Long-term theophylline treatment changes the effects of angiotensin II and adenosinergic agents on the seizure threshold.

The effects of angiotensin II (ANG II), sarmesin, losartan, PD 123319, and adenosine A (1) receptor agonist N(6)-cyclopentyladenosine (CPA) administered i.c.v. in untreated and in theophylline-treated male mice (50 mg/kg i.p. twice daily for 14 days) were studied on the pentylenetetrazol (PTZ) seizure threshold. The threshold was increased after long-term theophylline treatment. ANG II, sarmesin, and CPA increased the threshold in theophylline-untreated mice, whereas it decreased the threshold in theophylline-treated animals. Losartan did not change the threshold in theophylline-untreated mice but decreased it in theophylline-treated animals. PD 123319 did not change the seizure threshold both in theophylline-untreated and -treated mice. Taken together, the data demonstrated that repeated exposure to theophylline selectively changes the effects of ANG II and adenosinergic agents on the PTZ seizure threshold. The results indicate that both angiotensin AT(1) and adenosine A(1) receptor subtypes could possess interactive mechanisms of adaptation to chronic theophylline treatment.