Inhibition of Purkinje cell firing by systemic administration of phenylisopropyl adenosine: effect of central noradrenaline depletion by DSP4.
The effect of the metabolically stable adenosine analog (-)-N6(R-phenyl-isopropyl)-adenosine (PIA) on the rate of spontaneous Purkinje cell firing was studied in anesthetized rats. In control animals, systemically administered PIA elicited only small and inconsistent changes in firing rate. However, in animals previously treated with DSP4 (50 mg/kg i.p.), which selectively lesions central noradrenergic afferents, or with the adrenergic antagonist sotalol (15 mg/kg), PIA elicited consistent decreases in firing rate. These effects were antagonized by the systemic administration of the adenosine receptor antagonist aminophylline (50-150 mumol/kg). Local administration of adenosine by pressure ejection caused a dose-dependent depression of Purkinje cell firing that was likewise inhibited by the methylxanthine. In DSP4 treated rats the depression of synaptic transmission by adenosine in rat hippocampus in vitro was unaltered, and theophylline did not cause any marked rise in Purkinje cell firing, suggesting that DSP4 does not sensitize neurons to the depressant effects of adenosine derivatives. PIA also caused a dose-dependent decrease in arterial blood pressure and a decrease in heart rate that was of equal magnitude in control and DSP4 treated rats. The results show that the central effects of systemically administered adenosine analogs are altered by procedures that disrupt the normal depressant effect of tonic noradrenergic input.
Bickford
P C
PC
Fredholm
B B
BB
Dunwiddie
T V
TV
Freedman
R
R
D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000588:Amines / Q000494:pharmacology*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011983:Receptors, Purinergic
D000588:Amines; D001596:Benzylamines; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D000628:Aminophylline; D010660:Phenylisopropyladenosine; D000241:Adenosine; C012102:DSP 4