Effects of phospholipase A2 inhibitors on coupling of α2-adrenoceptors to inwardly rectifying potassium currents in guinea-pig submucosal neurones
Open Access
- 1 October 1993
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 110 (2), 591-596
- https://doi.org/10.1111/j.1476-5381.1993.tb13851.x
Abstract
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 μm) and 4-bromophenacyl bromide (4-BPB, 10 μm) 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 μm) and the lipoxygenase and cyclo-oxygenase inhibitor, eicosatetraynoic acid (ETYA, 20 μm) and nordihydroguairetic acid (NDGA, 20 μm) did not alter i.p.s.ps or hyperpolarizations to UK 14304. 4 Exogenously applied arachidonic acid (1–300 μm) 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.Keywords
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