Sialagogue-stimulated protein phosphorylation related to ornithine decarboxylase induction in cultured rat parotid explants

Effects of Sialagogues on Ornithine Decarboxylase Induction and Proto-oncogene Expression in Murine Parotid Gland

“…Effects of monensin and polymyxin B on IPR-and CC-induced increases in mRNA levels.-We next investigated the relationship between elevations ofproto-oncogene mRNA levels and ODC induction using monensin and polymyxin B, which are specific inhibitors ofIPR-and CC-dependent ODC induction, respectively (Ueno et al, 1991b). We have reported that neither monensin nor polymyxin B inhibits sialagogue-dependent amylase secretion or the incorporation of phosphate into nucleic acids and total cellular proteins in cultured parotid explants.…”

“…4, the degrees of sialagogue-enhanced expressions of four proto-oncogenes were roughly proportional to the subsequent increases in ODC induction and DNA synthesis (Kikuchi et al, 1987), the effectiveness ofthe sialagogues being in the order IPR > CC > MTX. Studies on the relationship between proto-oncogene expression and ODC induction with use of the sialagogue-specific inhibitors of ODC induction, monensin and polymyxin B (Ueno et al, 1991b), showed that depression of ODC gene expression was preceded by decreases in c-fos and c-jun transcripts (Table 2). IPRstimulated ODC gene expression was completely abolished by cycloheximide, which must inhibit the syntheses of Fos and Jun proteins.…”

“…These stimulations were roughly proportional to the sialagogue-induced increases in amylase secretion, the order ofeffectiveness ofthe sialagogues being IPR > CC > MTX. Regardless of the type of sialagogue, the maximal increases of protein phosphorylation, ODC activity, and DNA synthesis were detected two, six, and 24 h, respectively, after stimulation ofthe parotid by the sialagogues (Ueno et al, 1991b). Experiments on the time-dependence of the effects of IPR and CC showed that parotid explants must be cultured with these agonists for at least four and 12 h for maximal increases in ODC activity and DNA synthesis, respectively (Inoue et al, 1985;Kikuchi et al, 1987).…”