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

AF Fomina and ES Levitan
Journal of Neuroscience 1 July 1995, 15 (7) 4982-4991; DOI: https://doi.org/10.1523/JNEUROSCI.15-07-04982.1995
AF Fomina
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261, USA.
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ES Levitan
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261, USA.
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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 approximately 0.5 min) triggers depolarization- and extracellular Ca(2+)-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.

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The Journal of Neuroscience: 15 (7)
Journal of Neuroscience
Vol. 15, Issue 7
1 Jul 1995
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Three phases of TRH-induced facilitation of exocytosis by single lactotrophs
AF Fomina, ES Levitan
Journal of Neuroscience 1 July 1995, 15 (7) 4982-4991; DOI: 10.1523/JNEUROSCI.15-07-04982.1995

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Three phases of TRH-induced facilitation of exocytosis by single lactotrophs
AF Fomina, ES Levitan
Journal of Neuroscience 1 July 1995, 15 (7) 4982-4991; DOI: 10.1523/JNEUROSCI.15-07-04982.1995
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