Nitric oxide (NO) can differentially modulate striatal dopaminergic activity. We showed previously 1 that the extracellular NO-donors sodium nitroprusside and 3-morfolinosydnonimine increased DA concentration in dialysates from the striatum of freely moving rats. In this study, the effects on dopamine metabolism of the intracellular NO donor hydroxylamine were evaluated in the striatum of freely moving rats, using microdialysis, and in PC12 cells. When infused intrastriatally, hydroxylamine (1 or 5 mM for 180 min, n=4/group)) decreased dialysate DA (baseline levels 4.81±1.26 and 3.86±0.55 nM, respectively) and ascorbic acid (AA) concentrations (baseline levels 7.58±0.37 and 8.35±1.01 μM, respectively); in contrast, dialysate DOPAC concentrations (baseline levels 2.08±0.38 and 1.79±0,23 μM, respectively) were unaffected, while those of L-DOPA(baseline levels 2.21±0.42 and 1.88±0.33 mM, respectively) were significantly increased. Co-infusion of AA or Nacetylcysteine (NAC) failed to antagonise hydroxylamine-induced decreases in dialysate DA. In PC12 cells cultures, hydroxylamine induced a concentration-related decrease of cell viability; in addition, hydroxylamine decreased tissue concentration of both DA (control values 8.36±0.34 nmol/mg protein, n=3) and DOPAC (control values 0.33±0.05 nmol/mg protein, n=3). Taken together, these results suggest that excess of NO formed intraneuronally can inhibit dopaminergic transmission by increasing DA non-enzymatic oxidation and inhibiting L-DOPA conversion to DA. This conclusion is supported by the finding (unpublished observation) that intrastriatal infusion of 7-nitroindazole (a neuronal NO sinthase inhibitor) significantly increased dialysate concentrations of DA, DOPAC and AA.
EFFECTS OF HYDROXYLAMINE ON DOPAMINE METABOLISM IN THE STRIATUM OF FREELY MOVING RATS AND IN PC12 CELLS / Migheli, Rossana; Rocchitta, Gaia Giovanna Maria; M. G., Taras; E., Miele; Serra, Pier Andrea; Desole, Maria Speranza; M. R., Delogu. - (2001). (Intervento presentato al convegno XXX Congresso Nazionale della Società Italiana di Farmacologia tenutosi a Genova nel 30 Maggio – 2 Giugno 2001).
EFFECTS OF HYDROXYLAMINE ON DOPAMINE METABOLISM IN THE STRIATUM OF FREELY MOVING RATS AND IN PC12 CELLS
MIGHELI, Rossana;ROCCHITTA, Gaia Giovanna Maria;SERRA, Pier Andrea;DESOLE, Maria Speranza;
2001-01-01
Abstract
Nitric oxide (NO) can differentially modulate striatal dopaminergic activity. We showed previously 1 that the extracellular NO-donors sodium nitroprusside and 3-morfolinosydnonimine increased DA concentration in dialysates from the striatum of freely moving rats. In this study, the effects on dopamine metabolism of the intracellular NO donor hydroxylamine were evaluated in the striatum of freely moving rats, using microdialysis, and in PC12 cells. When infused intrastriatally, hydroxylamine (1 or 5 mM for 180 min, n=4/group)) decreased dialysate DA (baseline levels 4.81±1.26 and 3.86±0.55 nM, respectively) and ascorbic acid (AA) concentrations (baseline levels 7.58±0.37 and 8.35±1.01 μM, respectively); in contrast, dialysate DOPAC concentrations (baseline levels 2.08±0.38 and 1.79±0,23 μM, respectively) were unaffected, while those of L-DOPA(baseline levels 2.21±0.42 and 1.88±0.33 mM, respectively) were significantly increased. Co-infusion of AA or Nacetylcysteine (NAC) failed to antagonise hydroxylamine-induced decreases in dialysate DA. In PC12 cells cultures, hydroxylamine induced a concentration-related decrease of cell viability; in addition, hydroxylamine decreased tissue concentration of both DA (control values 8.36±0.34 nmol/mg protein, n=3) and DOPAC (control values 0.33±0.05 nmol/mg protein, n=3). Taken together, these results suggest that excess of NO formed intraneuronally can inhibit dopaminergic transmission by increasing DA non-enzymatic oxidation and inhibiting L-DOPA conversion to DA. This conclusion is supported by the finding (unpublished observation) that intrastriatal infusion of 7-nitroindazole (a neuronal NO sinthase inhibitor) significantly increased dialysate concentrations of DA, DOPAC and AA.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
