Forstner J, Maxwell B, Roomi N
Am J Physiol. 1981 Nov;241(5):G443-50. doi: 10.1152/ajpgi.1981.241.5.G443.
Intestinal glycoprotein synthesis and secretion were measured in vivo and in vitro in rats treated for 7 days with reserpine. Goblet cell mucin was measured by radioimmunoassay. Reserpine-treated rats contained 1.4 times more mucin in intestinal tissue than control rats (P less than 0.05) and incorporated [1-14C]glucosamine in vivo at 1.52 times the rate of controls (P less than 0.01). Intestinal slices incubated for 90 min in vivo incorporated 1.4 times more [14C]glucosamine (P less than 0.001) and 3.0 times more [3H]threonine (P less than 0.01) into protein of reserpine-treated tissue than controls. The extra 14C was localized to mucin and to smaller components that had affinity for Concanavalin-A-Sepharose, did not bind to mucin antibody, and were therefore nonmucin glycopeptides. In vitro secretion of mucin was three times greater for reserpine-treated tissue than for control tissue (P less than 0.0001). There was an impairment in the mucin secretory response of reserpine-treated tissue to the addition of cholera toxin. Thus, chronic reserpine treatment results primarily in a generalized increase in the rate of intestinal glycoprotein synthesis, subsequent accumulation in tissues, and an increased (but not fully proportional) secretion of mucin. We speculate that in cystic fibrosis a similar sequence of glycoprotein abnormalities may be responsible for the gradual obliteration of exocrine gland ducts with viscous mucus.
在给大鼠用利血平治疗7天的体内和体外实验中,测定了肠道糖蛋白的合成与分泌。通过放射免疫测定法测量杯状细胞粘蛋白。用利血平治疗的大鼠肠道组织中的粘蛋白含量比对照大鼠多1.4倍(P小于0.05),并且在体内掺入[1-14C]葡糖胺的速率是对照大鼠的1.52倍(P小于0.01)。在体内孵育90分钟的肠道切片中,用利血平治疗的组织比对照组织掺入粘蛋白的[14C]葡糖胺多1.4倍(P小于0.001),掺入蛋白质的[3H]苏氨酸多3.0倍(P小于0.01)。额外的14C定位于粘蛋白和对伴刀豆球蛋白A-琼脂糖有亲和力的较小成分,不与粘蛋白抗体结合,因此是非粘蛋白糖肽。用利血平治疗的组织中粘蛋白的体外分泌量是对照组织的三倍(P小于0.0001)。用利血平治疗的组织对霍乱毒素添加的粘蛋白分泌反应存在损害。因此,长期利血平治疗主要导致肠道糖蛋白合成速率普遍增加,随后在组织中积累,以及粘蛋白分泌增加(但并非完全成比例)。我们推测,在囊性纤维化中,类似的糖蛋白异常序列可能是外分泌腺导管被粘性粘液逐渐阻塞的原因。