The intrinsic activity of (-)-3-PPP vis-a-vis prolactin-suppressing dopamine D2 receptors in transfected GH4C1 cells is dependent on which secretagogue that is used to provoke prolactin release

The abilities of dopamine (DA) and the partial DA D-2 receptor agonist (-)-(3-hydroxyphenyl)-N-n-propylpiperidine, (-)-3-PPP, to suppress prolactin (PRL) release induced by any of five different PRL secretagogues in GH(4)C(1) cells transfected with the human D-2 receptor (short isoform) were investigated. Whereas DA reduced the response to all five secretagogues, (-)-3-PPP reduced the response to vasoactive intestinal peptide (VIP) and thyrotropin-releasing hormone (TRH), but not to high medium potassium (K+) or to the potassium channel antagonist tetraethylammonium (TEA). (-)-3-PPP tended to reduce the PRL release induced by the Ca2+ channel agonist BAY K-8644 (BAY); however, this effect of the partial agonist was modest and not significant. Whereas the effects of both DA and (-)-3-PPP on the PRL response to VIP and TRH were counteracted by co-incubation with the D-2 antagonist raclopride, the effects of DA on the PRL response to K+, BAY, and TEA were antagonized by co-incubation with either raclopride or(-)-3-PPP. The results show that, at a given receptor density, the intrinsic activity of a partial D-2 agonist with respect to D-2-mediated suppression of PRL release may vary from agonism to antagonism depending on which intracellular transduction systems that are being concomitantly activated. (C) 1998 Elsevier Science Ltd. All rights reserved.