Guanine nucleotide-binding protein G(o)-induced coupling of neuropeptide Y receptors to Ca2+ channels in sensory neurons

D. A. Ewald, P. C. Sternweis, R. J. Miller

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Neuropeptide Y (NPY) inhibited the Ca2+ current (I(Ca)) in rat dorsal root ganglion neurons in vitro. NPY inhibited the sustained I(Ca) evoked by steps to 0 mV from a holding potential of -40 mV and the inactivating I(Ca), which was additionally evoked from a more negative holding potential of -80 mV. The effects of NPY on both phases of the I(Ca) were abolished if cells were first treated with pertussis toxin (PTX). When a combination of GTP and the purified α-subunit of the guanine nucleotide-binding protein G(o) was perfused into PTX-treated cells, the inhibitory effects of NPY on the I(Ca) reappeared in a time-dependent fashion. GTP or α-subunit perfused separately was relatively ineffective. The effects of NPY reappeared more rapidly at higher concentrations of α(o). Chronic treatment of these cells with phorbol ester 'down-regulates' protein kinase C (PKC) and reduces inhibition of the sustained current by NPY. In PTX-treated cells in which PKC had been removed by down-regulation, inhibition of I(Ca) was also reconstituted following the perfusion of GTP/α(o). Under these circumstances, NPY inhibited the transient phase of the I(Ca) more than the sustained phase. These results indicate that G(o), the major PTX substrate in the central nervous system, may normally mediate the inhibitory effects of NPY receptors on dorsal root ganglion Ca2+ channels.

Original languageEnglish (US)
Pages (from-to)3633-3637
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - 1988

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