Van Loon G R, Pierzchala K, Houdi A A, Kvetnanský R, Zeman P
Department of Medicine, University of Kentucky, Lexington.
Endocrinology. 1990 Apr;126(4):2196-204. doi: 10.1210/endo-126-4-2196.
Plasma concentrations of both native (pentapeptide plus its sulfoxide) and peptidase-derivable (trypsin followed by carboxypeptidase-B) Met-enkephalin showed brisk increases in response to the stresses of immobilization, hemorrhage, and electric footshock in conscious, freely moving, adult male rats. Daily exposure to 150-min periods of immobilization resulted in a maintained increase in baseline plasma concentrations of native Met-enkephalin 21.5 h after the sixth day and a further increase after 39 days. The plasma native Met-enkephalin response to acute immobilization was attenuated on day 7 and completely absent on day 40. Unstressed rats showed a plasma native Met-enkephalin response to hemorrhage of 15% blood volume and a further increase in response to 25% hemorrhage. Immediately after initial acute immobilization or 6 days of daily immobilization when plasma native Met-enkephalin was elevated but the response to acute immobilization was attenuated, plasma native Met-enkephalin responses to hemorrhage were also attenuated. Rats that had been immobilized daily for 40 days and showed no plasma native Met-enkephalin response to acute immobilization also showed no responses to hemorrhage. After 39 days of immobilization when there was no plasma native Met-enkephalin response to acute immobilization, there was also no response to footshock. Thus, development of tolerance or adaptive loss of plasma native Met-enkephalin response to immobilization with repeated exposure to this stressor is associated with cross-tolerance or adaptive loss of the responses to the stresses of hemorrhage or electric footshock. Development of tolerance and cross-tolerance of plasma responses of peptidase-derivable Met-enkephalin paralleled that of native Met-enkephalin. Thus, adaptation of plasma Met-enkephalin responses to repeated exposure to a stressor included both increased resting secretion and decreased acute responses to homotypic or novel stressors.
在清醒、自由活动的成年雄性大鼠中，天然形式（五肽及其亚砜）和肽酶衍生形式（胰蛋白酶后接羧肽酶B）的甲硫氨酸脑啡肽的血浆浓度，在受到固定、出血和电击足底等应激时均迅速升高。每天暴露于150分钟的固定应激中，在第六天之后的21.5小时，天然甲硫氨酸脑啡肽的基线血浆浓度持续升高，39天后进一步升高。血浆天然甲硫氨酸脑啡肽对急性固定应激的反应在第7天减弱，在第40天完全消失。未受应激的大鼠，血浆天然甲硫氨酸脑啡肽对失血15%有反应，对失血25%反应进一步增强。在最初急性固定或每日固定6天后，当血浆天然甲硫氨酸脑啡肽升高但对急性固定的反应减弱时，血浆天然甲硫氨酸脑啡肽对出血的反应也减弱。每日固定40天且对急性固定无血浆天然甲硫氨酸脑啡肽反应的大鼠，对出血也无反应。固定39天后，当对急性固定无血浆天然甲硫氨酸脑啡肽反应时，对电击足底也无反应。因此，反复暴露于该应激源导致对固定应激的耐受性发展或血浆天然甲硫氨酸脑啡肽反应的适应性丧失，与对出血或电击足底应激反应的交叉耐受性或适应性丧失相关。肽酶衍生的甲硫氨酸脑啡肽血浆反应的耐受性和交叉耐受性发展与天然甲硫氨酸脑啡肽平行。因此，血浆甲硫氨酸脑啡肽反应对反复暴露于应激源的适应性包括静息分泌增加和对同型或新应激源的急性反应减少。
