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PMID: 10662827 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Ca(2+)-evoked serotonin secretion by parafollicular cells: roles in signal transduction of phosphatidylinositol 3'-kinase, and the gamma and zeta isoforms of protein kinase C.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 4 ·2000-02-15 ·Pages 1365-73

Liu K, Hsiung S, Adlersberg M, Sacktor T, Gershon MD, Tamir H

Abstract

Parafollicular (PF) cells secrete 5-HT in response to stimulation of a G-protein-coupled Ca(2+) receptor (CaR) by increased extracellular Ca(2+) (upward arrow[Ca(2+)](e)). We tested the hypothesis that protein kinase C (PKC) participates in stimulus-secretion coupling. Immunoblots from membrane and cytosolic fractions of isolated PF cells revealed conventional (alpha, betaI, and gamma), novel (delta and epsilon), and atypical (iota/lambda and zeta) PKCs. Only PKCgamma was found to have been translocated to the membrane fraction when secretion of 5-HT was evoked by upward arrow[Ca(2+)](e) or phorbol esters. Although phorbol downregulation caused PKCgamma to disappear, secretion was only partially inhibited. A similar reduction of upward arrow[Ca(2+)](e)-evoked secretion was produced by inhibitors of conventional and/or novel PKCs (Gö 6976, calphostin C, and pseudoA), and these compounds did not inhibit secretion at all when applied to phorbol-downregulated cells. In contrast, the phorbol downregulation-resistant component of secretion was abolished by pseudoZ, which inhibits the atypical PKCzeta. Stimulation of PF cells with upward arrow[Ca(2+)](e) increased the activity of immunoprecipitated PKCzeta (but not PKCiota/lambda), and the activity of this PKCzeta was inhibited by pseudoZ. PF cells were found to express regulatory (p85) and catalytic (p110alpha and p110beta) subunits of phosphatidylinositol 3'-kinase (PI3'-kinase). upward arrow[Ca(2+)](e) increased the activity of immunoprecipitated PI3'-kinase; moreover, PI3'-kinase inhibitors (wortmannin and LY294002) antagonized secretion. We suggest that PKC isoforms mediate secretion of 5-HT by PF cells in response to stimulation of the CaR. PKC involvement can be accounted for by PKCgamma and an isoform sensitive to inhibition by pseudoZ, probably PKCzeta, which is activated via PI3'-kinase.

MeSH Terms
Androstadienes/pharmacology Animals Calcium/physiology Calcium Channels/drug effects,physiology Carbazoles/pharmacology Cell Membrane/enzymology Cells, Cultured Cytosol/enzymology Enzyme Inhibitors/pharmacology Indoles/pharmacology Isoenzymes/metabolism Naphthalenes/pharmacology Phosphatidylinositol 3-Kinases/metabolism Protein Kinase C/metabolism Serotonin/metabolism Sheep Signal Transduction/physiology Tetradecanoylphorbol Acetate/pharmacology Thyroid Gland/cytology,drug effects,physiology Wortmannin
Chemicals
Androstadienes Calcium Channels Carbazoles Enzyme Inhibitors Indoles Isoenzymes Naphthalenes Go 6976 Serotonin Phosphatidylinositol 3-Kinases protein kinase C gamma protein kinase C zeta Protein Kinase C calphostin C Tetradecanoylphorbol Acetate Calcium Wortmannin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Liu K
Division of Neuroscience, New York State Psychiatric Institute, New York, New York 10032, USA.
Hsiung S
Adlersberg M
Sacktor T
Gershon M D
Tamir H
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
2000-02-15
Pages
1365-73
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772377
Subset
IM
Grants
NINDS NIH HHS · NS12969 · United States
NIMH NIH HHS · R29 MH053576 · United States
NIDDK NIH HHS · DK52139 · United States
NIMH NIH HHS · 5 P30 R29MH53576 · United States
NINDS NIH HHS · R01 NS012969 · United States
NCI NIH HHS · P30 CA013696 · United States
NIMH NIH HHS · R01 MH057068 · United States
External Links
PubMed source PMC Full Text View journal details
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