A protein kinase inhibitor H-7 induces process extrusion in fetal rat thyroid 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 kinase inhibitors on the induction of neuronal phenotypes in the rat thyroid C-cells in vitro. In a primary culture of 16-day-old fetal rat thyroid glands, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7, 25-75 microM) 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, selective inhibitors for cyclic nucleotide-dependent protein kinases such as N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004, 25-200 microM) and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89, 0.25-20 microM) failed to induce process extrusion or the expression of highly polysialylated NCAM in fetal rat C-cells. In cultured C-cells of adult origin, H-7 failed to induce marked process elongation or the expression of highly polysialylated NCAM. These results suggest that 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.
Nishiyama
I
I
Komazawa Women's Junior College, Tokyo, Japan.
Ogiso
M
M
Seki
T
T
Oota
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology*; D000818:Animals; D002116:Calcitonin / Q000096:biosynthesis*; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D066298:In Vitro Techniques; D008297:Male; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis*; D009432:Neural Crest / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010641:Phenotype; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland
D019006:Neural Cell Adhesion Molecules; D019319:Okadaic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002116:Calcitonin; D011494:Protein Kinases