A single dose of the D1 agonist SKF 38393 (3 mg/kg) produces contralateral turning in unilaterally 6-hydroxydopamine lesioned rats only after a previous exposure of the animals to a dopamine agonist. This priming phenomenon is here investigated by studying the phosphorylation of DARPP-32, a dopamine- and cyclic AMP-regulated phosphoprotein functionally linked to D1 receptors in striatum. Dephospho-form of DARPP-32 in striatal tissue was measured by a back-phosphorylation assay. While the levels of DARPP-32 protein, as measured by quantitative immunoblotting, remained unchanged, a significant decrease of dephospho-DARPP-32 was observed in the denervated striatum of primed rats, indicating an increased phosphorylation in vivo of DARPP-32 in response to the D1 agonist. This study shows that an alteration of the dopamine-dependent signal transduction is related to the behavioral response to dopamine agents, suggesting a possible mechanism involved in the effects of these drugs in parkinsonian patients.

Dopamine mediated responses in 6-hydroxydopamine lesioned rats involve changes of the signal transduction / P. Barone, M. Popoli, M. Morelli, G. Cicarelli, G. Campanella, G. DiChiara. - In: JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT. - ISSN 0303-6995. - :45(1995), pp. 83-90. ((Intervento presentato al 1. convegno 1st International Congress on Dopamine Agonists tenutosi a Pisa, ITALY nel 1993.

Dopamine mediated responses in 6-hydroxydopamine lesioned rats involve changes of the signal transduction

M. Popoli
Secondo
;
1995

Abstract

A single dose of the D1 agonist SKF 38393 (3 mg/kg) produces contralateral turning in unilaterally 6-hydroxydopamine lesioned rats only after a previous exposure of the animals to a dopamine agonist. This priming phenomenon is here investigated by studying the phosphorylation of DARPP-32, a dopamine- and cyclic AMP-regulated phosphoprotein functionally linked to D1 receptors in striatum. Dephospho-form of DARPP-32 in striatal tissue was measured by a back-phosphorylation assay. While the levels of DARPP-32 protein, as measured by quantitative immunoblotting, remained unchanged, a significant decrease of dephospho-DARPP-32 was observed in the denervated striatum of primed rats, indicating an increased phosphorylation in vivo of DARPP-32 in response to the D1 agonist. This study shows that an alteration of the dopamine-dependent signal transduction is related to the behavioral response to dopamine agents, suggesting a possible mechanism involved in the effects of these drugs in parkinsonian patients.
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/187952
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