التفاصيل البيبلوغرافية
| العنوان: |
CPLA[sub 2α]-evoked formation of arachidonic acid and lysophospholipids is required for exocytosis in mouse pancreatic β-cells. |
| المؤلفون: |
Juhl, Kirstine, Høy, Marianne, Olsen, Hervør L., Bokvist, Krister, Efanov, Alexander M., Hoffmann, Else K., Gromada, Jesper |
| المصدر: |
American Journal of Physiology: Endocrinology & Metabolism; Jul2003, Vol. 48 Issue 1, pE73, 9p, 9 Graphs |
| مصطلحات موضوعية: |
ARACHIDONIC acid, PHOSPHOLIPIDS, EXOCYTOSIS, PANCREATIC beta cells |
| مستخلص: |
Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A[sub 2] (cPLA[sub 2]α) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca[sup 2+]-dependent exocytosis in single mouse pancreatic β-cells, cPLA[sub 2]α dose dependently (EC[sub 50] = 86 nM) stimulated depolarization-evoked exocytosis by 450% without affecting the whole cell Ca[sup 2+] current or cytoplasmic Ca[sup 2+] levels. The stimulatory effect involved priming of secretory granules as reflected by an increase in the size of the readily releasable pool of granules from 70-80 to 280-300. cPLA[sub 2]αstimulated exocytosis was antagonized by the specific cPLA[sub 2] inhibitor AACOCF[sub 3]. Ca[sup 2+]-evoked exocytosis was reduced by 40% in cells treated with AACOCF[sub 3] or an antisense oligonucleotide against cPLA[sub 2]α. The action of cPLA[sub 2]α was mimicked by a combination of arachidonic acid and lysophosphatidylcholine (470% stimulation) in which each compound alone doubled the exocytotic response. Priming of insulin-containing secretory granules has been reported to involve Cl[sup -] uptake through ClC-3 Cl[sup -] channels. Accordingly, the stimulatory action of cPLA[sub 2]α was inhibited by the Cl[sup -] channel inhibitor DIDS and in cells pretreated with ClC-3 Cl[sup -] channel antisense oligonucleotides. We propose that cPLA[sub 2]α has an important role in controlling the rate of exocytosis in β-cells. This effect of cPLA[sub 2]α reflects an enhanced transgranular Cl[sup -] flux, leading to an increase in the number of granules available for release, and requires the combined actions of arachidonic acid and lysophosphatidylcholine. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
