title: Changes in submaxillary gland gene expression in F344 rats by multiple dosing of theophylline.
abstract: Multiple exposure to theophylline, a phosphodiesterase (PDE) inhibitor, induces acinar hypertrophy in the salivary gland. This study examined the effect of theophylline on the gene expression of secretory proteins and phosphodiesterases in the submaxillary gland. Male F344 rats received saline or theophylline (50 mg/kg) intraperitoneally for 4 days. The gene expressions for the secretory protein, cystatin S (CysS), and PDE subfamilies 3A and 4D in the submaxillary gland were quantified using RT-PCR. Theophylline exposure resulted in a sustained increase in mRNA expression for CysS and PDE3A, but PDE4D gene expression was unchanged. Our results suggest that submaxillary hypertrophy is primarily caused by the enhanced transcription of CysS, and that the transcription of each PDE subfamily gene is regulated differently.
authors.affiliation: Drug Safety Research Laboratories, Astellas Pharma Inc., Azusawa, Itabashi, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kajikawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kigami
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Kunio
authors.initials: K
authors.lastname: Doi
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000032:analysis; D000818:Animals; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D015891:Cystatins / Q000032:analysis; D015870:Gene Expression; D007274:Injections, Intraperitoneal; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010727:Phosphoric Diester Hydrolases; D051381:Rats; D011916:Rats, Inbred F344 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055333:Salivary Cystatins; D013363:Submandibular Gland / Q000737:chemistry* / Q000166:cytology; D013806:Theophylline / Q000008:administration & dosage*
chemical_list: C525174:Cyss protein, rat; D015891:Cystatins; D010726:Phosphodiesterase Inhibitors; D055333:Salivary Cystatins; D013806:Theophylline; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517290:Pde3a protein, rat