EFFECTS OF PHOSPHOLIPASE-A(2) INHIBITORS ON COUPLING OF ALPHA(2)-ADRENOCEPTORS TO INWARDLY RECTIFYING POTASSIUM CURRENTS IN GUINEA-PIG SUBMUCOSAL NEURONS

1 Noradrenaline hyperpolarizes guinea-pig submucosal neurones by opening inwardly rectifying potassium channels. Intracellular recordings were made from submucosal neurones and the possible involvement of the phospholipase A2 pathway in this response was examined. 2 The non-specific phospholipase A2 inhibitors, quinacrine (10 muM) and 4-bromophenacyl bromide (4-BPB, 10 muM) inhibited nerve-evoked inhibitory synaptic potentials (i.p.s.ps) and hyperpolarizations to somatostatin and UK 14304. Quinacrine and 4-BPB also blocked the inward rectification present in current-voltage curves in the absence of somatostatin or UK 14304. 3 The more selective phospholipase A2 inhibitor, cyclosporin A (10 muM) and the lipoxygenase and cyclo-oxygenase inhibitor, eicosatetraynoic acid (ETYA, 20 muM) and nordihydroguairetic acid (NDGA, 20 muM) did not alter i.p.s.ps or hyperpolarizations to UK 14304. 4 Exogenously applied arachidonic acid (1-300 muM) did not mimic the i.p.s.p. or the hyperpolarization to UK 14304. 5 We conclude that arachidonic acid or its eicosanoid metabolites produced by phospholipase A2 stimulation are unlikely to be involved in the receptor G-protein coupled activation of potassium currents in submucosal neurones. The inhibition of the noradrenaline-induced hyperpolarization by quinacrine and 4-BPB is most likely due primarily to blockade of the basal inwardly rectifying potassium conductance present in these neurones.