Gastrin-mediated changes in tyrosine kinases in isolated gastric mucosal cells from young and aged rats.

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.