Plusczyk T, Piiper A, Schulz I
Max-Planck-Institut für Biophysik, Frankfurt am Main, Germany.
FEBS Lett. 1991 Dec 16;295(1-3):89-92. doi: 10.1016/0014-5793(91)81392-l.
In this study we have examined the effects of prostaglandin E2 (PGE2), the cyclooxygenase inhibitor, indomethacin, and a protein kinase A inhibitor (PKA-I) on the Cl- conductance in isolated zymogen granules (ZG) from cholecystokinin octapeptide (CCK-8) pre-stimulated pancreatic acini. The Cl- conductance in isolated ZG from CCK-8 pre-stimulated rat pancreatic acini increases with increasing CCK-8 concentrations and decreases at supramaximal CCK-8 concentrations. The basal and CCK-8-stimulated Cl- conductance in ZG is inhibited by pretreatment of acini with PGE2 (10(-6) M). This PGE2-induced inhibition is abolished in the presence of PKA-I (20 U/ml). Furthermore, pretreatment of acini with indomethacin (10(-5) M) or PKA-I (20 U/ml) abolishes the decrease in the CL- conductance at supramaximal CCK-8 concentrations (10(-9) M). We conclude that the inhibition of the CL- conductance in isolated ZG at high CCK-8 concentrations is mediated by an enhanced production of PGE2, and that PGE2 operates by stimulating adenylate cyclase (AC) with a consequent rise in cAMP and activation of PKA.
在本研究中，我们检测了前列腺素E2（PGE2）、环氧化酶抑制剂吲哚美辛和蛋白激酶A抑制剂（PKA-I）对从经胆囊收缩素八肽（CCK-8）预刺激的胰腺腺泡中分离出的酶原颗粒（ZG）氯离子电导的影响。从CCK-8预刺激的大鼠胰腺腺泡中分离出的ZG中的氯离子电导随CCK-8浓度增加而升高，在CCK-8浓度超过最大浓度时降低。用PGE2（10^(-6) M）预处理腺泡可抑制ZG中的基础氯离子电导和CCK-8刺激的氯离子电导。在存在PKA-I（20 U/ml）的情况下，这种PGE2诱导的抑制作用被消除。此外，用吲哚美辛（10^(-5) M）或PKA-I（20 U/ml）预处理腺泡可消除在CCK-8超最大浓度（10^(-9) M）时氯离子电导的降低。我们得出结论，在高CCK-8浓度下，分离的ZG中氯离子电导的抑制是由PGE2生成增加介导的，并且PGE2通过刺激腺苷酸环化酶（AC）起作用，从而导致cAMP升高和PKA激活。
