大鼠身上。通过膜片移液管在整个细胞内测量ICA 电压钳位模式。我们观察到，Leuenk(10-7M)降低了 23度0.2赫兹常规刺激时ICA波幅增加40% 因此，Leuenk没有改变ICA IV关系。ICA 特异性K受体纳洛酮可消除Leuenk所致的抑郁 对抗者。Leuenk对ICA失活动力学无影响。 Leuenk降低ICA的幅度表明，刺激 德尔塔阿片受体导致两种程度的降低 触发Ca~(2+)释放和SR的Ca~(2+)负荷减少。 因此，阿片肽具有降低CAI一过性和 单个心肌细胞的收缩幅度，在 部分，由于ICA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.