Meyer-Alber A, Fetz I, Waschulewski I H, Höcker M, Fölsch U R, Schmidt W E
I. Department of Medicine, Christian-Albrechts-University, Kiel, Germany.
Biochem Biophys Res Commun. 1994 Jun 30;201(3):1470-6. doi: 10.1006/bbrc.1994.1869.
The effects of the serine/threonine phosphatase inhibitors calyculin A, okadaic acid and the calmodulin antagonist W-7 on amylase secretion were studied in pancreatic acini. Calyculin A and okadaic acid dose-dependently inhibited amylase secretion to basal levels when stimulated with the intracellularly acting secretagogues thapsigargin, 8-br-cAMP or PMA. W-7 dose-dependently inhibited thapsigargin- or 8-br-cAMP-induced amylase secretion. In combination, thapsigargin, 8-br-cAMP and PMA induced amylase secretion comparable to the stimulation by cholecystokinin. Their effect was significantly inhibited by calyculin A, okadaic acid or W-7. These data imply that type 1- and 2b-phosphatases and calmodulin play a key role in the stimulation of exocrine pancreatic secretion at a distal step of both the Ca2+/IP3- and cAMP-mediated signal-transduction pathways.
在胰腺腺泡中研究了丝氨酸/苏氨酸磷酸酶抑制剂花萼海绵诱癌素A、冈田酸以及钙调蛋白拮抗剂W-7对淀粉酶分泌的影响。当用细胞内作用的促分泌剂毒胡萝卜素、8-溴-cAMP或佛波酯刺激时,花萼海绵诱癌素A和冈田酸剂量依赖性地将淀粉酶分泌抑制至基础水平。W-7剂量依赖性地抑制毒胡萝卜素或8-溴-cAMP诱导的淀粉酶分泌。毒胡萝卜素、8-溴-cAMP和佛波酯共同作用诱导的淀粉酶分泌与胆囊收缩素刺激相当。它们的作用被花萼海绵诱癌素A、冈田酸或W-7显著抑制。这些数据表明,1型和2b型磷酸酶以及钙调蛋白在Ca2+/肌醇三磷酸和cAMP介导的信号转导途径的远端步骤中,对外分泌性胰腺分泌的刺激起关键作用。