Eiden L E, Ruth J A
Peptides. 1982 May-Jun;3(3):475-8. doi: 10.1016/0196-9781(82)90110-3.
Potential interactions between opiate peptides and catecholamines in mammalian heart were examined using isolated spontaneously beating rat atria as a test system. Methionine-enkephalin (ME), leucine-enkephalin (LE), phe-met-arg-phe amide (FMRFamide), D-ala2, N-methyl-phe4, met (O)5-ol-enkephalin (FK 33-834), methionine-enkephalin arg6 arg7 (ME arg6 arg7) and beta-endorphin had no effect on basal beating rate of isolated atria at all concentrations up to 10(-5) M. The positive chronotropic effect of norepinephrine (NE) on atrial rate is, however, significantly attenuated by enkephalin peptides. Thus, the maximal chronotropic effect of NE (an increase from 317 +/- 7.0 to 473 +/- 7.3 beats per minute (bpm) in 250 gm rats at a dose of 10(-5)M NE) is decreased by 42% in the presence of 10(-7)m ME. The action of ME is completely blocked by addition of 10(-7)M naloxone, which by itself has no effect on NE-induced positive chronotropy or basal beating rate. The dose-effect curve for ME attenuation of NE-induced positive chronotropy is bell-shaped, i.e., both 10(-8) M and 10(-5) M ME have no significant effect on NE positive chronotropy. Other enkephalin peptides acted in a similar manner to ME; LE (10(-7) M) and FK 33-834 (10(-8) M) decreased maximal NE-induced positive chronotropy 42 and 27%, respectively. The molluscan cardioexcitatory peptide FMRFamide (10(-7) M) also decreased maximal NE positive chronotropy, about 30%. In contrast, beta-endorphin did not significantly affect NE stimulation of atrial rate. We conclude that enkephalins can modulate the noradrenergic responsiveness of rat atria in vitro. The possible physiological relevance of this interaction is discussed.
利用离体自发搏动的大鼠心房作为测试系统，研究了阿片肽与儿茶酚胺在哺乳动物心脏中的潜在相互作用。甲硫氨酸脑啡肽（ME）、亮氨酸脑啡肽（LE）、苯丙-甲硫-精-苯丙酰胺（FMRF酰胺）、D-丙氨酸2、N-甲基苯丙氨酸4、甲硫氨酸（O）5-亮氨酸脑啡肽（FK 33-834）、甲硫氨酸脑啡肽精氨酸6精氨酸7（ME arg6 arg7）和β-内啡肽在浓度高达10^(-5)M时，对离体心房的基础搏动率均无影响。然而，脑啡肽可显著减弱去甲肾上腺素（NE）对心房率的正性变时作用。因此，在10^(-7)M ME存在时，NE的最大正性变时作用（在250克大鼠中，10^(-5)M NE剂量下，心率从317±7.0次/分钟增加到473±7.3次/分钟）降低了42%。加入10^(-7)M纳洛酮可完全阻断ME的作用，纳洛酮本身对NE诱导的正性变时作用或基础搏动率无影响。ME减弱NE诱导的正性变时作用的剂量-效应曲线呈钟形，即10^(-8)M和10^(-5)M ME对NE的正性变时作用均无显著影响。其他脑啡肽的作用方式与ME相似；LE（10^(-7)M）和FK 33-834（10^(-8)M）分别使NE诱导的最大正性变时作用降低42%和27%。软体动物心脏兴奋肽FMRF酰胺（10^(-7)M）也使NE的最大正性变时作用降低约30%。相比之下，β-内啡肽对NE刺激心房率无显著影响。我们得出结论，脑啡肽可在体外调节大鼠心房的去甲肾上腺素能反应性。讨论了这种相互作用可能的生理相关性。
