Dopamine D2 receptor agonists are commonly used in the control of PRL-secreting adenomas, and the sensitivity of dopamine agonists during long term therapy is exquisite. However, the molecular mechanisms responsible for the maintenance of this cellular sensitivity to dopamine agonists remain poorly understood. In the present study, we examined the agonist-induced regulation of the human D2 L receptor expressed to a specific activity of ϳ1 pmol receptor/mg protein in Sf9 insect cells. Treatment

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... f D2 L receptor-expressing cells with dopamine for up to 3 h resulted in no detectable change in the ligandbinding properties of the receptor and a ϳ120-fold reduction in the potency, but not the efficacy, of D2 L receptors to mediate dopamine inhibition of forskolin-stimulated adenylyl cyclase activity. This resistance of the D2 L receptor to agonist-induced desensitization was accompanied by a ϳ28% translocation of intracellular D2 L receptors to the cell surface, as quantified by cellular fractionation and radioligand binding and visualized by whole cell immunocytochemical