Medium hyposmolarity stimulates prolactin secretion in GH4C1 cells by inducing an increase in cytosolic free calcium.
Extracellular hyposmolarity is a potent direct stimulus for hormone secretion for which a mechanism has not been delineated. The importance of plasmalemma Ca2+ permeability in this phenomenon in pituitary tumor-derived GH4C1 cells was evaluated by comparing the dynamics of changes in cytosolic free Ca2+ concentration [( Ca2+]i) with those of PRL secretion. At a normal physiological concentration of extracellular Ca2+ (1.5 mM), hyposmolarity induced a striking rise in both [Ca2+]i and PRL secretion, which was proportional to the stimulus between 0.50% reduction in medium osmolarity. Thirty percent hyposmolarity induced a 3-fold rise in [Ca2+]i and a 5-fold rise in PRL secretion above the basal level. These effects did not occur in cells incubated in a medium with a Ca2+ concentration lower than 30 microM. In cells incubated in 1.5 mM Ca2+, the Ca2(+)-channel antagonists, nifedipine and verapamil, significantly inhibited hyposmolar-induced increases in [Ca2+]i and PRL secretion. These data suggest that in GH4C1 cells medium hyposmolarity causes a burst of PRL secretion that depends on a similar preceding rise in [Ca2+]i produced by extracellular Ca2+ influx, most of which passes through dihydropyridine-sensitive Ca2(+)-channels.
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
Oshima
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003470:Culture Media; D003600:Cytosol / Q000378:metabolism; D007038:Hypotonic Solutions; D007700:Kinetics; D009543:Nifedipine / Q000494:pharmacology; D010911:Pituitary Neoplasms; D011388:Prolactin / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D003470:Culture Media; D007038:Hypotonic Solutions; D011388:Prolactin; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium