P2-RECEPTOR-MEDIATED INHIBITION OF SEROTONIN RELEASE IN THE RAT-BRAINCORTEX

The possibility of a P2-receptor-mediated modulation of the release of serotonin in the rat brain cortex was investigated in occipito-pariet al slices preincubated with [H-3]serotonin and then superfused and sti mulated electrically (10 pulses, 1 Hz). Adenosine receptor agonists de creased the stimulation-evoked overflow of tritium at best slightly; t he selective A(1) agonist N-6-cyclopentyl-adenosine caused no change. Several nucleotides had more marked effects: ATP (3-1000 mu M), adenos ine-5'-O-(3-thiotriphosphate) (3-300 mu M) and P-1,P-5-di(adenosine-5' )-pentaphosphate (3-300 mu M) decreased the evoked overflow by up to c a 35%. AMP, alpha,beta-methylene-ATP and UTP produced smaller decrease s and 2-methylthio-ATP and UMP caused no change. The inhibition by ATP was attenuated both by the P1-receptor antagonist 8-(p-sulphophenyl)- theophylline (100 mu M) and by the P2-receptor antagonist suramin (300 mu M) but was not changed by indomethacin (10 mu M) and N-G-nitro-L-a rginine (10 mu M). We conclude that the release of serotonin in the ra t brain cortex is inhibited through presynaptic P1-receptors (which ar e not A(1)) as well as P2-receptors. Inhibition of release via P2-rece ptors has been previously shown for noradrenaline (brain cortex and hi ppocampus) and dopamine (neostriatum) and, hence, may be widespread. D ifferences between transmitter systems exist, however, in the degree o f their sensitivity to presynaptic P2-receptor-mediated modulation. (C ) 1997 Elsevier Science Ltd.