Rapid stimulation of Ins(1,4,5)P3 production in rat aorta by NE: Correlation with contractile state

V. Pijuan, I. Sukholutskaya, W. Glenn Kerrick, M. Lam, C. Van Breemen, I. Litosch

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Abstract

The isomeric composition of inositol phosphates generated in response to norepinephrine (NE) stimulation and the relationship of inositol phosphate production to release of intracellular Ca2+ as measured by contraction were characterized in rat aorta prelabeled with [3H]inositol. NE stimulated a rapid and transient increase in labeled D-myo-inositol 1,4,5-trisphosphate [Ins-(1,4,5)P3] levels. A maximal increase in labeled Ins(1,4,5)P3 occurred within 15 s of stimulation followed by a decline to control levels at 5 min. D-Myo-inositol 1,3,4-trisphosphate [Ins-(1,3,4)P3] and D-myo-inositol 1- monophosphate [Ins(1)P] levels also increased rapidly in response to NE. In contrast to the transient production of Ins(1,4,5)P3, Ins(1,3,4)P3 and Ins(1)P production was maintained in the presence of NE. Half-maximal stimulation of Ins(1,4,5)P3 production and Ca2+ release occurred at 0.3 μM NE, and maximal effects were obtained with 10 μM NE. The concentration- response curve and time course for production of Ins(1,4,5)P3 correlated with the neurotransmitter-induced Ca2+ release from intracellular stores, indicating that the level of Ins(1,4,5)P3 regulated the Ca2+-release mechanism. In the continued presence of NE, the intracellular pools did not completely refill with Ca2+ despite the return of Ins-(1,4,5)P3 levels to basal at 5 min. These results demonstrate that NE stimulates a rapid increase in Ins(1,4,5)P3 that correlates with contraction in Ca2+-free buffer. The reuptake of Ca2+ into intracellular stores is regulated by a mechanism that may not involve Ins(1,4,5)P3.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number1 33-1
StatePublished - Jan 1 1993

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Keywords

  • calcium ion mobilization
  • inositol phosphates
  • norepinephrine
  • vascular smooth muscle

ASJC Scopus subject areas

  • Physiology

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