Mechanisms mediating somatostatin-induced reduction of cytosolic free calcium in PC12 cells.

In PC12 cells, somatostatin (SRIF) decreases the Ca2+ influx in response to high K+ through the inhibition of voltage-dependent Ca2+ channels. In the present study, we measured the intracellular Ca2+ concentration ( [Ca2+]i) following the application of SRIF-14 or its analogues which bind to different SRIF subtype (sst) receptors. Their application differentially reduces [Ca2+]i (octreotide > SRIF-14 > CGP23996 > BIM23056) in a dose-dependent manner. Pretreatment with a SRIF antagonist prevents the SRIF-induced inhibition of [Ca2+]i. These results suggest the involvement of specific membrane receptors and are in line with recent findings indicating the presence of receptor mRNAs on PC12 cells. Our results also exclude the possibility that SRIF interacts with opioid receptors and suggest that the SRIF-induced inhibition of [Ca2+]i is mediated by mechanisms involving PTX-sensitive G-proteins and PK-dependent pathways.