Schäfer C, Steffen H, Printz H, Göke B
Department of Internal Medicine, Philipps-University of Marburg, Germany.
Can J Physiol Pharmacol. 1994 Oct;72(10):1138-47. doi: 10.1139/y94-161.
Diastereomers of adenosine 3',5'-phosphorothioate activate cAMP-dependent protein kinases (cAMP-PK) in vitro. We found that these compounds are highly selective tools to monitor cAMP-dependent PKA activation and its effect on amylase exocytosis from pancreatic acini. In permeabilized rat acinar cells, (Sp)-cAMPS dose-dependently stimulated amylase secretion, while (Rp)-cAMPS inhibited (Sp)-cAMPS-induced amylase release. In intact rat acini, 8-Br-(Rp)-cAMPS reduced the secretory responses to secretin, vasoactive intestinal polypeptide (VIP), 8-Br-cAMP, and 8-Br-(Sp)-cAMPS, but not to cerulein. Another derivative, dibutyryl-(Rp)-cAMPS, induced a small inhibitory effect against 8-Br-(Sp)-cAMPS and VIP, which was overlapped by an unspecific stimulatory effect on amylase exocytosis induced by the degradation product butyrate. Furthermore, (Sp)-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'- monophosphorothioate ((Sp)-5,6-DCl-cBIMPS), a specific cAMP-PK activator, induced a maximal induction of cAMP-PK activity, but its stimulation of amylase secretion was less than that by secretin. (Sp)-5,6-DCl-cBIMPS regulated the phosphorylation of several proteins, which were also affected by secretin. However, secretin had additional effects. Its action was most likely mediated by a dual effect on the cAMP and the calcium pathway. Our results indicate that the cAMP-dependent pathway is involved in amylase exocytosis from rat pancreatic acini.
腺苷3',5'-硫代磷酸酯的非对映异构体在体外可激活环磷酸腺苷依赖性蛋白激酶（cAMP-PK）。我们发现这些化合物是监测cAMP依赖性蛋白激酶A激活及其对胰腺腺泡淀粉酶胞吐作用影响的高度选择性工具。在通透的大鼠腺泡细胞中，（Sp）-cAMPS以剂量依赖方式刺激淀粉酶分泌，而（Rp）-cAMPS则抑制（Sp）-cAMPS诱导的淀粉酶释放。在完整的大鼠腺泡中，8-溴-（Rp）-cAMPS降低了对促胰液素、血管活性肠肽（VIP）、8-溴-cAMP和8-溴-（Sp）-cAMPS的分泌反应，但对蛙皮素的反应无影响。另一种衍生物二丁酰-（Rp）-cAMPS对8-溴-（Sp）-cAMPS和VIP有轻微抑制作用，但其降解产物丁酸盐对淀粉酶胞吐有非特异性刺激作用，二者作用相互重叠。此外，（Sp）-5,6-二氯-1-β-D-呋喃核糖基苯并咪唑-3',5'-单硫代磷酸酯（（Sp）-5,6-DCl-cBIMPS）是一种特异性cAMP-PK激活剂，可最大程度诱导cAMP-PK活性，但其对淀粉酶分泌的刺激作用小于促胰液素。（Sp）-5,6-DCl-cBIMPS调节了几种蛋白质的磷酸化，这些蛋白质也受促胰液素影响。然而，促胰液素还有其他作用。其作用很可能是通过对cAMP和钙途径的双重作用介导的。我们的结果表明，cAMP依赖性途径参与大鼠胰腺腺泡淀粉酶的胞吐作用。
