Effects of phospholipase A₂ inhibitors on coupling of α₂‐adrenoceptors to inwardly rectifying potassium currents in guinea‐pig submucosal neurones

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 f4M) and 4-bromophenacyl bromide (4-BPB, 10 !LM) 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 tM) and the lipoxygenase and cyclo-oxygenase inhibitor, eicosatetraynoic acid (ETYA, 20 F.M) and nordihydroguairetic acid (NDGA, 201LM) did not alter i.p.s.ps or hyperpolarizations to UK 14304.4 Exogenously applied arachidonic acid (1-300 tM) 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.

α2‐Adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala: involvement of Gi/o‐protein‐mediated modulation of Ca2+‐channels and inwardly rectifying K+‐channels in LTD

“…Activation of the α 2 ‐adrenoreceptor can open K ir channels (Evans & Surprenant, 1993). Clonidine increased the membrane current elicited by a hyperpolarization ramp in the BLA in a voltage‐dependent manner, i.e.…”

Influence of some phospholipase A2and cytochrome P450 inhibitors on rat arterial smooth muscle K+currents

“…In neurones of the rat hippocampus (Mironov and Lux 1992), in ventricular myocytes of the rat (Stokke et al 1992) and guinea pig (Nagano et al 1996), and in smooth muscle cells from the guinea pig urinary bladder and vas deferens (Nagano et al 1996), an inhibitory influence of this substance on voltageactivated calcium channels has been shown. In addition, the inward rectifying K + conductance of guinea pig submucosal neurones (Evans and Surprenant 1993) and the endogenous glibenclamide-sensitive K + channel of Xenopus oocytes (Sakuta and Yoneda 1994) are inhibited by quinacrine.…”

Gastroprotective effect of Desmodium gangeticum roots on gastric ulcer mouse models

“…For acid secretion the expulsion of H + across the apical membrane is coupled with the movement of K + into the cell (Hanson & Hatt, 1989). Phospholipase A2 inhibitors are known to modulate proton conductance across cell membranes (Evans & Surprenant, 1993). Activation of parietal cell resulted in active transport of H + and associated with increased substrate oxidation may trigger the generation of H 2 O 2 like other cells.…”