Theophylline down-regulates adenosine receptor function.
Chronic treatment of animals with caffeine or theophylline has been reported to increase the number of adenosine receptors in the CNS detected by ligand binding, but few functional studies have been performed. In the present study adenosine enhanced depolarising responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in slices of mouse cerebral cortex. This effect was blocked acutely by theophylline but not by theophylline given 24 h previously. Twenty-four hours after 2 weeks of treatment with this antagonist, however (10 or 100 mg/kg/day) adenosine was no longer effective, sensitivity recovering subsequently. Theophylline treatment also reduced sensitivity to (-)-isoprenaline but not 5-hydroxytryptamine. It is concluded that changes of adenosine receptor number in the brain do not necessarily reflect the induced changes of receptor function.
Dept. of Pharmacology, University of Glasgow, U.K.
J
J
Mally
J H
JH
Connick
T W
TW
Stone
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D016202:N-Methylaspartate; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology*
D011983:Receptors, Purinergic; D001224:Aspartic Acid; D012701:Serotonin; D016202:N-Methylaspartate; D013806:Theophylline; D000241:Adenosine; D007545:Isoproterenol