The effects of dopamine D1 and D2 receptors agonists, give alone or jontly with a nitric oxide donor, on expression of proteins involved in the nitrergic signaling and on cGMP production in 6-OHDA-lesioned rats

BACKGROUND AND AIMS: The aim of the present study was to examine the effects of selective dopamine (DA) D1 and D2 receptors agonists administered chronically, alone or in combination with the nitric oxide donor molsidomine on expression of proteins involved in the nitric oxide – soluble guanylyl cyclase – cGMP signaling pathway and on the cGMP levels in the striatum (STR) of 6-OHDA-lesioned rats. METHODS:Two weeks after unilateral injection of 6-OHDA(8 µg/4 µl) into the medial forebrain bundle, rats were treated chronically (15 days) with DA D1 (SKF38393; 3 mg/kg sc) or DA D2 (quinpirole 0.2 mg/kg sc) receptor agonists and molsidomine (2 mg/kg ip), alone and in combination. The contents of neuronal nitric oxide synthase (nNOS), sGC and phosphodiesterase 1B (PDE-1B) proteins were determined in the STR by Western blot technique while cGMP level using competitive enzyme immunoassay cGMP kit. RESULTS: In the ipsilateral STR chronic treatment with SKF38393 alone or jointly with molsidomine did not affect nNOS protein level. Quinpirole alone had no effect on nNOS level while given jointly with molsidomine decreased it markedly. Both SKF38393 and quinpirole alone did not change sGC protein level in the ipsilateral STR while their joint administration with molsidomine enhanced it markedly. SKF38393 and quinpirole alone decreased PDE-1B protein expression but only combined administration of quinpirole + molsidomine enhanced the content of this protein. As to cGMP level, chronic treatment with molsidomine alone increased cGMP concentration in the ipsi- and contralateral STR. SKF38393 administered chronically alone or jointly with molsidomine enhanced cGMP content only in the ipsilateral STR while quinpirole alone or in combination with molsidomine did not evoke such effects. CONCLUSION: The obtained results suggest that the treatment with selective DA D1 and D2 agonists differently modulates the NO-sGC-cGMP signaling pathway in 6-OHDA-lesioned rats.