A PROTEIN-KINASE INHIBITOR H-7 INDUCES PROCESS EXTRUSION IN FETAL-RATTHYROID C-CELLS IN-VITRO

Calcitonin-producing cells (C-cells) are endocrine cells derived from the neural crest. We examined the effects of three types of protein ki nase inhibitors on the induction of neuronal phenotypes in the rat thy roid C-cells in vitro. In a primary culture of 16-day-old fetal rat th yroid glands, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochl oride (H-7, 25-75 mu M) induced both process extrusion and expression of highly polysialylated neural cell adhesion molecule (NCAM) in the C -cells. These effects of H-7 were completely prevented by okadaic acid , a potent protein phosphatase inhibitor. In contrast to H-7, selectiv e inhibitors for cyclic nucleotide-dependent protein kinases such as N -(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004, 2 5-200 mu M) and romocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H- 89, 0.25-20 mu M) failed to induce process extrusion or the expression of highly polysialylated NCAM in fetal rat C-cells. In cultured C-cel ls of adult origin, H-7 failed to induce marked process elongation or the expression of highly polysialylated NCAM. These results suggest th at the morphological plasticity of the fetal C-cells depends upon the degree of phosphorylation of some proteins, and that the plasticity of adult C-cells are more restricted than that of fetal origin.