Adenosine 3',5'-cyclic monophosphate-mediated prolactin secretion in GH4C1 cells involves Ca2+ influx through L-type Ca2+ channels.
In normal anterior pituitary cells adenosine 3',5'-cyclic monophosphate (cAMP)-mediated prolactin (PRL) secretion requires Ca2+ influx. However, the role of Ca2+ in cAMP-induced secretion in the clonal rat pituitary tumor-derived GH4C1 cells remains uncertain. We examined in GH4C1 cells the effects of forskolin (FSK), an adenylate cyclase activator, and dibutyryl cAMP (DB-cAMP) on PRL secretion and intracellular Ca2+ ([Ca2+]i) dynamics. Ca2+ depletion of the medium inhibited FSK and DB-cAMP stimulated PRL secretion approximately 50%. Both FSK and DB-cAMP increased [Ca2+]i in a dose-dependent fashion. The peak amplitude in [Ca2+]i in response to each concentration of these stimuli was achieved in 3 min, corresponding to the peak PRL response to the same stimuli. Either Ca2+ depletion of the medium or addition of 2 microM nifedipine (NF) abolished the increase in [Ca2+]i caused by FSK or DB-cAMP. Our data indicate that an increase in intracellular c-AMP in GH4C1 cells produces an elevation of [Ca2+]i by opening L-type Ca2+ channels and that c-AMP-mediated PRL secretion is augmented by Ca2+ influx in GH4C1 cells as in normal pituitary cells.
Department of Medicine, Oregon Health Sciences University, Portland.
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Inukai
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Wang
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Greer
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Greer
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010911:Pituitary Neoplasms; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D005576:Colforsin; D003994:Bucladesine; D011388:Prolactin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D009543:Nifedipine; D002118:Calcium