Inositol tetrakisphosphate isomers and elevation of cytosolic Ca2+ in vasopressin-stimulated insulin-secreting RINm5F cells.

摘要: Signal generation during the stimulation of insulin secretion by arginine vasopressin (AVP) was investigated in RINm5F cells. AVP (0.1 microM) caused a biphasic cytosolic Ca2+ ([Ca2+]i) rise, namely rapid transient marked elevation after followed series oscillations. In absence extracellular Ca2+, sustained oscillations were abolished, while initial [Ca2+]i only partly decreased, indicating that former are due to influx and latter mainly mobilization from internal stores. also evoked depolarization average membrane potential. AVP-induced phase, which strictly dependent on receptor occupancy, attenuated hyperpolarization with diazoxide. However, blockade channels L- or T-type ineffective. stimulated production diacylglycerol inositol phosphates; for both [3H] labeling mass determinations performed. A increase Ins(1,4,5)P3 enhancement Ins(1,3,4,5)P4 (8-fold) peaking at 15 s gradually returning basal values. Ins(1,3,4,6)P4 Ins(3,4,5,6)P4 exhibited most long-lasting augmentation (4- 1.7-fold, respectively), therefore correlated best period InsP5 InsP6 not elevated. The effects AVP, including perifused cells, obliterated V1 antagonist. conclusion, induces protracted cells is associated increases InsP4 isomers. accumulation isomers reflects occupancy accelerated metabolism phosphates. Activation second messenger-operated necessarily implicated because attenuating effect hyperpolarization.