Dopamine receptor and adrenoceptor agonists inhibit prolactin release from MMQ cells.
MMQ cells, a prolactin-secreting cell line possessing dopamine receptors, were exposed to the calcium channel activator maitotoxin and dopamine or adrenoceptor agonists or antagonists. Dopamine (500 nM) or the dopamine agonists lisuride (50 nM), terguride (50 nM), and N-0437 (50 nM) decreased maitotoxin-stimulated prolactin release from perifused MMQ cells. In this system, sulpiride (100 nM), a dopamine D2 antagonist, reversed the prolactin inhibition produced by lisuride (20 nM). In static incubations of MMQ cells, lisuride (10-500 nM) inhibited maitotoxin-stimulated prolactin release in a concentration-dependent manner; this inhibition was attenuated in a concentration-related manner by sulpiride (100-500 nM). In addition, sulpiride reversed dopamine (50-500 nM), lisuride (10-500 nM), and terguride (50-500 nM) inhibition of forskolin-stimulated cAMP generation. The alpha 2-adrenergic agonist clonidine inhibited maitotoxin-stimulated prolactin release from perifused MMQ cells; this inhibition was abolished by idazoxan, an alpha 2-adrenergic antagonist. In contrast, serotonin or the serotonin antagonist methysergide had no effect on prolactin release from MMQ cells. These data indicate that activation of dopamine D2 receptors and alpha 2-adrenoceptors by classically defined pharmacological agents inhibits prolactin release and cellular cAMP levels in MMQ cells. Therefore, MMQ cells may provide a valuable model for the development of pharmacological agents and assist in the identification of the mechanisms involved in the dopaminergic inhibition of prolactin release.
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
A M
AM
Judd
R M
RM
MacLeod
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D004298:Dopamine / Q000494:pharmacology; D006801:Humans; D008090:Lisuride / Q000031:analogs & derivatives / Q000494:pharmacology; D008387:Marine Toxins / Q000037:antagonists & inhibitors; D035964:Oxocins; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology; D011388:Prolactin / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D000095702:Polyether Toxins
D000322:Adrenergic Agonists; D000242:Cyclic AMP; D004298:Dopamine; D008090:Lisuride; D008387:Marine Toxins; D035964:Oxocins; D011388:Prolactin; D011954:Receptors, Dopamine; C006208:dironyl; C020394:maitotoxin; D000095702:Polyether Toxins