Dopamine activates adenylyl cyclase via D1 receptors and inhibits
activity by D2. 6-OHDA, a neurotoxin, results in cell atrophy and
increased dopamine signaling in surviving neurons, at least in the
nigrostriatal pathway. Cause or effect in CR?

Biochem Pharmacol. 1992 Jul 7;44(1):73-82.  Related Articles, Links  

Dissociation of the striatal D-2 dopamine receptor from adenylyl
cyclase following 6-hydroxydopamine-induced denervation.

Thomas KL, Rose S, Jenner P, Marsden CD.

Parkinson's Disease Society Experimental Research Laboratories, King's
College London, U.K.

Intracellular cyclic AMP accumulation following exposure to dopamine
(DA) agonists and and antagonists was measured in striatal slices from
rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the
nigrostriatal pathway and which showed contralateral circling to
apomorphine. Both DA (10-320 microM) and the D-1 agonist SKF 38393
(0.1-32 microM) increased cyclic AMP accumulation in striatal slices
from the lesioned and intact hemispheres. The EC50 for DA to increase
cyclic AMP accumulation in slices was greater in the 6-OHDA-lesioned
striata compared to the intact striatum, but the EC50 for SKF 38393
was not affected. The D-1 antagonist SCH 23390 (10 microM) completely
inhibited the ability of DA and SKF 38393 to increase cyclic AMP
accumulation in striatal slices from both denervated and intact sides
of the brain. In slices from the intact hemisphere the increase in
DA-induced cyclic AMP accumulation was enhanced by the D-2 antagonist
(+/-)-sulpiride (50 microM) but (+/-)-sulpiride had no effect on the
DA response in slices from the lesioned side. Similarly, the ability
of SKF 38393 to enhance cyclic AMP accumulation was blocked by the D-2
agonist quinpirole (10 microM) in striatal slices from the intact
hemisphere but not in tissue from the lesioned side. The density of
striatal D-1 and D-2 receptors assessed by [3H]SCH 23390 and
[3H]spiperone binding did not differ between the hemispheres although
there was an increase in the affinity of D-1 receptors for [3H]SCH
23390 in the lesioned striatum. After striatal deafferentiation there
appears to be an uncoupling of the "inhibitory" D-2 receptor from the
D-1 receptor-associated adenylyl cyclase.

PMID: 1321630 [PubMed - indexed for MEDLINE]

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