'Cross talk' between opioid peptide and adrenergic receptor signaling in isolated rat heart.
'Cross talk' between opioid peptide and adrenergic receptor signaling in isolated rat heart.
复制标题
离体大鼠心脏中阿片肽和肾上腺素能受体信号传导之间的“串扰”。
DOI：
10.1161/01.cir.95.8.2122
复制
发表时间：
1997
期刊：
影响因子：
37.8
通讯作者：
Lakatta,EG
中科院分区：
文献类型：
--
作者：
Pepe,S;Xiao,RP;Hohl,C;Altschuld,R;Lakatta,EG
背景心肌细胞膜含有儿茶酚胺和阿片肽受体。阿片肽与心脏神经末梢的儿茶酚胺共同释放。我们研究了OPR刺激是否会影响β-肾上腺素能受体（β-AR）刺激在离体等容大鼠心脏中的作用，以及这种相互作用的机制是否涉及β-AR亚型或β-AR介导的cAMP增加的改变。方法和结果与对照组相比，去甲肾上腺素（NE，10− 7 mol/L）使左心室收缩压峰值（LVSP）和cAMP增加两倍以上。δ-OPR激动剂亮氨酸脑啡肽（LE，10− 8 mol/L）可显著抑制β1-AR诱导的正性肌力作用和cAMP水平的升高，但单独使用对基础LVSP和基础cAMP水平无影响。在LE+NE灌流液中加入OPR拮抗剂纳洛酮10− 8 mol/L可逆转LE引起的cAMP和LVSP的降低，尽管纳洛酮单独对LVSP和cAMP水平无影响。LE不能抵消不可降解cAMP类似物CPTcAMP 2.3×10− 5 mol/L或高浓度forskolin（10− 7 mol/L）引起的LVSP的两倍增加，但可以逆转10− 8和0.5×10− 8 mol/L forskolin引起的LVSP分别增加173±11.8%和135±13.6%。LE在所有浓度（10−7、10−8和0.5×10− 8 mol/L）的毛喉素下都抑制cAMP的产生。百日咳毒素（PTX）预处理可阻断LE对β1-AR刺激的作用。Zinterol 10 - 5和10 - 6 mol/L是一种特异性β2-AR激动剂，在大鼠心脏中产生cAMP非依赖性变力作用，导致LVSP增加225±14%和182±5%，并且不能被LE逆转。结论δ-OPR和β1-AR信号通路之间的有效抑制性“串扰”通过PTX敏感的Gi/o蛋白参与大鼠心脏腺苷酸环化酶抑制。
BackgroundCardiac myocyte sarcolemma contains both catecholamine and opioid peptide receptors (OPRs). Opioid peptides are coreleased with catecholamines from nerve terminals in the heart. We investigated whether OPR stimulation influences the effects of β-adrenergic receptor (β-AR) stimulation in the isolated, isovolumic rat heart and whether the mechanism of such an interaction involves both β-AR subtypes or an alteration in β-AR–mediated increase in cAMP.Methods and ResultsNorepinephrine (NE, 10−7mol/L) increased peak left ventricular systolic pressure (LVSP) and cAMP more than twofold compared with controls. The δ-OPR agonist leucine-enkephalin (LE, 10−8mol/L) markedly inhibited the β1-AR–induced positive inotropic effect and increase in cAMP but alone had no effect on basal LVSP or basal cAMP levels. The OPR antagonist naloxone 10−8mol/L added to LE+NE perfusate reversed the LE-induced decrease in cAMP and LVSP even though naloxone alone had no effect on LVSP and cAMP levels. LE could not counteract the twofold increase in LVSP produced by the nondegradable cAMP analog CPTcAMP 2.3×10−5mol/L or a high concentration of forskolin (10−7mol/L) but did reverse the 173±11.8% and 135±13.6% increases in LVSP stimulated by 10−8and 0.5×10−8mol/L forskolin, respectively. LE inhibited cAMP production at all concentrations of forskolin (10−7, 10−8, and 0.5×10−8mol/L). Pertussis toxin (PTX) pretreatment abolished LE effects on β1-AR stimulation. Zinterol 10−5and 10−6mol/L, a specific β2-AR agonist that elicits a cAMP-independent inotropic effect in rat heart, caused 225±14% and 182±5% increases in LVSP that could not be reversed by addition of LE.ConclusionsPotent, inhibitory “cross talk” between δ-OPR and β1-AR signaling pathways occurs via a PTX-sensitive Gi/oprotein involved in adenylyl cyclase inhibition in rat heart.