Presynaptic opioid receptors on dopaminergic nerves in the rabbit caudate nucleus: coupling to pertussis toxin-sensitive G-proteins and interaction with D2 autoreceptors?

Abstract

Slices of the rabbit caudate nucleus, preincubated with [3H]dopamine and subjected to electrical field stimulation, were used (1) to investigate the involvement of G-proteins in the signal transduction of presynaptic D2 (auto)receptors and kappa-opioid receptors on dopaminergic axon terminals in this tissue and (2) to study a possible mutual interaction of these two presynaptic receptors. Pretreatment of the slices with either pertussis toxin (8 micrograms/ml; 18 h), or N-ethylmaleimide (30 microM, 30 min) significantly reduced the inhibitory effects of both the D2 agonist quinpirole and the kappa-opioid receptor agonist U-50488H on the [3H]overflow evoked by 36 pulses (2 ms, 24 mA, 0.3 Hz), suggesting the coupling of both receptors to G-proteins. Experiments designed to study possible interactions of these two presynaptic receptors were carried out under stimulation conditions (only 1 pulse), which strongly diminish interference of endogenous transmitters released in the tissue with modulatory effects of exogenous drugs. For instance, due to the presence of endogenous dopamine, quinpirole was much less potent during 36-pulse-than during 1-pulse field stimulation, whereas the D2 antagonist domperidone was almost without effect in the latter case. Using the 1-pulse stimulation paradigm, the concentration/response curve of quinpirole was unaffected in the presence of the half-maximal inhibitory concentration of U-50,488 H (0.1 microM). On the other hand, also quinpirole at its half-maximal inhibitory concentration (0.1 microM), hardly affected the concentration/response curve of U-50,488 H: only high concentrations of U-50,488 H (above 1 microM) seemed to be slightly less effective in the presence than in the absence of the D2 agonist.(ABSTRACT TRUNCATED AT 250 WORDS)