Enhancement of Ca2+-regulated exocytosis by indomethacin in guinea-pig antral mucous cells: arachidonic acid accumulation.

Autor: Fujiwara, Shoko, Shimamoto, Chikao, Nakanishi, Yoshihiko, Katsu, Ken-ichi, Kato, Masumi, Nakahari, Takashi
Předmět:
Zdroj: Experimental Physiology; Jan2006, Vol. 91 Issue 1, p249-259, 11p, 1 Diagram, 9 Graphs
Abstrakt: Ca2+-regulated exocytosis is enhanced by an autocrine mechanism via the PGE2–cAMP pathway in antral mucous cells of guinea-pigs. The inhibition of the PGE2–cAMP pathway by H-89 (an inhibitor of protein kinase A, PKA) or aspirin (ASA, an inhibitor of cyclo-oxygenase, COX) decreased the frequency of ACh-stimulated exocytotic events by 60%. Indomethacin (IDM, an inhibitor of COX), however, decreased the frequency of ACh-stimulated exocytotic events only by 30%. Moreover, IDM increased the frequency of ACh-stimulated exocytotic events by 50% in H-89-treated or ASA-treated cells. IDM inhibits the synthesis of Prostaglandin (PGG/H) and (15R)-15-hydroxy-5,8,11 cis-13-trans-eicosatetraenoic acid (15R-HPETE), while ASA inhibits only the synthesis of PGG/H. Thus, IDM may accumulate arachidonic acid (AA). AACOCF3 or N-( p-amylcinnamoyl) anthranilic acid (ACA; both inhibitors of phospholipase A2, PLA2), which inhibits AA synthesis, decreased the frequency of 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- and H-89-treated cells. Moreover, in the presence of AA, IDM did not increase the frequency of ACh-stimulated exocytotic events in ASA-treated cells. The PGE2 release from antral mucosa indicates that inhibition of PLA2 by ACA inhibits the 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 the ACh-stimulated exocytosis via AA accumulation in antral mucous cells. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index