Free intracellular Ca2+ concentration ([Ca2+]i) and growth hormone release from purified rat somatotrophs. II. Somatostatin lowers [Ca2+]i by inhibiting Ca2+ influx.

This study was carried out to investigate the role of Ca2+ in the somatostatin (SRIF)-induced inhibition of GH release. We examined the effect of SRIF on basal and GH-releasing factor (GRF)-induced increases in Ca2+ influx and free intracellular Ca2+ concentration ([Ca2+]i) in normal somatotrophs and examined the effect of SRIF on 45Ca uptake, [Ca2+]i measured with indo-1, and GH release. SRIF inhibited basal and GRF-induced GH release concurrently with a reduction in steady state 45Ca uptake. In nonsteady state experiments, SRIF also decreased basal 45Ca uptake. SRIF decreased baseline [Ca2+]i in a concentration-dependent manner and inhibited the GRF-induced biphasic increase in [Ca2+]i, but in a differential fashion. Low concentrations of SRIF abolished the peak (first phase) without affecting the plateau (second phase), while at high concentrations, both phases were inhibited. SRIF blocked the GRF-induced increase in [Ca2+]i regardless of whether it was applied before or during GRF stimulation. These data indicate that the SRIF-dependent decrease in 45Ca uptake is due to a decrease in Ca2+ influx. This is further supported by the fact that the GRF-dependent increase in [Ca2+]i, which is dependent on Ca2+ influx, is blocked by SRIF. The reported ability of SRIF to reduce the activation rate of Ca2+ currents, decrease Ca2+ conductance, and hyperpolarize the cell would explain the differential effect of SRIF on the GRF-induced [Ca2+]i increase. The inhibitory effect of SRIF on GH release would then be dependent on the ability of SRIF to decrease, or prevent, an increase in [Ca2+]i.