Co-transmitter function of ATP in central catecholaminergic neurons of the rat

• Published in: Neuroscience 2001-01, Vol.102 (3), p.593-602
• Main Authors: Poelchen, W, Sieler, D, Wirkner, K, Illes, P
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - analogs & derivatives; Adenosine Diphosphate - pharmacology; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Adenosine Triphosphate - physiology; Animals; Biological and medical sciences; Catecholamines - physiology; Central nervous system; co-transmission; Electric Stimulation; Electrophysiology; Evoked Potentials - drug effects; Evoked Potentials - physiology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Fundamental and applied biological sciences. Psychology; Guanethidine - pharmacology; Idazoxan - pharmacology; In Vitro Techniques; Kynurenic Acid - pharmacology; locus coeruleus neurons; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Neurons - drug effects; Neurons - physiology; noradrenaline; Norepinephrine - pharmacology; Oxidopamine - pharmacology; Picrotoxin - pharmacology; Pons - physiology; Pyridoxal Phosphate - analogs & derivatives; Pyridoxal Phosphate - pharmacology; Rats; Rats, Wistar; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Thionucleotides - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(00)00529-7

Intracellular recordings were made in a mid-pontine slice preparation of the rat brain containing the nucleus locus coeruleus. Focal electrical stimulation evoked biphasic synaptic potentials consisting of early depolarizing (d.p.s.p.) and late hyperpolarizing (i.p.s.p.) components. The α 2-adrenoceptor antagonist idazoxan inhibited the i.p.s.p. without altering the d.p.s.p. All of the following experiments were carried out in the presence of kynurenic acid and picrotoxin to block the glutamatergic and GABAergic fractions of the d.p.s.p., respectively. Guanethidine, which is known to inhibit noradrenaline and ATP release from nerve terminals of postganglionic sympathetic nerves, depressed both the d.p.s.p. and the i.p.s.p. in a concentration-dependent manner. Damage of catecholaminergic nerve terminals by 6-hydroxydopamine also decreased both the d.p.s.p. and the i.p.s.p. The P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS) depressed the d.p.s.p., whereas the i.p.s.p. remained unaffected. The further application of PPADS did not increase the depression of the d.p.s.p. by guanethidine. Superfusion with the mixed α-adrenoceptor agonist noradrenaline or the selective P2 receptor agonist adenosine 5′- O-(2-thiodiphosphate) inhibited both the d.p.s.p. and the i.p.s.p. The inhibitory effects of these agonists were prevented by the respective antagonists idazoxan or suramin. In the presence of suramin noradrenaline failed to inhibit the residual d.p.s.p. Superfused noradrenaline potentiated rather than inhibited responses to pressure-applied α,β-methylene-ATP; superfused adenosine 5′- O-(2-thiodiphosphate) did not interact with pressure-applied noradrenaline. In conclusion, we present electrophysiological evidence for the co-release of ATP and catecholamines in the CNS. At the cell somata of neurons in the locus coeruleus, noradrenaline and ATP activate inhibitory α 2-adrenoceptors and excitatory P2 receptors, respectively. In addition, inhibitory presynaptic autoreceptors of the α 2 and P2 types appear to regulate release of the two co-transmitters.