Scientific article

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

Published inThe Journal of biological chemistry, vol. 267, no. 7, p. 4349-4356
Publication date1992

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

  • Arginine Vasopressin/ pharmacology
  • Calcium Channels/drug effects
  • Cations, Divalent
  • Cell Line/drug effects
  • Chromatography, Ion Exchange
  • Diazoxide/pharmacology
  • Diglycerides/biosynthesis
  • Inositol 1,4,5-Trisphosphate/metabolism
  • Inositol Phosphates/ metabolism
  • Insulin/ secretion
  • Isomerism
  • Membrane Potentials
  • Nickel/pharmacology
  • Nifedipine/pharmacology
  • Phosphorylation
Citation (ISO format)
LI, Guodong et al. Inositol tetrakisphosphate isomers and elevation of cytosolic Ca2+ in vasopressin-stimulated insulin-secreting RINm5F cells. In: The Journal of biological chemistry, 1992, vol. 267, n° 7, p. 4349–4356. doi: 10.1016/S0021-9258(18)42842-6
Main files (1)
ISSN of the journal0021-9258

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