Saunders W S, Thornhill J A
Br J Pharmacol. 1985 Jun;85(2):513-22. doi: 10.1111/j.1476-5381.1985.tb08888.x.
Inotropic actions of the endogenous enkephalins, leucine enkephalin [( Leu] enkephalin) and methionine enkephalin [( Met] enkephalin), and derivatives, [D-Ala2-methionine] enkephalinamide (DAMEA) and [D Ala2-leucine]enkephalinamide (DALEA) were tested, alone or in combination with noradrenaline (NA), (+/-)-isoprenaline or carbachol, on electrically-stimulated atria excised from Sprague-Dawley, fatty, Zucker (fa/fa) and lean, hooded heterozygous (Fa/fa) rats. [Met] enkephalin, [Leu] enkephalin, DAMEA and DALEA (4 X 10(-7)M to 4 X 10(-4)M) caused no significant changes in atrial tension in any group compared to pre-injection control values or those following the infusion of Krebs-Henseleit control solution. NA and isoprenaline (10(-7) to 10(-6)M) caused significant, dose-related increases in atrial tension in each of the three strains of rats tested with the Fa/fa group showing the greatest change and fastest rate of tension development. [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 X 10(-6)M) infused concurrently with NA or isoprenaline (10(-6)M) evoked atrial tension changes within each group that were not different from those observed when NA or isoprenaline was administered alone. Carbachol (10(-9) and 10(-8)M) caused a dose-related decrease (10% and 30-40%, respectively, from pre-injection control values) in atrial tension in auricles excised from all three groups. Again, infusion of [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 X 10(-6)M) together with carbachol (10(-8)M) did not affect atrial tension changes of auricles isolated from any group compared to when carbachol was given alone. The results indicate that the endogenous pentapeptides, [( Met] or [Leu] enkephalin), or derivatives (DAMEA and DALEA) do not affect atrial tension of electrically-stimulated auricles isolated from Sprague-Dawley, fa/fa or Fa/fa rats. In addition, these pentapeptides do not modify the positive inotropic actions of NA or isoprenaline or the negative inotropic effects of carbachol. It is suggested that in vivo, the enkephalins or enkephalin derivatives do not have a direct action on the heart to alter myocardial contractility.
对内源性脑啡肽、亮氨酸脑啡肽[（Leu）脑啡肽]和甲硫氨酸脑啡肽[（Met）脑啡肽]及其衍生物[D - Ala2 - 甲硫氨酸]脑啡肽酰胺（DAMEA）和[D - Ala2 - 亮氨酸]脑啡肽酰胺（DALEA）的变力作用进行了测试，这些物质单独或与去甲肾上腺素（NA）、（±）-异丙肾上腺素或卡巴胆碱联合使用，作用于从斯普拉格 - 道利大鼠、肥胖型 Zucker（fa/fa）大鼠和瘦型有帽杂合子（Fa/fa）大鼠分离出的经电刺激的心房。与注射前对照值或输注克雷布斯 - 亨塞尔特对照溶液后的数值相比，[Met]脑啡肽、[Leu]脑啡肽、DAMEA和DALEA（4×10⁻⁷M至4×10⁻⁴M）在任何组中均未引起心房张力的显著变化。NA和异丙肾上腺素（10⁻⁷至10⁻⁶M）在用这三种品系大鼠进行测试时均引起心房张力显著的、剂量相关的增加，其中Fa/fa组变化最大且张力发展速率最快。与单独给予NA或异丙肾上腺素时相比，[Met]脑啡肽、[Leu]脑啡肽、DAMEA或DALEA（4×10⁻⁶M）与NA或异丙肾上腺素（10⁻⁶M）同时输注时，每组引起的心房张力变化并无差异。卡巴胆碱（10⁻⁹和10⁻⁸M）使从所有三组分离出的心房肌的心房张力出现剂量相关的降低（分别比注射前对照值降低10%和30 - 40%）。同样，与单独给予卡巴胆碱时相比，[Met]脑啡肽、[Leu]脑啡肽、DAMEA或DALEA（4×10⁻⁶M）与卡巴胆碱（10⁻⁸M）一起输注时，并未影响从任何组分离出的心房肌的心房张力变化。结果表明，内源性五肽[（Met）或（Leu）脑啡肽]或其衍生物（DAMEA和DALEA）不影响从斯普拉格 - 道利大鼠、fa/fa或Fa/fa大鼠分离出的经电刺激的心房肌的张力。此外，这些五肽不会改变NA或异丙肾上腺素的正性变力作用或卡巴胆碱的负性变力作用。提示在体内，脑啡肽或脑啡肽衍生物对心脏没有直接作用来改变心肌收缩力。
