Journal of Neuroscience, Vol 15, 4982-4991, Copyright © 1995 by Society for Neuroscience
Three phases of TRH-induced facilitation of exocytosis by single lactotrophs
AF Fomina and ES Levitan
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261, USA.
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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