1 Some postganglionic sympathetic axons possess P2Y-like P2-purinoceptors which, when activated, decrease the release of noradrenaline. We examined the question of whether such receptors also occur at the noradrenergic axons in the rat brain cortex. Slices of the brain cortex were preincubated with pH]-noradrenaline, then superfused with medium containing desipramine (1 gM) and stimulated electrically, in most experiments by trains of 4 pulses/100 Hz.2 The selective adenosine Al-receptor agonist, N6-cyclopentyl-adenosine (CPA; 0.03-3 gM) as well as the non-subtype-selective agonist 5'-N-ethylcarboxamido-adenosine (NECA; 0.3-3 EM) reduced the evoked overflow of tritium, whereas the adenosine A2.-receptor agonist, 2-p-(2-carbonylethyl)-phenethylamino-5'-N-ethylcarboxamido-adenosine (CGS-21680; 0.003-30;LM) and the adenosine A3-receptor agonist N6-2-(4-aminophenyl)ethyl-adenosine (APNEA; 0.03-31M) caused no change. Of the nucleotides tested, ATP (30-300 JM), adenosine-5'-O-(3-thiotriphosphate) (ATPyS; 30-300 pM), adenosine-5'-O-(2-thiodiphosphate) (ADPPS; 30-300ILM), P1,P4-di(adenosine-5')-tetraphosphate (Ap4A; 30-3001LM) and the preferential P2Y-purinoceptor agonist, 2-methylthio-ATP (300 tM) decreased the evoked overflow of tritium. The P' -purinoceptor agonist, a,-methylene-ATP (3-3001fM) caused no change.3 The Al-selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 10 nM) attenuated the effects of the nucleosides CPA (apparent pKB value 9.8) and NECA as well as of the nucleotides ATP (apparent pKB 9.3), ATPyS (apparent pKB 9.2) and ADPBS (apparent pKB 8.7). CGS-21680 and APNEA were ineffective also in the presence of DPCPX. The A2-selective antagonist 1,3-dipropyl-8-(3,4-dimethoxystyryl)-7-methylxanthine (KF-17837) reduced the effects of CPA, NECA and ATPyS only when given at a concentration of 300 nM but not at 1O nM. 4 The P2-purinoceptor antagonists, suramin (300 ,M), reactive blue 2 (30 1M) and cibacron blue 3GA (301M) did not change the effect of CPA. Suramin and cibacron blue 3GA shifted the concentrationresponse curve of ATPyS to the right (apparent pKB values 3.7 and 5.0, respectively). Reactive blue 2 also attenuated the effect of ATPyS, and cibacron blue 3GA attenuated the effect of ATP, but in these cases the agonist concentration-response curves were not shifted to the right. There was no antagonistic effect of suramin against ATP and ADPPS. 5 The results indicate that rat cerebrocortical noradrenergic axons possess, in addition to the known adenosine Al-receptor, a separate purinoceptor for nucleotides (P2) which, in contrast to the Al-receptor, is blocked by suramin, reactive blue 2 and cibacron blue 3GA. Nucleotides such as ATP and ATPyS activate both receptors. Inconsistencies in antagonist effects against nucleotides are probably due to this activation of two receptors. The presynaptic P2-purinoceptor is P2Y-like, as it is in the peripheral sympathetic nervous system. Keywords: Rat brain cortex; PI-purinoceptor; P2-purinoceptor; presynaptic purinoceptors; noradrenaline release; ad...