Influence of Chronic Depolarization on Synthesis and the Relative Amounts of Different Forms of Somatostatin in Cultured Fetal Cerebrocortical Cells

The neuropeptide somatostatin is widely distributed throughout the nervous system. In addition to its well known role as a hypophysiotropic hormone, somatostatin also appears to serve as a neurotransmitter or neuromodulator (1,2). Although the effects of conventional neural depolarizing agents on the release of somatostatin (SRIF) have been extensively studied (3), little is known about the influence of these agents on SRIF synthesis and processing. We and others previously reported that in using cultured fetal cerebral cortical cells, immunoreactive (ir)-SRIF release occurred in response to acute depolarization induced by high potassium concentrations or veratridine (VTD) (3,4). In the present work, we sought to investigate to what extent SRIF synthesis is regulated by factors that influence its secretion, by studying the effect of chronic exposure to depolarizing agents on ir-SRIF synthesized by cultured cortical cells. As an index of synthesis, we followed the accumulation of ir-SRIF (cell content + media). We examined the response of the cultured neurons to high concentrations of K+ and found that K+ increased total ir-SRIF and that this effect is calcium-dependent.