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Phorbol Ester Pretreatment Desensitizes the Inhibition of Ca 2+ Channels Induced by k ‐Opiate, α 2 ‐Adrenergic, and Muscarinic Receptor Agonists
Author(s) -
Attali Bernard,
Nah SeungYeol,
Vogel Zvi
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb06384.x
Subject(s) - protein kinase c , muscarinic acetylcholine receptor , endocrinology , chemistry , medicine , phorbol , activator (genetics) , receptor , depolarization , biophysics , biochemistry , biology , kinase
: 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 45 Ca 2+ influx measured in these cells (IC 50 of⋍100 n M , 66% inhibition at 1 ν M TPA). However, prolonged preincubation (24 h) of the cells with 100 n M 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 Ca 2+ channels. Moreover, this treatment also abolished the inhibition of Ca 2+ influx produced by k ‐opiate as well as by α 2 ‐adrenergic and muscarinic receptor agonists. Substantial desensitization was already observed following a 1‐h pretreatment with 100 n M TPA. In contrast to TPA, an inactive phorbol ester (4β‐phorbol 13‐acetate) did not affect the inhibition of the voltage‐dependent Ca 2+ influx by these receptor agonists. These results suggest that protein kinase C may have a role in the modulation of Ca 2+ channels by k ‐opiate, α 2 ‐adrenetgic, and muscarinic receptor agonists.