The permeant molecule urea stimulates prolactin secretion in GH4C1 cells by inducing Ca2+ influx through dihydropyridine-sensitive Ca2+ channels.
Isotonic urea in medium with a normal 1.2 mM Ca2+ concentration induced a striking rise in both cytosolic Ca2+ concentration ([Ca2+]i) and prolactin (PRL) secretion, each of whose peaks were proportional to the concentration of urea between 5 and 120 mM. There was a significant linear relationship between the peaks of induced [Ca2+]i and PRL secretion (r = 0.99, P less than 0.001). The increase in both [Ca2+]i and PRL secretion was completely abolished by removal of medium Ca2+ or by 2 microM nifedipine. Hypertonic urea was ineffective in inducing either an increase in [Ca2+]i or PRL secretion. These data support the hypothesis that plasma membrane expansion is a potent non-toxic inducer of hormone secretion and that in GH4C1 cells an increase in [Ca2+]i produced by enhanced influx of extracellular Ca2+ through dihydropyridine-sensitive Ca2+ channels plays an important role in this phenomenon.
Sato
N
N
Department of Medicine, Oregon Health Sciences University, Portland 97201.
Wang
X B
XB
Greer
M A
MA
Greer
S E
SE
McAdams
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D010911:Pituitary Neoplasms; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured; D014508:Urea / Q000494:pharmacology*
D015220:Calcium Channels; D014508:Urea; D011388:Prolactin; D009543:Nifedipine; D002118:Calcium