Jhamandas K, Sutak M
Br J Pharmacol. 1980;71(1):201-10. doi: 10.1111/j.1476-5381.1980.tb10927.x.
1 Methionine (Met)-enkephalin, leucine (Leu)-enkephalin and their synthetic analogues were tested for effects on the spontaneous release of cortical acetylcholine (ACh) in vivo. The ability of naloxone to reverse the action of enkephalins on ACh release was compared with its action against morphine. An enkephalin analogue, structurally related to Met-enkephalin, was tested for opiate antagonistic activity in ACh release experiments. 2 Intraventricular administration of Met-enkephalin, Leu-enkephalin, D-Ala2-Met5-enkephalinamide (DALA) and D-Ala2-D-Leu5-enkephalin (DALEU) produced a dose-related inhibition of cortical ACh release. Met- and Leu-enkephalin were very similar both in their potency and the time course of their action on ACh release. Both DALA and DALEU were more potent and had a longer duration of action than Leu-enkephalin. Systemic injections of two pentapeptides, D-Met2-Pro5-enkephalinamide and D-Ala2-MePhe4-Met5(O)-ol-enkephalin (33,824), produced a sustained inhibition of cortical ACh release. 3 Naloxone, administered systemically following the depression of ACh release induced by either intraventricular injections of enkephalins (DALA or DALEU), or systemic injections of enkephalins (D-Met2-Pro5-enkephalinamide or 33,824), reversed this depression and restored the release to baseline levels. The effect of D-Met2-Pro5-enkephalinamide on the release of ACh was reversed by naloxone with difficulty. Naloxone also reversed the inhibitory effect of systemic morphine and this reversal was associated with a large overshoot of ACh release. The latter was never observed in the enkephalin experiments. 4 Intraventricular injection of the pentapeptide, D-Ala2-D-Ala3-Met5-enkephalinamide (TAAPM), at doses that did not influence the basal ACh release, blocked or reversed the inhibitory effect of morphine on this release. This peptide did not block the effect of the non-opiate, chlorpromazine, under similar conditions. In two experiments TAAPM failed to reverse the inhibition of ACh release produced by systemically injected enkephalin, D-Met2-Pro5-enkephalinamide. 5 Effects of morphine and enkephalin on ACh release are discussed in terms of their action on difference opiate receptors.
对甲硫氨酸（Met）-脑啡肽、亮氨酸（Leu）-脑啡肽及其合成类似物进行了体内对皮质乙酰胆碱（ACh）自发释放影响的测试。将纳洛酮逆转脑啡肽对ACh释放作用的能力与其对抗吗啡的作用进行了比较。在ACh释放实验中，对一种与Met-脑啡肽结构相关的脑啡肽类似物进行了阿片拮抗活性测试。
脑室内注射Met-脑啡肽、Leu-脑啡肽、D-Ala2-Met5-脑啡肽酰胺（DALA）和D-Ala2-D-Leu5-脑啡肽（DALEU）产生了与剂量相关的皮质ACh释放抑制。Met-和Leu-脑啡肽在效力及其对ACh释放作用的时间进程方面非常相似。DALA和DALEU都比Leu-脑啡肽更有效且作用持续时间更长。两种五肽D-Met2-Pro5-脑啡肽酰胺和D-Ala2-MePhe4-Met5(O)-醇-脑啡肽（33,824）的全身注射产生了皮质ACh释放的持续抑制。
在脑室内注射脑啡肽（DALA或DALEU）或全身注射脑啡肽（D-Met2-Pro5-脑啡肽酰胺或33,824）诱导ACh释放降低后全身给予纳洛酮，可逆转这种降低并使释放恢复到基线水平。纳洛酮很难逆转D-Met2-Pro5-脑啡肽酰胺对ACh释放的作用。纳洛酮还逆转了全身吗啡的抑制作用，且这种逆转与ACh释放的大幅超调有关。在脑啡肽实验中从未观察到后者。
脑室内注射五肽D-Ala2-D-Ala3-Met5-脑啡肽酰胺（TAAPM），在不影响基础ACh释放的剂量下，阻断或逆转了吗啡对该释放的抑制作用。在类似条件下，该肽不阻断非阿片类药物氯丙嗪的作用。在两个实验中，TAAPM未能逆转全身注射脑啡肽D-Met2-Pro5-脑啡肽酰胺所产生的ACh释放抑制。
根据吗啡和脑啡肽对不同阿片受体的作用讨论了它们对ACh释放的影响。
