Neurotensin and dopamine D2 activation oppositely regulate the same K+ conductance in rat midbrain dopaminergic neurons.

Midbrain dopaminergic neurons are excited by neurotensin (NT) and inhibited by dopamine. Interactions between these neurotransmitters have been reported, but no interaction has yet been identified at the level of ionic and signal transduction mechanisms. Using the whole-cell clamp technique, we examined the interaction of NT and quinpirole (QUIN) (a dopamine D2 agonist) on midbrain ventral tegmental area neurons cultured from the rat. We found that NT could inhibit the K+ conductance induced by QUIN. By interrupting normal signal transduction with the non-hydrolyzable GTP analogue GTPgammaS, we found that this interaction occurred downstream of the membrane neurotransmitter receptors. Similar interactions were observed between QUIN and tachykinin or metabotropic glutamate agonists.