Majumdar A P, Wahby M
Department of Veterans Affairs Medical Center, Allen Park, Michigan 48101.
Proc Soc Exp Biol Med. 1993 Mar;202(3):365-70. doi: 10.3181/00379727-202-43548.
The present investigation examines the changes in tyrosine kinase (Tyr-k) activity and tyrosine-specific phosphorylation of membrane protein(s) in isolated gastric mucosal cells from young (3 months) and aged (22 months) Fischer-344 rats after exposure to gastrin. In mucosal cells from young rats, a 15-min time course study revealed a steady rise of Tyr-k activity for the first 2 min in response to 10(-9) M gastrin (G-17 I), whereafter the enzyme activity decreased sharply. In these cells, a significant 90% (P < 0.001) increase in the enzyme activity was observed only after 30 sec of exposure to gastrin, with maximal stimulation (124%; P < 0.001) occurring after 2 min. These increases were also associated with a 2- to 3-fold rise in tyrosine-specific phosphorylation of 55-, 80-, and 100-kDa membrane proteins. In contrast, in mucosal cells from aged rats, neither Tyr-k activity nor tyrosine phosphorylation of membrane proteins was affected by gastrin with doses up to 10(-6) M. Our observation of an immediate induction of Tyr-k activity and tyrosine phosphorylation of certain membrane proteins by gastrin in gastric mucosal cells from young, but not from aged, rats suggests that these events may play an important role regulating some of the physiologic actions of gastrin at different stages of life.
本研究检测了年轻（3个月）和老年（22个月）Fischer-344大鼠分离的胃黏膜细胞在暴露于胃泌素后酪氨酸激酶（Tyr-k）活性和膜蛋白酪氨酸特异性磷酸化的变化。在年轻大鼠的黏膜细胞中，一项15分钟的时程研究显示，在10⁻⁹M胃泌素（G-17 I）作用下，最初2分钟Tyr-k活性稳步上升，此后酶活性急剧下降。在这些细胞中，仅在暴露于胃泌素30秒后，酶活性就显著增加了90%（P<0.001），在2分钟时达到最大刺激（124%；P<0.001）。这些增加还伴随着55 kDa、80 kDa和100 kDa膜蛋白酪氨酸特异性磷酸化增加2至3倍。相比之下，在老年大鼠的黏膜细胞中，高达10⁻⁶M的胃泌素剂量对Tyr-k活性和膜蛋白酪氨酸磷酸化均无影响。我们观察到胃泌素能立即诱导年轻而非老年大鼠胃黏膜细胞中Tyr-k活性和某些膜蛋白的酪氨酸磷酸化，这表明这些事件可能在调节胃泌素在生命不同阶段的某些生理作用中发挥重要作用。
