Intracellular recordings were made in a mid-pontine slice preparation of th
e rat brain containing the nucleus locus coeruleus. Focal electrical stimul
ation evoked biphasic synaptic potentials consisting, of early depolarizing
(d.p.s.p.) and late hyperpolarizing (i.p.s.p.) components. The alpha (2)-a
drenoceptor 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 in
hibit 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 conce
ntration-dependent manner. Damage of catecholaminergic nerve terminals by 6
-hydroxydopamine also decreased both the d.p.s.D. and the i.p.s.p. The P2 r
eceptor antagonist pyridoxal-phosphate-6-azophenyl-2 ' ,4 ' -disulphonic ac
id (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 cl-adrenoceptor agonist
noradrenaline or the selective P2 receptor agonist adenosine 5 ' -O-(2-thi
odiphosphate) inhibited both the d.p.s.p. and the i.p.s.p. The inhibitory e
ffects of these agonists were prevented by the respective antagonists idazo
xan or suramin. In the presence of suramin noradrenaline failed to inhibit
the residual d.p.s.p. Superfused noradrenaline potentiated rather than inhi
bited responses to pressure-applied alpha,beta -methylene-ATP; superfused a
denosine 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 cocrulcus, noradrenaline and ATP activate inhibitory az-adrenoceptors
and excitatory P2 receptors, respectively. In addition, inhibitory presyna
ptic autoreceptors of the alpha (2) and P2 types appear to regulate release
of the two co-transmitters. (C) 2001 IBRO. Published by Elsevier Science L
td. All rights reserved.