PARADOXICAL EFFECTS OF DOPAMINE (DA) - G(I-ALPHA-3) MEDIATES DA INHIBITION OF PRL RELEASE WHILE MASKING ITS PRL-RELEASING ACTIVITY

In an attempt to elucidate the mechanism(s) underlying the paradoxical (inhibitory vs. stimulatory) effects of DA on PRL release, we treated permeabilized pituitary cells with antibodies directed against the ca rboxyl-terminus of the alpha-subunit of the guanine nucleotide binding protein, G(i3) Immunoneutralization of G(i alpha 3) completely blocke d the inhibitory effect of 1000 nM DA on PRL release, as assessed by r everse hemolytic plaque assays. In contrast, DA at a 100-fold lower co ncentration (10 nM) had no effect on PRL release under control conditi ons, but elicited a stimulatory response in the presence of anti-G(i a lpha 3). Examination of the frequency distribution of plaque sizes ind icated that suppression and augmentation of PRL secretion by DA was no t attributable to distinct subpopulations of lactotropes. Taken togeth er, these data suggest that all pituitary lactotropes have the potenti al to respond to the inhibitory and stimulatory activities of DA. Howe ver, the stimulatory action of this monoamine is normally masked by to nic activation of G(i alpha 3) which couples DA to its inhibitory path way.