Involvement of cGMP-dependent protein kinase in adrenergic potentiation of transmitter release from the calyx-type presynaptic terminal

Hiromu Yawo

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    29 Citations (Scopus)

    Abstract

    I have previously reported that norepinephrine (NE) induces a sustained potentiation of transmitter release in the chick ciliary ganglion through a mechanism pharmacologically distinct from any known adrenergic receptors. Here I report that the adrenergic potentiation of transmitter release was enhanced by a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX) and by zaprinast, an inhibitor of cGMP-selective phosphodiesterase. Exogenous application of the membrane-permeable cGMP, 8-bromo-cGMP (8Br-cGMP), potentiated the quantal transmitter release, and after potentiation, the addition of NE was no longer effective. On the other hand, 8Br-cAMP neither potentiated the transmitter release nor occluded the NE-induced potentiation. The NE-induced potentiation was blocked by neither nitric oxide (NO) synthase inhibitor nor NO scavenger. The quantal transmitter release was not potentiated by NO donors, e.g., sodium nitroprusside. The NE-induced potentiation and its enhancement by IBMX was antagonized by two inhibitors of protein kinase G (PKG), Rp isomer of 8-(4-chlorophenylthio) guanosine-3',5'- cyclic monophosphorothioate and KT5823. As with NE-induced potentiation, the effects of 8Br-cGMP on both the resting intraterminal [Ca2+] ([Ca2+](i)) and the action potential-dependent increment of [Ca2+](i) (ΔCa) in the presynaptic terminal were negligible. The reduction of the paired pulse ratio of EPSC is consistent with the notion that the NE- and cGMP-dependent potentiation of transmitter release was attributable mainly to an increase of the exocytotic fusion probability. These results indicate that NE binds to a novel adrenergic receptor that activates guanylyl cyclase and that accumulation of cGMP activates PKG, which may phosphorylate a target protein involved in the exocytosis of synaptic vesicles.

    Original languageEnglish
    Pages (from-to)5293-5300
    Number of pages8
    JournalJournal of Neuroscience
    Volume19
    Issue number13
    DOIs
    Publication statusPublished - 1999 Jul 1

    Keywords

    • Adrenergic receptors
    • Neurotransmitter release
    • Presynaptic terminal
    • Protein kinase G
    • Synaptic plasticity
    • cGMP

    ASJC Scopus subject areas

    • Neuroscience(all)

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