Małecka-Panas E, Tureaud J, Majumdar A P
Department of Digestive Tract Diseases and Metabolic Disorders, Medical School, Lódź, Poland.
Acta Biochim Pol. 1996;43(3):539-46.
Postreceptor regulation of the trophic action of gastrin is not fully elucidated. Tyrosine kinase (Tyr-kinase) has been associated with receptors of a number of growth factors and plays an important role in regulation of cellular growth within the gastrointestinal tract. The aim of this study was to determine, whether Tyr-kinase plays a role in mediating the growth promoting action of gastrin and whether phospholipase C (PLC) is involved in the signal transduction pathway. Colonocytes isolated from Fischer 344 rats were incubated for 2 min with gastrin (10(-8) M) and assayed for Tyr-kinase and PLC activities. Incubations with gastrin resulted in 60%-70% rise in Tyr-kinase and 150%-200% rise in PLC activities over the corresponding basal levels. When processed separately, in proximal colon Tyr-kinase activation by gastrin was 15%-20%, while in distal colon 70%-80% as compared to the buffer control. Gastrin activation of both Tyr-kinase and PLC was abolished by Tyr-kinase inhibitor, tyrphostin-25 (3.2 microM) and was not affected by staurosporine (20 ng/ml). We conclude that Tyr-kinase is involved in the mechanism of trophic action of gastrin, and PLC activation appears to be the next step in the signal transduction pathway.
胃泌素营养作用的受体后调节尚未完全阐明。酪氨酸激酶（Tyr激酶）与多种生长因子的受体相关，在胃肠道细胞生长调节中起重要作用。本研究的目的是确定Tyr激酶是否在介导胃泌素的促生长作用中发挥作用，以及磷脂酶C（PLC）是否参与信号转导途径。从Fischer 344大鼠分离的结肠细胞与胃泌素（10^(-8) M）孵育2分钟，然后检测Tyr激酶和PLC活性。与胃泌素孵育导致Tyr激酶活性比相应基础水平升高60%-70%，PLC活性升高150%-200%。单独处理时，与缓冲液对照相比，胃泌素在近端结肠激活Tyr激酶的比例为15%-20%，而在远端结肠为70%-80%。Tyr激酶抑制剂曲磷胺（3.2 microM）可消除胃泌素对Tyr激酶和PLC的激活作用，而星形孢菌素（20 ng/ml）对此无影响。我们得出结论，Tyr激酶参与胃泌素营养作用机制，PLC激活似乎是信号转导途径的下一步。
