Quinidine inhibits prolactin secretion induced by thyrotropin-releasing hormone, high medium potassium or hyposmolarity in GH4C1 cells.
In cultured GH4C1 cells quinidine inhibited basal prolactin (PRL) secretion and that induced by 0.1 to 10 nM thyrotropin-releasing hormone (TRH), 30 mM medium K+ or 30% medium hyposmolarity but did not inhibit secretion induced by 100 nM 12-O-tetradecanoylphorbol 13-acetate. Inhibition of basal PRL secretion was highly correlated with the drug concentration between 30 microM to 1 mM quinidine; 50% inhibition of basal secretion occurred at 300 microM and at this concentration quinidine completely blocked PRL secretion stimulated by TRH, K+ and hyposmolarity. Significant inhibition of TRH-induced PRL secretion was produced by 15 microM quinidine, a concentration equivalent to that in plasma during standard antiarrhythmic therapy with quinidine in humans. In rats in vivo, a single injection of 2 mg i.p. of quinidine gluconate/100 g b.wt. 1 hr before TRH injection significantly inhibited induced TSH secretion by 15%. Quinidine inhibition of secretion may be caused by blocking depolarization of the cell membrane, thus depressing voltage-gated Ca++ channels and preventing a rise in intracellular Ca++ release.
Wang
X B
XB
Department of Medicine, Oregon Health Sciences University, Portland.
Sato
N
N
Greer
M A
MA
Greer
S E
SE
McAdams
S
S
D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D009994:Osmolar Concentration; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D011188:Potassium / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism*; D011802:Quinidine / Q000493:pharmacokinetics / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000889:Anti-Arrhythmia Agents; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D013972:Thyrotropin; D011802:Quinidine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium