Three phases of TRH-induced facilitation of exocytosis by single lactotrophs

Alla F Fomina, Edwin S. Levitan

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Membrane capacitance measurements were used to study neuropeptide modulation of exocytosis by perforated patch clamped rat lactotrophs. We report that depolarizing voltage-clamp pulses evoke exocytosis that is steeply dependent on Ca2+ influx through voltage-gated Ca2+ channels. Furthermore, we find that the neuropeptide TRH (thyrotropin-releasing hormone) acts in three phases to promote exocytosis. First, TRH transiently (within ~0.5 min) triggers depolarization- and extracellular Ca2+- independent exocytosis. Second, within 3 min of application, TRH facilitates depolarization-evoked exocytosis while inhibiting voltage-gated Ca2+ current. Finally, after 8 min, TRH further enhances depolarization-evoked exocytosis by increasing high-voltage-activated (HVA) Ca2+ channel current. Activation of protein kinase C (PKC) with a phorbol ester also stimulates depolarization-evoked exocytosis by increasing Ca2+ current. Therefore, PKC can only account for the last effect of TRH. Thus, a single neuromodulator may employ several temporally distinct mechanisms to stimulate peptide secretion.

Original languageEnglish (US)
Pages (from-to)4982-4991
Number of pages10
JournalJournal of Neuroscience
Volume15
Issue number7 I
StatePublished - Jul 1995
Externally publishedYes

Keywords

  • calcium channel
  • exocytosis
  • neuropeptide
  • pituitary
  • prolactin
  • protein kinase C

ASJC Scopus subject areas

  • Neuroscience(all)

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