Medium hyperosmolarity depresses thyrotropin-releasing hormone-induced Ca2+ influx and prolactin secretion in GH4C1 cells.

We studied the influence of graded degrees of hyperosmolarity on the dynamics of the thyrotropin-releasing hormone (TRH)-induced rise in cytosol Ca2+ concentration (Ca2+]i) and prolactin (PRL) secretion in GH4C1 cells. TRH caused two phases of increase in Ca2+]i that were differentially altered by hyperosmolarity: 100% hyperosmolarity (600 mOsm) depressed only 20% of an initial high-amplitude Ca2+]i burst (first phase) dependent on Ca2+ mobilized from intracellular pools, but it abolished a sustained low-amplitude second phase dependent on extracellular Ca2+ influx. Low degrees of hyperosmolarity suppressed PRL secretion due to Ca2+ influx while high degrees suppressed secretion due to mobilized Ca2+. These data suggest that in GH4C1 cells hypertonic inhibition of secretion may result from both blocking Ca2+ influx and mechanisms unrelated to Ca2+]i.