抄録
Arachidonic acid (AA, 10 nM–2 μM), enhanced Ca2+-regulated exocytosis in acetylcholine (ACh) stimulated antral mucous cells of guinea pig. The AA actions were inhibited by MK886 (50 μM, an inhibitor of peroxisome proliferation activation receptor α (PPARα)), and were mimicked by PPARα agonists (Eicosatetraynoic acid (ETYA) and WY14643). The enhancement of ACh-stimulated exocytosis induced by AA, ETYA and WY14643 was eliminated by a PKG inhibitor (Rp8BrPET-cGMPS) and was mimicked by 8Br-cGMP. Nitro-L-arginine methyl ester (L-NAME) also inhibited the enhancement induced by AA, ETYA and WY14643, and NOC-12 (an NO donor) enhanced ACh-stimulated exocytosis similar to AA, ETYA and WY14643, which was inhibited by Rp8BrPET-cGMPS. ACh-stimulated exocytosis was partially inhibited by MK886, L-NAME and Rp8BrPET-cGMPS. AA, ETYA or WY14643 did not increase intracellular Ca2+ concentration ([Ca2+]i) and did not enhance an ACh-stimulated [Ca2+]i increase in antral mucous cells. Measurements of cGMP contents in antral mucosa demonstrated that stimulation with ACh, AA and PPARα agonists stimulate cGMP accumulation, which is inhibited by MK886 and L-NAME. In conclusion, in ACh-stimulated antral mucous cells, AA accumulated via phospholipase A2 stimulates PPARα, which activates the NO/cGMP cascade, and PKG activated by cGMP enhances Ca2+-regulated exocytosis in antral mucous cells. [J Physiol Sci. 2007;57 Suppl:S46]
