PRESYNAPTIC OPIOID RECEPTORS ON DOPAMINERGIC NERVES IN THE RABBIT CAUDATE-NUCLEUS - COUPLING TO PERTUSSIS-TOXIN-SENSITIVE G-PROTEINS AND INTERACTION WITH D-2 AUTORECEPTORS

Slices of the rabbit caudate nucleus, preincubated with [H-3]dopamine and subjected to electrical field stimulation, were used (1) to invest igate the involvement of G-proteins in the signal transduction of pres ynaptic D-2 (auto)receptors and kappa-opioid receptors on dopaminergic axon terminals in this tissue and (2) to study a possible mutual inte raction of these two presynaptic receptors. Pretreatment of the slices with either pertussis toxin (8 mu g/ml; 18 h), or N-ethylmaleimide (3 0 mu M, 30 min) significantly reduced the inhibitory effects of both t he D-2 agonist quinpirole and the kappa-opioid receptor agonist U-5048 8H on the [H-3]overflow evoked by 36 pulses (2 ms, 24 mA, 0.3 Hz), sug gesting the coupling of both receptors to G-proteins. Experiments desi gned to study possible interactions of these two presynaptic receptors were carried out under stimulation conditions (only 1 pulse), which s trongly diminish interference of endogenous transmitters released in t he tissue with modulatory effects of exogenous drugs. For instance, du e to the presence of endogenous dopamine, quinpirole was much less pot ent during 36-pulse-than during 1-pulse field stimulation, whereas the D-2 antagonist domperidone was almost without effect in the latter ca se. Using the 1-pulse stimulation paradigm, the concentration/response curve of quinpirole was unaffected in the presence of the halfmaximal inhibitory concentration of U-50,488 H (0.1 mu M). On the other hand, also quinpirole at its halfmaximal inhibitory concentration (0.1 mu M ), hardly affected the concentration/response curve of U-50,488 H: onl y high concentrations of U-50,488 H (above 1 mu M) seemed to be slight ly less effective in the presence than in the absence of the D-2 agoni st. U-50,488 H, at these high concentrations, was also less potent und er 36-pulse than under 1-pulse stimulation conditions. From these find ings, we conclude that there is only a limited interaction between pre synaptic D-2 autoreceptors and kappa-opioid receptors on dopaminergic axon terminals in the rabbit caudate nucleus, despite they are both co upled to PTX/NEM-sensitive G-proteins.