The intrinsic activity of (-)-3-PPP vis-à-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 D2 receptor agonist (-)-(3-hydroxyphenyl)-N-n-propylpiperidine, (-)-3-PPP, to suppress prolactin (PRL) release induced by any of five different PRL secretagogues in GH4C1 cells transfected with the human D2 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 D2 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 D2 agonist with respect to D2-mediated suppression of PRL release may vary from agonism to antagonism depending on which intracellular transduction systems that are being concomitantly activated.
Nilsson
C L
CL
Department of Pharmacology, Institute of Physiology and Pharmacology, Göteborg University, Sweden. neuroendo@pharm.gu.se
Hellstrand
M
M
Ekman
A
A
Eriksson
E
E
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D002460:Cell Line; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D006801:Humans; D010880:Piperidines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D018491:Dopamine Agonists; D010880:Piperidines; D017448:Receptors, Dopamine D2; D014660:Vasoactive Intestinal Peptide; D013973:Thyrotropin-Releasing Hormone; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011388:Prolactin; C026539:preclamol; D011188:Potassium; D004298:Dopamine