Inhibitory effects of arachidonic acid on muscarinic current response in single pancreatic acinar cells of rats.

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RESUMO

1. In single, enzymatically dissociated rat pancreatic acinar cells both acetylcholine (ACh) stimulation and IP3 (inositol 1,4,5-trisphosphate) injection evoke Ca2(+)-dependent transient responses. Exogenously applied arachidonic acid (AA) inhibits both responses in a dose-dependent manner. 2. Arachidonic acid oxidation inhibitors, indomethacin and nordihydroguaiaretic acid, cause no significant changes in ACh- and IP3-induced responses. The inhibitory effects of AA (50 microM) on IP3-induced responses are not influenced by the presence of these oxidation inhibitors. 3. An inhibitor of phospholipase A2 (PLA2), 4-bromophenacyl bromide (4-BPB; 10 microM), augments the ACh-induced response, and it potentiates the IP3-induced response by a factor of 10 to 20. The IP3-induced response, after its complete decay, is recovered by an administration of 4-BPB. 4. The results suggest that an increase in [Ca2+]i, induced by IP3 injection, activates PLA2, and that this resultant release of AA in turn inhibits IP3-dependent Ca2+ mobilization.

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