Role of extracellular calcium and calmodulin in prolactin secretion induced by hyposmolarity, thyrotropin-releasing hormone, and high K+ in GH4C1 cells.
The mechanism by which 30% medium hyposmolarity induces PRL secretion by GH4C1 cells was compared with that induced by 100 nmol/l TRH or 30 mmol/l K+. Removing medium Ca2+, blocking Ca2+ channels with 50 mumol/l verapamil, or inhibiting calmodulin activation with 20 mumol/l trifluoperazine, 10 mumol/l chlorpromazine or 10 mumol/l pimozide almost completely blocked hyposmolarity-induced secretion. The smooth muscle relaxant, W-7, which is believed relatively specific in inhibiting the Ca2(+)-calmodulin interaction, depressed hyposmolarity-induced PRL secretion in a dose-dependent manner (r = -0.991, p less than 0.01). The above drugs also blocked or decreased high K(+)-induced secretion, but had much less effect on TRH-induced secretion. Secretion induced by TRH, hyposmolarity, or high K+ was optimal at pH 7.3-7.65 and was significantly depressed at pH 6.0 or 8.0, indicating that release of hormone induced by all 3 stimuli is due to an active cell process requiring a physiologic extracellular pH and is not produced by nonspecific cell toxicity. The data suggest hyposmolarity and high K+ may share some similarities in their mechanism of stimulating secretion, which is different from that of TRH.
Wang
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XB
Department of Medicine, Oregon Health Sciences University, Portland.
Sato
N
N
Greer
M A
MA
Greer
S E
SE
McAdams
S
S
D000818:Animals; D002118:Calcium / Q000172:deficiency / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D003470:Culture Media; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002147:Calmodulin; D003470:Culture Media; D013449:Sulfonamides; D013973:Thyrotropin-Releasing Hormone; C017967:W 7; D011388:Prolactin; D014700:Verapamil; D011188:Potassium; D002118:Calcium