Mechanisms of action of inhibitors of prolactin secretion in GH3 pituitary cells. I. Ca2+-dependent inhibition of amino acid incorporation.
Post-transcriptional protein synthesis by GH3 cloned pituitary cells, which secrete prolactin and growth hormone, is dependent on Ca2+. The effects of antagonists of prolactin secretion were examined on overall protein synthesis in GH3 cells as a function of cellular Ca2+ depletion and restoration at varying concentrations of extracellular Ca2+. Leucine incorporation by Ca2+-depleted cells during short incubations was reduced by 80-90%. Trifluoperazine at micromolar concentrations inhibited leucine incorporation in a Ca2+-dependent manner. The extent of inhibition varied with extracellular Ca2+ concentration and was fully reversed at higher Ca2+ concentrations. Similar patterns of inhibition of leucine incorporation were observed with nifedipine, verapamil, calmidazolium, chlorpromazine, bromocriptine, ergotamine, and the (+)- and (-)-isomers of butaclamol, but dopamine, apomorphine, and chlorpromazine sulfoxide were not inhibitory. Muscarinic agonists decreased incorporation in a Ca2+-dependent manner, but lesser degrees of inhibition were obtained. Inhibitions were observed for a broad spectrum of polypeptide species, could not be explained by effects on Mg2+ availability or amino acid uptake, and were rapidly and fully reversed by Ca2+. Production of prolactin and growth hormone was decreased by secretory inhibitors to the same extent and with the same Ca2+ concentration dependence as was observed for inhibition of amino acid incorporation. It is proposed that these substances inhibit protein synthesis in GH3 cells through alterations in intracellular Ca2+ metabolism rather than through mechanisms mediated by calmodulin or dopamine receptors.
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Brostrom
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D000109:Acetylcholine / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000596:Amino Acids; D007093:Imidazoles; D014268:Trifluoperazine; D001971:Bromocriptine; C031938:calmidazolium; D002217:Carbachol; D011388:Prolactin; D014700:Verapamil; D008274:Magnesium; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium; D002746:Chlorpromazine