PROPERTIES OF 3,4-DIAMINOPYRIDINE-EVOKED DOPAMINE AND ACETYLCHOLINE-RELEASE IN RABBIT CAUDATE-NUCLEUS SLICES - INVOLVEMENT OF FACILITATORY ADENOSINE A(2) RECEPTORS OR NITRIC-OXIDE

The H-3-overflow from slices of the rabbit caudate nucleus preincubate d with tritiated dopamine (DA), or choline, and then superfused and st imulated twice with 3,4-diaminopyridine (3,4-DAP; 25 mu M, 1 min), was explored as an in vitro model for evoked release of DA, or acetylchol ine (ACh), respectively. In both cases the 3,4-DAP-evoked H-3-overflow was tetrodotoxin-sensitive and Ca2+-dependent and hence most probably represents action potential-induced exocytotic release of DA or ACh, respectively. Using pairs of preferential agonists/antagonists it was shown, that evoked DA release was inhibited via presynaptic D-2 autore ceptors (quinpirole/domperidone) and kappa-opioid receptors (U-50488H/ norbinaltorphimine). No evidence was found for the presence of presyna ptic adenosine A(1) or A(2) receptors on dopaminergic terminals. Moreo ver, 3,4-DAP-evoked DA release was unaffected by increased intracellul ar cyclic AMP levels or by drugs affecting the NO/guanylate cyclase pa thway. In a similar manner it was shown that 3,4-DAP-evoked ACh releas e was inhibited via presynaptic muse arine autoreceptors (oxotremorine /atropine) and dopamine D-2 heteroreceptors (quinpirole/domperidone). Again, no evidence for the involvement of the NO/guanylate cyclase sys tem in the modulation of ACh release was found, whereas the presence o f inhibitory adenosine A(1) receptors, but not of facilitatory A(2) re ceptors, could be clearly established. It is concluded, that 3,4-DAP-e voked H-3-overflow from rabbit caudate nucleus slices preincubated wit h [H-3]DA or [H-3]choline, represents a simple and useful in vitro mod el for action potential-induced DA or ACh release, respectively. Moreo ver, at least in this model or rabbit brain region, facilitatory adeno sine A(2) receptors and the NO/guanylate cyclase system seem not to be involved in the release of these transmitters.