Tetraethylammonium blockade of K+ channels in GH4C1 cells regulates prolactin secretion by inducing Ca2+ influx.
Tetraethylammonium (TEA), a K+ channel blocker, induced PRL secretion and an increase in cytosol Ca2+ concentration [Ca2+]i in a dose-dependent manner between 5-20 mM in GH4C1 rat pituitary tumor-derived cells. Removal of medium Ca2+ or the addition of 1 microM nifedipine abolished both the induced [Ca2+]i increment and PRL secretion. TEA augmented the TRH-induced rise in [Ca2+]i and inhibited the rise in [Ca2+]i induced by 30 mM K+. The dynamics of TEA-, TRH- and K(+)-induced PRL secretion were different, with the TEA-induced secretory peak occurring at about 10 min compared to 2-3 min for TRH and K+. Tolbutamide, which blocks ATP-sensitive K+ channels, induced PRL secretion without causing a rise in [Ca2+]i. The results suggest that: (a) K+ channels have a complex interaction with the PRL secretory process in GH4C1 cells; (b) TEA induces PRL secretion by causing Ca2+ influx through dihydropyridine-sensitive Ca2+ channels; and (c) K+ channels play a different role in the [Ca2+]i rise induced by TRH than in that induced by depolarizing K+.
Wang
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X
Department of Medicine, Oregon Health Sciences University, Portland.
Inukai
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T
Greer
M A
MA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D017136:Ion Transport / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D013973:Thyrotropin-Releasing Hormone; D019789:Tetraethylammonium; D011388:Prolactin; D014044:Tolbutamide; D009543:Nifedipine; D011188:Potassium; D002118:Calcium