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

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.