Phorbol Ester Pretreatment Desensitizes the Inhibition of Ca2+ Channels Induced by k‐Opiate, α2‐Adrenergic, and Muscarinic Receptor Agonists

Bernard Attali, Seung‐Yeol ‐Y Nah, Zvi Vogel

Research output: Contribution to journalArticlepeer-review

Abstract

: Acute treatment of rat spinal cord‐dorsal root ganglion cocultured neurons with 12‐O‐tetradecanoylphorbol 13‐acetate (TPA), a known activator of protein kinase C, inhibited the dihydropyridinc‐sensitive voltage‐dependent 45Ca2+ influx measured in these cells (IC50 of⋍100 nM, 66% inhibition at 1 νM TPA). However, prolonged preincubation (24 h) of the cells with 100 nM TPA followed by extensive washing completely abolished, i.e., desensitized, the capacity of a second application of TPA to inhibit the activity of the voltage‐dependent Ca2+ channels. Moreover, this treatment also abolished the inhibition of Ca2+ influx produced by k‐opiate as well as by α2‐adrenergic and muscarinic receptor agonists. Substantial desensitization was already observed following a 1‐h pretreatment with 100 nMTPA. In contrast to TPA, an inactive phorbol ester (4β‐phorbol 13‐acetate) did not affect the inhibition of the voltage‐dependent Ca2+ influx by these receptor agonists. These results suggest that protein kinase C may have a role in the modulation of Ca2+channels by k‐opiate, α2‐adrenetgic, and muscarinic receptor agonists.

Original languageEnglish
Pages (from-to)1803-1806
Number of pages4
JournalJournal of Neurochemistry
Volume57
Issue number5
DOIs
StatePublished - Nov 1991
Externally publishedYes

Keywords

  • Ca channels
  • Phorbol ester
  • Protein kinase C
  • Receptor desensitization
  • k opiate

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