Evidence for the existence of two distinct dopamine D-2 receptors in presynaptic nerve terminals from rat corpus striatum

1 Radioactive rubidium (86Rb+) efflux was used to measure potassium (K+) permeability in a study designed to assess both the presence and the sensitivity to ions and drugs of the K+ channels in the presynaptic nerve terminals of rat striatum. This method allowed differential measurement of the activity of two distinct components of 86Rb+ efflux, component V (sensitive to voltage and Ca2+-independent) and component C (Ca2+-activated). 2 A series of dopamine D-2 receptor agonists, including quinpirole, bromocriptine and Ru 24213, appeared to affect both components of 86Rb+ efflux. The EC50 values of quinpirole, bromocriptine and Ru 24213 for activating component V of 86Rb+ efflux were 5 pM, 15 pM and 40 pM, respectively. These drugs also stimulated component C of 86Rb+ efflux in the same order, but with lower, potency. 3 The dopaminergic D-2 agonist BHT 920 discriminated between the two components being active on component V (EC50 = 200 pM) and inactive on component C (up to 1 - μM). 4 Activation of voltage-sensitive 86Rb+ efflux by various dopamine D-2 receptor agonists, including BHT 920, were antagonized by 0.1 μM (-)-sulpiride but not by 0.1 μM yohimbine. 5 Lesioning of the nigro-striatal pathway by injection of 6-hydroxydopamine in the substantia nigra caused a reduction of about 60% of the BHT 920-stimulated, voltage-sensitive, Ca2+ independent 86Rb+ efflux (component V). 6 These data indicate that striatal presynaptic nerve terminals contain two distinct dopamine D-2 receptors which can be differentiated both functionally and pharmacologically.