Effects of phospholipase A2 inhibitors on coupling of alpha 2-adrenoceptors to inwardly rectifying potassium currents in guinea-pig submucosal neurones.
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 microM) and 4-bromophenacyl bromide (4-BPB, 10 microM) 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 microM) and the lipoxygenase and cyclo-oxygenase inhibitor, eicosatetraynoic acid (ETYA, 20 microM) and nordihydroguairetic acid (NDGA, 20 microM) did not alter i.p.s.ps or hyperpolarizations to UK 14304. 4. Exogenously applied arachidonic acid (1-300 microM) 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.
Evans
R J
RJ
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Surprenant
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000294:innervation / Q000378:metabolism*; D007478:Iontophoresis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D015221:Potassium Channels; D018341:Receptors, Adrenergic, alpha-2; D013004:Somatostatin; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D000109:Acetylcholine