NITRIC-OXIDE INVOLVEMENT IN REGULATING THE DOPAMINE TRANSPORT IN THE STRIATAL REGION OF RAT-BRAIN

Spontaneous [H-3]dopamine ([H-3]DA) overflow was measured from striata l slices in the presence of different glutamate (Glu) receptor agonist s such as N-methyl-D-aspartate (NMDA), kainate (KA) and quisqualate (Q A) and their corresponding antagonists, Dizocilpine maleate (MK-801), D-gamma-glutamylaminomethanesulfonic acid (GAMS) and 6-cyano-7-nitroqu inoxaline 2,3-dione (CNQX), respectively. [H-3]DA uptake and release i n the presence of L-Arginine (L-Arg) and N-G-nitro-arginine (L-N-Arg), an inhibitor of nitric oxide (NO) synthesis were also evaluated. L-N- Arg alone or combined with L-Arg significantly reduced [H-3]DA uptake at 10 and 100 mu M from 33% to 44% from striatal slices. Whereas, in b rain synaptosomal fractions L-Arg induced a biphasic effect on that [H -3]DA uptake in a dose dependent manner, and L-N-Arg showed an absolut e inhibition in 80-90% of this [H-3]DA uptake at 1-500 mu M. The amino acids, lysine, valine and histidine (100 mu M) had a little effect in hibitory on [H-3]DA uptake from synaptosomal fractions. Glu agonists, NMDA (10 mu M) and KA (10 mu M) importantly increased the spontaneous [H-3]DA overflow, which was blocked by MK-801 (10 mu M) and GAMS (10 m u M), respectively. QA had no effect on [H-3]DA release. L-Arg (10-200 mu M) potentiated the spontaneous [H-3]DA overflow in a dose dependen t fashion from striatal slices, being reverted by 10 mu M L-N-Arg alon e or in combination with all other compounds; whereas, lysine, histidi ne and valine did not modify that spontaneous [H-3]DA overflow. Result s support the hypothesis related to the participation of NO on DA tran sport possibly synthesized at the dopaminergic (DAergic) terminals in the striatum; also that L-Arg concentration may determine alternative mechanisms to regulate the DAergic activity at the striatum. (C) 1997 Elsevier Science Ltd.