Co-transmitter function of ATP in central catecholaminergic neurons of the rat.
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 alpha(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 alpha-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 alpha,beta-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 alpha(2)-adrenoceptors and excitatory P2 receptors, respectively. In addition, inhibitory presynaptic autoreceptors of the alpha(2) and P2 types appear to regulate release of the two co-transmitters.
Poelchen
W
W
Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, Härtelstrasse 16-18, D-04107, Leipzig, Germany.
Sieler
D
D
Wirkner
K
K
Illes
P
P
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002395:Catecholamines / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D006145:Guanethidine / Q000494:pharmacology; D019329:Idazoxan / Q000494:pharmacology; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011149:Pons / Q000502:physiology*; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002395:Catecholamines; D006145:Guanethidine; D019329:Idazoxan; D007736:Kynurenic Acid; D009638:Norepinephrine; D016627:Oxidopamine; D010852:Picrotoxin; D011732:Pyridoxal Phosphate; D013873:Thionucleotides; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C030812:adenosine 5'-O-(2-thiodiphosphate); C002630:alpha,beta-methyleneadenosine 5'-triphosphate