Medium hyperosmolarity inhibits prolactin secretion induced by depolarizing K+ in GH4C1 cells by blocking Ca2+ influx

Medium hyperosmolarity between 300 (normal medium osmolarity) and 600 mOsm inhibited in a concentration-correlated fashion (r greater than 0.97, p less than 0.001) the rise in intracellular Ca2+ concentration ([Ca2+]i) and prolactin (PRL) secretion induced in GH4C1 cells by depolarizing 30 mM K+. [Ca2+]i concentration and PRL secretion were tightly related between 300 and 600 mOsm (r = 0.976, p less than 0.001); 50% inhibition of both occurred at 450 mOsm. Medium hyperosmolarity slowed the rate of Ca2+ influx. At 600 mOsm the rise in both [Ca2+]i and PRL secretion was abolished but PRL secretion induced by 1 microM phorbol 12-myristate 13-acetate was not significantly reduced. Our data suggest that inhibition of Ca2+ influx may be the primary mechanism by which extracellular hyperosmolarity inhibits PRL secretion induced by high medium K+ in GH4C1 cells. Depression of the Ca2+ intracellular transduction system may play a pathophysiological role in vivo in conditions such as dehydration and hypertonic coma.