Imidazoline NNC77-0074 stimulates Ca2+-evoked exocytosis in INS-1E cells by a phospholipase A2-dependent mechanism.
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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.
Original language | English |
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Journal | Biochemical and Biophysical Research Communications |
Volume | 303 |
Issue number | 4 |
Pages (from-to) | 1148-51 |
Number of pages | 3 |
ISSN | 0006-291X |
Publication status | Published - 2003 |
Bibliographical note
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
ID: 8522104