Dissociation between exocytosis and Ca2+-channel activity in mouse pancreatic β-cells stimulated with calmidazolium (compound R24571)

Henrik Kindmark; Martin Köhler; Olof Larsson; Akhtar Khan; Per Olof Berggren

doi:10.1016/0014-5793(95)00774-4

Dissociation between exocytosis and Ca²⁺-channel activity in mouse pancreatic β-cells stimulated with calmidazolium (compound R24571)

Henrik Kindmark, Martin Köhler, Olof Larsson, Akhtar Khan, Per Olof Berggren

Surgery

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

9 Scopus citations

Abstract

Calmidazolium, a calmodulin inhibitor, suppressed influx of Ca²⁺ through voltage-gated Ca²⁺ channels in mouse pancreatic β-cells. Despite this fact, calmidazolium stimulated insulin release from β-cells at basal glucose concentration. This effect was not mediated by protein kinase C (PKC), since it persisted in PKC-depleted cells. R_pcAMPS significantly attenuated tha calmidazolium-stimulated insulin secretion, indicating that calmidazolium acts, at least partly, through PKA. The compound also stimulated insulin secretion from electropermeabilized β-cells, indicating effects on distal steps in the stimulus-secretion coupling. The use of calmidazolium offers possibilities to investigate the mechanisms activating exocytosis under conditions where the cytoplasmic-free Ca²⁺ concentration does not increase.

Original language	English (US)
Pages (from-to)	315-320
Number of pages	6
Journal	FEBS letters
Volume	369
Issue number	2-3
DOIs	https://doi.org/10.1016/0014-5793(95)00774-4
State	Published - Aug 7 1995

Keywords

Calmidazolium
Insulin secretion
Protein kinase A
Voltage-gated Ca channel

ASJC Scopus subject areas

Biochemistry
Biophysics
Cell Biology
Genetics
Molecular Biology
Structural Biology

Access to Document

10.1016/0014-5793(95)00774-4

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title = "Dissociation between exocytosis and Ca2+-channel activity in mouse pancreatic β-cells stimulated with calmidazolium (compound R24571)",

abstract = "Calmidazolium, a calmodulin inhibitor, suppressed influx of Ca2+ through voltage-gated Ca2+ channels in mouse pancreatic β-cells. Despite this fact, calmidazolium stimulated insulin release from β-cells at basal glucose concentration. This effect was not mediated by protein kinase C (PKC), since it persisted in PKC-depleted cells. RpcAMPS significantly attenuated tha calmidazolium-stimulated insulin secretion, indicating that calmidazolium acts, at least partly, through PKA. The compound also stimulated insulin secretion from electropermeabilized β-cells, indicating effects on distal steps in the stimulus-secretion coupling. The use of calmidazolium offers possibilities to investigate the mechanisms activating exocytosis under conditions where the cytoplasmic-free Ca2+ concentration does not increase.",

keywords = "Calmidazolium, Insulin secretion, Protein kinase A, Voltage-gated Ca channel",

author = "Henrik Kindmark and Martin K{\"o}hler and Olof Larsson and Akhtar Khan and Berggren, {Per Olof}",

note = "Funding Information: A cknowledgements: We thank Yvonne Str6mberg and Tsegga Zeccarias for expert technical assistance with the radioimmunological measurements o1{"} insulin. Financial support was obtained from the Swedish Medical Research Council (03X-09890, 19x-00034, (14X-0989t), the Juvenile Diabetes Foundation International, the Swedish Diabetes Association, the Nordic Insulin Foundation, Magnus Bergvalls Foundation. Lars Hiertas Memorial Foundation, NOVO Industry, Funds of the Karolinska Institute, Clas Groschinskys Memorial Foundation, the Swedish Society of Medicine and F6renade \[,iv Mutual Group Life Insurance Company.",

year = "1995",

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doi = "10.1016/0014-5793(95)00774-4",

language = "English (US)",

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T1 - Dissociation between exocytosis and Ca2+-channel activity in mouse pancreatic β-cells stimulated with calmidazolium (compound R24571)

AU - Kindmark, Henrik

AU - Köhler, Martin

AU - Larsson, Olof

AU - Khan, Akhtar

AU - Berggren, Per Olof

N1 - Funding Information: A cknowledgements: We thank Yvonne Str6mberg and Tsegga Zeccarias for expert technical assistance with the radioimmunological measurements o1" insulin. Financial support was obtained from the Swedish Medical Research Council (03X-09890, 19x-00034, (14X-0989t), the Juvenile Diabetes Foundation International, the Swedish Diabetes Association, the Nordic Insulin Foundation, Magnus Bergvalls Foundation. Lars Hiertas Memorial Foundation, NOVO Industry, Funds of the Karolinska Institute, Clas Groschinskys Memorial Foundation, the Swedish Society of Medicine and F6renade \[,iv Mutual Group Life Insurance Company.

PY - 1995/8/7

Y1 - 1995/8/7

N2 - Calmidazolium, a calmodulin inhibitor, suppressed influx of Ca2+ through voltage-gated Ca2+ channels in mouse pancreatic β-cells. Despite this fact, calmidazolium stimulated insulin release from β-cells at basal glucose concentration. This effect was not mediated by protein kinase C (PKC), since it persisted in PKC-depleted cells. RpcAMPS significantly attenuated tha calmidazolium-stimulated insulin secretion, indicating that calmidazolium acts, at least partly, through PKA. The compound also stimulated insulin secretion from electropermeabilized β-cells, indicating effects on distal steps in the stimulus-secretion coupling. The use of calmidazolium offers possibilities to investigate the mechanisms activating exocytosis under conditions where the cytoplasmic-free Ca2+ concentration does not increase.

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