THE ROLE OF ARACHIDONIC-ACID METABOLISM IN SOMATOSTATIN AND SUBSTANCE-P EFFECTS ON INWARD RECTIFIER K-CONDUCTANCE IN RAT-BRAIN NEURONS

Somatostatin enhances an inward rectifier K conductance in cultured lo cus coeruleus neurons, while substance P reduces an inward rectifier K conductance in cultured nucleus basalis and locus coeruleus neurons. The role of arachidonic acid metabolites in these responses was studie d. The somatostatin-induced response was reduced by phospholipase A2 i nhibitors, non-specific lipoxygenase inhibitors and specific 5-lipoxyg enase inhibitors. A cyclooxygenase inhibitor and a 12-lipoxygenase inh ibitor had no effect. 5(S)-HPETE occasionally increased the K conducta nce, but failed to occlude the somatostatin response. The substance P response was suppressed by a 5-lipoxygenase inhibitor but not by a 12- lipoxygenase inhibitor. These results suggest that the 5-lipoxygenase pathway is not a specific messenger of either one of these responses, but that it plays a more general role in maintaining or enhancing the effectiveness of both somatostatin and substance P responses.