Failure of dopamine and bromocriptine to affect prolactin release and cell growth in the dopamine receptor-deficient 235-1 clone.
The 235-1 clone was recently derived from the 7315a transplantable pituitary tumor and continues to secrete rat prolactin. The cells have a prominent Golgi apparatus which can be stained immunocytochemically for prolactin, but there were no 600-900 nm granules which are characteristic of normal mammotrophs. In a perfused cell-column apparatus, prolactin release from the clone was unchanged by dopaminergic agonists, thyrotropin-releasing hormone and estradiol but stimulated by dibutyryl cyclic AMP. Cellular cyclic AMP content was also not changed by dopamine but was dramatically enhanced by prostaglandin E1, indicating that at least one hormone-adenylate cyclase coupling mechanism was functional. In radioligand binding studies using the dopamine antagonist [3H]spiperone, no evidence of a dopamine receptor was obtained. The [3H]spiperone binding present was not stereoselective, and exceedingly high concentrations of other ligands were required to displace the binding. In addition, the induction of a prolactin-secreting hard tumor in rats by subcutaneous inoculation of the 235-1 cells failed to induce measurable dopamine receptors associated with the tumor cells. In order to address the possibility that there were functional dopamine receptors on these cells, but that they could not be resolved with either the cell column and cyclic AMP studies or the radioreceptor assay, the clone cells were incubated with 0.1-100 nM bromocriptine for up to 8 days. Bromocriptine had no effect on the growth rate or prolactin secretion of the 235-1 clone but inhibited prolactin release from anterior pituitary cells by over 73% in control studies. We conclude that the 235-1 clone does not express dopamine receptors and that the presence of dopamine receptors is obligatory for the typical inhibitory effects of bromocriptine on prolactin release and pituitary cell growth.
D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000378:metabolism / Q000648:ultrastructure; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011954:Receptors, Dopamine / Q000502:physiology*
D011954:Receptors, Dopamine; D001971:Bromocriptine; D011388:Prolactin; D004298:Dopamine