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 language | English (US) |
|---|---|
| Pages (from-to) | 4982-4991 |
| Number of pages | 10 |
| Journal | Journal of Neuroscience |
| Volume | 15 |
| Issue number | 7 I |
| State | Published - Jul 1995 |
| Externally published | Yes |
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Keywords
- calcium channel
- exocytosis
- neuropeptide
- pituitary
- prolactin
- protein kinase C
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Three phases of TRH-induced facilitation of exocytosis by single lactotrophs. / Fomina, Alla F; Levitan, Edwin S.
In: Journal of Neuroscience, Vol. 15, No. 7 I, 07.1995, p. 4982-4991.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Three phases of TRH-induced facilitation of exocytosis by single lactotrophs
AU - Fomina, Alla F
AU - Levitan, Edwin S.
PY - 1995/7
Y1 - 1995/7
N2 - 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.
AB - 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.
KW - calcium channel
KW - exocytosis
KW - neuropeptide
KW - pituitary
KW - prolactin
KW - protein kinase C
UR - http://www.scopus.com/inward/record.url?scp=0029016670&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029016670&partnerID=8YFLogxK
M3 - Article
C2 - 7623127
AN - SCOPUS:0029016670
VL - 15
SP - 4982
EP - 4991
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 7 I
ER -