モルモット胃幽門腺粘液細胞においてインドメサシンによるアラキドン酸蓄積が引き起こしたCa²⁺調節性開口放出の増強

抄録

Ca²⁺-regulated exocytosis is enhanced by the PGE₂/cAMP pathway in antral mucous cells of guinea pigs. The inhibition of the PGE₂/cAMP pathway by a PKA inhibitor (H-89) or aspirin (ASA) decreased the frequency of ACh-stimulated exocytotic events by 60%. Indomethacin (IDM), however, decreased the ACh-stimulated exocytotic events only by 30%. Moreover, IDM increased the ACh-stimulated exocytotic events by 50% in H-89-treated or ASA-treated cells. IDM inhibits the synthesis of PGG/H and 15R-HPETE, while ASA inhibits only PGG/H synthesis. Thus, IDM accumulates arachidonic acid (AA). AACOCF₃ or ACA (PLA₂ inhibitors), which inhibits AA synthesis, decreased the ACh-stimulated exocytotic events by 60%. IDM, however, did not increase the frequency in AACOCF₃-treated cells. AA increased the frequency of ACh-stimulated exocytotic events in AACOCF₃- or ASA-treated cells, similar to IDM in ASA-treated cells. Moreover, in the presence of AA, IDM did not further increase the ACh-stimulated exocytotic events in ASA-treated cells. The PGE₂ release from antral mucosa indicates that inhibition of PLA₂ by ACA decreases AA accumulation in unstimulated and ACh-stimulated antral mucosa. The dose-response study of AA and IDM demonstrated that the concentration of intracellular AA accumulated by IDM is less than 100 nM. In conclusion, IDM modulates ACh-stimulated exocytosis via AA accumulation in antral mucous cells. [J Physiol Sci. 2006;56 Suppl:S108]