Calmodulin- and protein phosphorylation-independent release of catecholamines from PC-12 cells

Heinrich J G Matthies; H. Clive Palfrey; Richard J. Miller

doi:10.1016/0014-5793(88)81132-3

Calmodulin- and protein phosphorylation-independent release of catecholamines from PC-12 cells

Heinrich J G Matthies, H. Clive Palfrey, Richard J. Miller^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Catecholamine secretion from PC-12 cells can be triggered by agents that increase intracellular Ca²⁺ and is enhanced by phorbol esters and agents that elevate intracellular cAMP concentrations. In mutant PC-12 cells lacking cAMP-dependent protein kinase (PK-A) in which protein kinase C (PK-C) was down-regulated, Ca²⁺-dependent secretion occurred normally but was no longer enhanced by cAMP or phorbol esters. In digitonin-permeabilized PC-12 cells that lacked PK-C and PK-A, a range of calmodulin (CaM) inhibitors failed to block Ca²⁺-triggered catecholamine release. Moreover, Mn²⁺, a CaM activator, failed to trigger catecholamine release whereas Ba²⁺, which does not activate CaM, supported secretion. These results indicate that the basic mechanism of stimulus/secretion coupling in PC-12 cells does not absolutely require a regulated protein phosphorylation- or calmodulin-dependent step.

Original language	English (US)
Pages (from-to)	238-242
Number of pages	5
Journal	FEBS Letters
Volume	229
Issue number	2
DOIs	https://doi.org/10.1016/0014-5793(88)81132-3
State	Published - Mar 14 1988

Keywords

(PC-12 cell)
Calmodulin
Exocytosis
Protein kinase C
cAMP-dependent protein kinase

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/0014-5793(88)81132-3

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title = "Calmodulin- and protein phosphorylation-independent release of catecholamines from PC-12 cells",

abstract = "Catecholamine secretion from PC-12 cells can be triggered by agents that increase intracellular Ca2+ and is enhanced by phorbol esters and agents that elevate intracellular cAMP concentrations. In mutant PC-12 cells lacking cAMP-dependent protein kinase (PK-A) in which protein kinase C (PK-C) was down-regulated, Ca2+-dependent secretion occurred normally but was no longer enhanced by cAMP or phorbol esters. In digitonin-permeabilized PC-12 cells that lacked PK-C and PK-A, a range of calmodulin (CaM) inhibitors failed to block Ca2+-triggered catecholamine release. Moreover, Mn2+, a CaM activator, failed to trigger catecholamine release whereas Ba2+, which does not activate CaM, supported secretion. These results indicate that the basic mechanism of stimulus/secretion coupling in PC-12 cells does not absolutely require a regulated protein phosphorylation- or calmodulin-dependent step.",

keywords = "(PC-12 cell), Calmodulin, Exocytosis, Protein kinase C, cAMP-dependent protein kinase",

author = "Matthies, {Heinrich J G} and Palfrey, {H. Clive} and Miller, {Richard J.}",

note = "Funding Information: AcknowledgementAs:1 26-lB2 cells were generouslys upplied by Dr J.A. Wagner.T his work was supportedb y grantsf rom the NIH to R.J.M. and H.C.P., and a predoctoralt raining grant to H.J.G.M. and by grantsf rom the Marion Labs and Miles, Inc. to R.J.M.",

year = "1988",

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doi = "10.1016/0014-5793(88)81132-3",

language = "English (US)",

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pages = "238--242",

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T1 - Calmodulin- and protein phosphorylation-independent release of catecholamines from PC-12 cells

AU - Matthies, Heinrich J G

AU - Palfrey, H. Clive

AU - Miller, Richard J.

N1 - Funding Information: AcknowledgementAs:1 26-lB2 cells were generouslys upplied by Dr J.A. Wagner.T his work was supportedb y grantsf rom the NIH to R.J.M. and H.C.P., and a predoctoralt raining grant to H.J.G.M. and by grantsf rom the Marion Labs and Miles, Inc. to R.J.M.

PY - 1988/3/14

Y1 - 1988/3/14

N2 - Catecholamine secretion from PC-12 cells can be triggered by agents that increase intracellular Ca2+ and is enhanced by phorbol esters and agents that elevate intracellular cAMP concentrations. In mutant PC-12 cells lacking cAMP-dependent protein kinase (PK-A) in which protein kinase C (PK-C) was down-regulated, Ca2+-dependent secretion occurred normally but was no longer enhanced by cAMP or phorbol esters. In digitonin-permeabilized PC-12 cells that lacked PK-C and PK-A, a range of calmodulin (CaM) inhibitors failed to block Ca2+-triggered catecholamine release. Moreover, Mn2+, a CaM activator, failed to trigger catecholamine release whereas Ba2+, which does not activate CaM, supported secretion. These results indicate that the basic mechanism of stimulus/secretion coupling in PC-12 cells does not absolutely require a regulated protein phosphorylation- or calmodulin-dependent step.

AB - Catecholamine secretion from PC-12 cells can be triggered by agents that increase intracellular Ca2+ and is enhanced by phorbol esters and agents that elevate intracellular cAMP concentrations. In mutant PC-12 cells lacking cAMP-dependent protein kinase (PK-A) in which protein kinase C (PK-C) was down-regulated, Ca2+-dependent secretion occurred normally but was no longer enhanced by cAMP or phorbol esters. In digitonin-permeabilized PC-12 cells that lacked PK-C and PK-A, a range of calmodulin (CaM) inhibitors failed to block Ca2+-triggered catecholamine release. Moreover, Mn2+, a CaM activator, failed to trigger catecholamine release whereas Ba2+, which does not activate CaM, supported secretion. These results indicate that the basic mechanism of stimulus/secretion coupling in PC-12 cells does not absolutely require a regulated protein phosphorylation- or calmodulin-dependent step.

KW - (PC-12 cell)

KW - Calmodulin

KW - Exocytosis

KW - Protein kinase C

KW - cAMP-dependent protein kinase

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Calmodulin- and protein phosphorylation-independent release of catecholamines from PC-12 cells

Abstract

Keywords

ASJC Scopus subject areas

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