Inhibition of Prolactin Release from Anterior Pituitary Lactotrophs in Culture by Sulfur-Containing Analogs of Dopamine

Abstract The effects of permanently charged and uncharged analogs of dopamine were examined for their ability to inhibit basal prolactin release from primary cultures of rat pituitary lactotrophs. The charged quaternary trimethyldopamine and the charged dimethylsulfonium analogs were active (IC50's were 4.3 and 31 μM, respectively) while the permanently uncharged monoethylsulfide was devoid of significant activity. Dopamine and dimethyldopamine, which are able to exist in both charged and uncharged forms, are more potent (IC50's were 36 and 44 nM, respectively) but all compounds were capable of approaching the same maximum degree of prolactin release inhibition. Haloperidol, a dopamine receptor antagonist, was able to block the actions of each of the agonists. The data suggest that (a) dopamine agonists do not have to be in the uncharged form in order to activate the dopamine receptor that regulates prolactin release, (b) the uncharged monomethylsulfide analog of dopamine is incapable of activating the dopamine receptor, and (c) the nitrogen on the side chain of dopamine can be replaced by another atom and still retain prolactin release inhibiting activity.