Bromocriptine inhibits incorporation of [3H]thymidine into rat pituitary tumor cells.
The effects of bromocriptine on GH3 pituitary tumor cell [3H]thymidine incorporation were studied. Cells were grown in the presence of bromocriptine, then exposed to a short-term pulse of [3H]thymidine in serum-free medium containing deoxycytidine (10 microM) to prevent deoxythymidine triphosphate (dTTP) pooling. After 48 h exposure to bromocriptine, basal prolactin (PRL)-secretion during 45 min was inhibited by 50% by 10 microM bromocriptine and thyroid releasing hormone-induced PRL stimulation was suppressed. Incorporation of radiolabelled thymidine into acid-precipitable DNA increased progressively from 15 to 60 min and was abolished by simultaneous incubation with excess unlabelled thymidine (100 microM). Bromocriptine (10 microM) inhibited incorporation of 5-50 microM [3H]thymidine, but this was not reversed by simultaneous incubation with metoclopramide (10 microM). Aminopterin, an inhibitor of endogenous de novo DNA synthesis, stimulated [3H]thymidine incorporation twofold and this increased DNA salvage pathway activity was also blocked by bromocriptine. As incorporation of [3H]thymidine into acid-soluble cell nucleotides was also inhibited by bromocriptine, the data suggest that in these cells the drug inhibits thymidine kinase activity, a salvage pathway of DNA synthesis.
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Melmed
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Fagin
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Leung
D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology / Q000627:therapeutic use*; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism*; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors
D004273:DNA, Neoplasm; D011954:Receptors, Dopamine; D001971:Bromocriptine; D011388:Prolactin; D013937:Thymidine Kinase; D013936:Thymidine