ABSTRACT
This chapter demonstrates that the inhibition in intestinal growth probably is due to a suppression of cell proliferation in the crypt cell compartment. It focuses on calmodulin and suggests that the antiproliferative and chemoprotective effect of calcium may occur via interaction with this calcium regulatory protein. The chapter demonstrates the inhibition of colonic mucosal ornithine decarboxylase (ODC) and tyrosine kinase activity by the calmodulin antagonist trifluoperazine. It shows that the hyperproliferative activity induced by azoxymethane can be suppressed to a similar degree with trifluoperazine as with calcium. Ornithine is the substrate for the biosynthesis of the polyamines putrescine, spermidine, and spermine in mammalian cells. It is decarboxylated by ornithine decarboxylase to form putrescine as the first and often rate-limiting step in polyamine biosynthesis. ODC has one of the shortest half-lives known for a mammalian enzyme, ranging from 7 to 15 minutes in different reports, and is highly and rapidly inducible by many growth stimuli.
