Inhibition of nigrostriatal release of dopamine in the rat by adenosine receptor agonists: A1 receptor mediation.
The stable analogues of adenosine, N-ethylcarboxamidoadenosine (NECA), R-phenylisopropyladenosine (R-PIA) and cyclohexyladenosine (CHA), dose-dependently decreased levels of 3-methoxytyramine (3-MT) in the striatum and antagonized pargyline-dependent accumulation of 3-methoxytyramine. These agents were equipotent with ED25 values of approximately 1 mg/kg, (p.o.) in inhibiting pargyline-dependent accumulation of 3-methoxytyramine. Since CHA and R-PIA are relatively selective for A1 receptors and NECA is almost equipotent at A1 and A2 sites, the data of undifferentiated potency for these 3 agents on release of dopamine (levels of 3-MT) would argue in favor of mediation of A1 receptors in this phenomenon. This conclusion was further supported by experiments with the A1-selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPDX), which antagonized the actions of CHA. Similar antagonism of CHA-dependent decreases in levels of cyclic GMP in the cerebellum, an action known to be mediated by A1 receptors, was also observed. These data support previous studies which indicated an adenosine receptor-mediated modulation of nigrostriatal release of dopamine. In addition, the present data indicate that this is an action on A1 receptors.
Wood
P L
PL
Research Department, Ciba-Geigy Corporation, Summit, New Jersey 07901.
Kim
H S
HS
Boyar
W C
WC
Hutchison
A
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000032:analysis; D003342:Corpus Striatum / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D018492:Dopamine Antagonists; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000502:physiology
D018492:Dopamine Antagonists; D011506:Proteins; D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D006152:Cyclic GMP; C001746:3-methoxytyramine; D000241:Adenosine; D004298:Dopamine