Fóris G, Medgyesi G A, Hauck M
Mol Cell Biochem. 1986 Feb;69(2):127-37. doi: 10.1007/BF00224759.
Met-enkephalin (ME) exerts a bimodal effect on functional activities of rat peritoneal macrophages (PM); in a range of low concentration (10(-9)-10(-7)M) antibody dependent cellular cytotoxicity (ADCC) was markedly stimulated with a simultaneous decrease of Fc gamma receptor (Fc gamma R) medicated phagocytosis while the opposite was observed at 10(-6)-10(-5)M concentrations. Studying the possible underlying mechanism(s) the followings were recorded: (1) ME in all applied concentrations induced an early Na+ influx which was followed by a Ca2+ efflux in the range of low concentrations. In the range of high concentrations Na+ influx was accompanied by a Ca2+ influx. (2) ME at 10(-8) M concentration induced a rise in cGMP level with a plateau in the 60-120th min of incubation. This effect was prevented by 10(-5) M of naloxone. At 10(-6) M concentration a transient rise of cAMP level was recorded which was not affected by naloxone. (3) Verapamil in 10(-6) M abolished both the Ca2+ influx and the rise in cAMP level induced by 10(-6)-10(-5) M ME but not the rise in cGMP level induced by lower ME concentrations. (4) cAMP elevation by high ME concentrations was abolished by enkephalinase inhibitory puromycin. (5) PM-enkephalinase as assessed by the cleavage of fluorogenic substrate L-alanine beta naphthylamide (ABNA), was inhibited by 10(-6)-10(-5) M of ME. This inhibition was abolished by verapamil, but not affected by naloxone. In the range of low concentrations ME appears to act on specific delta opioid receptors and its action is positively coupled to guanylate cyclase. In relatively higher concentrations ME-action is not mediated by specific delta opioid receptors and it appears to involve Ca2+ influx, adenylate cyclase activation as well as the processing of hormone by PM-enkephalinase.
甲硫氨酸脑啡肽（ME）对大鼠腹腔巨噬细胞（PM）的功能活动具有双相作用；在低浓度范围（10⁻⁹ - 10⁻⁷M），抗体依赖性细胞毒性（ADCC）显著增强，同时Fcγ受体（FcγR）介导的吞噬作用降低，而在10⁻⁶ - 10⁻⁵M浓度时观察到相反的情况。在研究可能的潜在机制时，记录到以下情况：（1）所有应用浓度的ME均诱导早期Na⁺内流，随后在低浓度范围内出现Ca²⁺外流。在高浓度范围内，Na⁺内流伴随着Ca²⁺内流。（2）10⁻⁸M浓度的ME诱导cGMP水平升高，在孵育60 - 120分钟时达到平台期。该效应被10⁻⁵M纳洛酮阻断。在10⁻⁶M浓度时，记录到cAMP水平短暂升高，且不受纳洛酮影响。（3）10⁻⁶M维拉帕米消除了10⁻⁶ - 10⁻⁵M ME诱导的Ca²⁺内流和cAMP水平升高，但未消除较低ME浓度诱导的cGMP水平升高。（4）高浓度ME引起的cAMP升高被脑啡肽酶抑制剂嘌呤霉素消除。（5）通过荧光底物L - 丙氨酸β - 萘酰胺（ABNA）的裂解评估的PM - 脑啡肽酶被10⁻⁶ - 10⁻⁵M的ME抑制。这种抑制被维拉帕米消除，但不受纳洛酮影响。在低浓度范围内，ME似乎作用于特定的δ阿片受体，其作用与鸟苷酸环化酶正偶联。在相对较高浓度下，ME的作用不是由特定的δ阿片受体介导的，似乎涉及Ca²⁺内流、腺苷酸环化酶激活以及PM - 脑啡肽酶对激素的加工。
