Stimulation by theophylline and sildenafil of rat submandibular secretion of protein, epidermal growth factor and flow rate

In the present study, the effects of cAMP- and cGMP-phosphodiesterase (PDE) inhibitors, theophylline, and sildenafil on secretion of protein, amylase and epidermal growth factor (EGF) and the flow rate from rat submandibular saliva were examined in an acute experiment. Theophylline at doses of 25, 50, 85 mg kg(-1) and sildenafil at doses of 1, 2, 5 mg kg(-1) were administered intraperitoneally 2 h before saliva collection. Pure submandibular saliva was collected intraorally by microployethylene tubes under anesthesia using dissecting microscope. Theophylline at doses of 25, 50, 85 mg kg(-1) increased salivary flow rate to 197% (P < 0.01), 186% (P < 0.01), and 209% of control, respectively. Sildenafil at doses of 1, 2, 5 mg kg(-1) also increased flow rate to 232% (P < 0.01), 182% (P < 0.01), and 197% of control, respectively. Theophylline at doses of 25, 50, 85 mg kg(-1) increased total protein concentration to 98% (P < 0.01), 84% (P < 0.01), and 210% of control, respectively. Sildenafil at doses of 2 and 5 mg kg(-1) increased total protein concentration to 75% (P < 0.01), and 240% of control, respectively. Theophylline at dose of 85 mg kg(-1) increased EGF concentration to 60% (P < 0.01) of control. Sildenafil at doses of 2 and 5 mg kg(-1) increased EGF concentration to 44% (P < 0.05) and 90% (P < 0.01) of control, respectively. No statistically significant change was observed in amylase activity by administration of theophylline or sildenafil. The present results indicate that increasing intracellular levels of cAMP and cGMP have stimulatory effects on salivary functions. Regarding beneficiary effects of increased salivary flow rate and secretion of EGF in maintaining oral health, theophylline and sildenafil may find good places in some oral diseases. (C) 2003 Elsevier Ltd. All rights reserved.