Changes in noradrenaline release and in beta receptor number in rat hippocampus following long-term treatment with theophylline or L-phenylisopropyladenosine.
The administration of a stable adenosine analogue, L-N6-phenylisopropyladenosine (L-PIA, 0.3 mg/kg i. p.), caused a decrease in the accumulation of L-DOPA in the rat hippocampus after blockade of aromatic amino acid decarboxylase by NSD 1015 (150 mg/kg). Conversely, the adenosine receptor antagonist theophylline (15 mg/kg) increased the L-DOPA accumulation. In slices from rat hippocampus L-PIA causes an inhibition of the stimulation-evoked release of [3H]-noradrenaline (NA). The magnitude of this effect was enhanced after 1 week treatment with theophylline (15 mg/kg/day). The number of beta-adrenoceptors in the rat hippocampus, measured by binding of [3H]-dihydroalprenolol was significantly reduced after theophylline treatment, and tended to be higher after L-PIA treatment. The results show that activation of adenosine receptors in vivo causes a decreased synthesis of NA in the rat hippocampus. The reason may be a reduced firing-rate of the NA-neurons. Theophylline, by contrast, enhanced the synthesis, possibly indicating a role for endogenous adenosine in the regulation of NA-turnover. Long-term treatment with these drugs caused adaptive changes in the presynaptic adenosine receptor activity and in the number of beta-adrenoceptors.
D000222:Adaptation, Physiological / Q000187:drug effects; D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011983:Receptors, Purinergic; D013806:Theophylline / Q000494:pharmacology*; D013997:Time Factors
D011943:Receptors, Adrenergic, beta; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D004082:Dihydroalprenolol; D013806:Theophylline; D000241:Adenosine; D009638:Norepinephrine