Functional Selectivity of Dopamine Receptor Agonists. II. Actions of Dihydrexidine in D2L Receptor-Transfected MN9D Cells

D2-like dopamine receptors mediate functional changes via activation of inhibitory G proteins, including those that affect adenylate cyclase activity, and potassium and calcium chan-nels. Although it is assumed that the binding of a drug to a single isoform of a D2-like receptor will cause similar changes in all receptor-mediated functions, it has been demonstrated in brain that the dopamine agonists dihydrexidine (DHX) and N-n-propyl-DHX are “functionally selective”. The current study ex-plores the underlying mechanism using transfected MN9D cells and D2-producing anterior pituitary lactotrophs. Both dopamine and DHX inhibited adenylate cyclase activity in a concentration-dependent manner in both systems, effects blocked by D2, but not D1, antagonists. In the MN9D cells, quinpirole and R-()-N-propylnorapomorphine (NPA) also inhibited the K-stimu