Effects of sialagogues on ornithine decarboxylase induction and proto-oncogene expression in murine parotid gland.
The mechanism of a sialagogue-induced increase in ornithine decarboxylase (ODC) activity and the expressions of proto-oncogenes in murine parotid gland were investigated by use of isoproterenol (IPR), carbachol (CC), and methoxamine (MTX). The results were as follows: (1) The three sialagogues had similar effects on the parotid in vivo (mouse parotid after a single injection of IPR) and/or in vitro (rat parotid explants cultured on siliconized lens paper floating on 199 medium containing IPR, CC, or MTX), the order of their effectiveness being IPR > CC > MTX. (2) Northern/dot and Western blot analyses revealed that the sialagogues elevated the steady-state levels of ODC mRNA and ODC protein to maxima at two h and six h, respectively, after stimulation. The increases were roughly proportional to those in ODC activity, suggesting that sialagogue-dependent enzyme induction is regulated at the transcriptional level. (3) The mRNAs of four of nine proto-oncogenes examined showed sialagogue-dependent increases to maxima at 30 min (c-fos) or 60 min (c-jun, c-myc, and c-src) after the beginning of stimulation. These increases were all transient, with the levels returning to the control values (without sialagogue) within 60 min. (4) The IPR-dependent elevations of ODC activity and the mRNAs of ODC, c-fos, and c-jun were inhibited by monensin, but not by polymyxin B. On the other hand, the CC-dependent increases in these parameters were inhibited by polymyxin B but not by monensin.(ABSTRACT TRUNCATED AT 250 WORDS)
Kawano
M
M
Department of Biochemistry, School of Dentistry, University of Tokushima, Japan.
Ueno
A
A
Ashida
Y
Y
Matsumoto
N
N
Inoue
H
H
D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D016391:Genes, src / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D008985:Monensin / Q000494:pharmacology; D009924:Organ Culture Techniques; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D010306:Parotid Gland / Q000187:drug effects* / Q000201:enzymology*; D011112:Polymyxin B / Q000494:pharmacology; D011519:Proto-Oncogenes / Q000187:drug effects* / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000546:Amanitins; D012333:RNA, Messenger; D002217:Carbachol; D008985:Monensin; D003513:Cycloheximide; D009955:Ornithine Decarboxylase; D008729:Methoxamine; D011112:Polymyxin B; D007545:Isoproterenol