Imidazoline NNC77-0074 stimulates Ca2+-evoked exocytosis in INS-1E cells by a phospholipase A2-dependent mechanism.
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Imidazoline NNC77-0074 stimulates Ca2+-evoked exocytosis in INS-1E cells by a phospholipase A2-dependent mechanism. / Olsen, Hervør L; Nørby, Peder L; Høy, Marianne; Spee, Pieter; Thams, Peter; Capito, Kirsten; Petersen, Jacob S; Gromada, Jesper.
In: Biochemical and Biophysical Research Communications, Vol. 303, No. 4, 2003, p. 1148-51.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Imidazoline NNC77-0074 stimulates Ca2+-evoked exocytosis in INS-1E cells by a phospholipase A2-dependent mechanism.
AU - Olsen, Hervør L
AU - Nørby, Peder L
AU - Høy, Marianne
AU - Spee, Pieter
AU - Thams, Peter
AU - Capito, Kirsten
AU - Petersen, Jacob S
AU - Gromada, Jesper
N1 - Keywords: Animals; Calcium Signaling; Cells, Cultured; Enzyme Inhibitors; Exocytosis; Group IV Phospholipases A2; Imidazoles; Islets of Langerhans; Male; Mice; Oligonucleotides, Antisense; Phospholipases A; Phospholipases A2; Pyridines; Tumor Cells, Cultured
PY - 2003
Y1 - 2003
N2 - We have previously demonstrated that the novel imidazoline compound (+)-2-(2-(4,5-dihydro-1H-imidazol-2-yl)-thiopene-2-yl-ethyl)-pyridine (NNC77-0074) increases insulin secretion from pancreatic beta-cells by stimulation of Ca(2+)-dependent exocytosis. Using capacitance measurements, we now show that NNC77-0074 stimulates exocytosis in clonal INS-1E cells. NNC77-0074-stimulated exocytosis was antagonised by the cytoplasmic phospholipase A(2) (cPLA(2)) inhibitors ACA and AACOCF(3) and in cells treated with antisense oligonucleotide against cPLA(2)alpha. NNC77-0074-evoked insulin secretion was likewise inhibited by ACA, AACOCF(3), and cPLA(2)alpha antisense oligonucleotide treatment. In pancreatic islets NNC77-0074 stimulated PLA(2) activity. We propose that cPLA(2)alpha plays an important role in the regulation of NNC77-0074-evoked exocytosis in insulin secreting beta-cells.
AB - We have previously demonstrated that the novel imidazoline compound (+)-2-(2-(4,5-dihydro-1H-imidazol-2-yl)-thiopene-2-yl-ethyl)-pyridine (NNC77-0074) increases insulin secretion from pancreatic beta-cells by stimulation of Ca(2+)-dependent exocytosis. Using capacitance measurements, we now show that NNC77-0074 stimulates exocytosis in clonal INS-1E cells. NNC77-0074-stimulated exocytosis was antagonised by the cytoplasmic phospholipase A(2) (cPLA(2)) inhibitors ACA and AACOCF(3) and in cells treated with antisense oligonucleotide against cPLA(2)alpha. NNC77-0074-evoked insulin secretion was likewise inhibited by ACA, AACOCF(3), and cPLA(2)alpha antisense oligonucleotide treatment. In pancreatic islets NNC77-0074 stimulated PLA(2) activity. We propose that cPLA(2)alpha plays an important role in the regulation of NNC77-0074-evoked exocytosis in insulin secreting beta-cells.
M3 - Journal article
C2 - 12684056
VL - 303
SP - 1148
EP - 1151
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -
ID: 8522104