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Titolo:
6-HYDROXYDOPAMINE LESIONS OF RAT SUBSTANTIA-NIGRA UP-REGULATE DOPAMINE-INDUCED PHOSPHORYLATION OF THE CAMP-RESPONSE ELEMENT-BINDING PROTEININ STRIATAL NEURONS
Autore:
COLE DG; KOBIERSKI LA; KONRADI C; HYMAN SE;
Indirizzi:
MASSACHUSETTS GEN HOSP E,MOLEC & DEV NEUROSCI LAB BOSTON MA 02129 MASSACHUSETTS GEN HOSP E,DEPT NEUROL BOSTON MA 02129 MASSACHUSETTS GEN HOSP E,DEPT PSYCHIAT BOSTON MA 02129
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 20, volume: 91, anno: 1994,
pagine: 9631 - 9635
SICI:
0027-8424(1994)91:20<9631:6LORSU>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHOLINERGIC RECEPTOR SUBTYPES; CENTRAL PATHOPHYSIOLOGICAL MECHANISMS; PARKINSONS-DISEASE; C-FOS; DIFFERENTIAL RESPONSE; MOTOR FLUCTUATIONS; SODIUM-CHANNELS; MOLECULAR-CLONING; ADENYLYL CYCLASE; CALCIUM CHANNELS;
Keywords:
[SER(P)(133)]CREB; D1 DOPAMINE RECEPTOR SUPERSENSITIVITY; CAMP-DEPENDENT PROTEIN KINASE; CA2+; CALMODULIN-DEPENDENT PROTEIN KINASE; FOS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
57
Recensione:
Indirizzi per estratti:
Citazione:
D.G. Cole et al., "6-HYDROXYDOPAMINE LESIONS OF RAT SUBSTANTIA-NIGRA UP-REGULATE DOPAMINE-INDUCED PHOSPHORYLATION OF THE CAMP-RESPONSE ELEMENT-BINDING PROTEININ STRIATAL NEURONS", Proceedings of the National Academy of Sciences of the United Statesof America, 91(20), 1994, pp. 9631-9635

Abstract

Destruction of the substantia nigra produces striatal D1 dopamine receptor supersensitivity without increasing receptor number or affinity,thus implicating postreceptor mechanisms. The nature of these mechanisms is unknown. Increased striatal c-fos expression ipsilateral to a unilateral lesion of the substantia nigra in rats treated with appropriate dopamine agonists provides a cellular marker of D1 receptor supersensitivity. D1 receptors are positively linked to adenylate cyclase and therefore to cAMP-dependent protein kinase. Because expression of the c-fos gene in response to cAMP- and Ca2+/calmodulin-regulated protein kinases depends on phosphorylation of cAMP response element-binding protein (CREB) at Ser-133, we examined CREB phosphorylation after dopaminergic stimulation in cultured striatal neurons and in the striatum of rats after unilateral 6-hydroxydopamine ablation of the substantia nigra. Using an antiserum specific for CREB phosphorylated at Ser-133,we found that dopamine increases CREB phosphorylation in cultured striatal neurons. This effect was blocked by a D1 antagonist. L-Dopa produced marked CREB phosphorylation in striatal neurons in rats ipsilateral, but not contralateral, to a 6-hydroxydopamine lesion. This response was blocked by a D1 antagonist, but not a D2 antagonist, and was reproduced by a D1 agonist, but not a D2 agonist. These findings are consistent with the hypothesis that D1 receptor supersensitivity is associated with upregulated activity of cAMP-dependent or Ca2+/calmodulin-dependent protein kinases, or both, following dopamine denervation of striatal neurons.

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Documento generato il 08/04/20 alle ore 08:56:43