In single, superfused, FURA-2AM loaded insulin producing HIT-TIS cells, gastrin releasing peptide (GRP) induced a peak in cytoplasmic Ca2+ ([Ca2+](i)) followed by a sustained (high GRP concentrations) or oscillatory (low GRP concentrations) [Ca2+](i) pattern. The GRP (25-50 pM)-induced [Ca2+](i) oscillations ceased upon removal of glucose or addition of thapsigargin (1 mu M), EGTA (2 mM), or diazoxide (200 mu M), whereas nifedipine (10 mu M) reduced their amplitude (by 35%). Both protein kinase C (PKC)-activation or PKC-inhibition disrupted GRP induced [Ca2+](i) oscillations. GRP induced [Ca2+](i) oscillations in insulin producing cells therefore rely on intracellular Ca2+ mobilization, voltage-dependent and voltage-independent Ca2+ entry mechanisms and the integrity of protein kinase C. (C) 1999 Elsevier Science inc. All rights reserved.