Inhibition of adrenal medullary catecholamine secretion by enflurane: II. Investigations in isolated bovine adrenals--site and mechanism of action.

To determine the site and mechanism of action underlying the inhibition of adrenal medullary catecholamine release by enflurane, the authors measured the effects of enflurane on catecholamine secretion evoked by various secretagogues in isolated bovine adrenals perfused with Locke's solution. Catecholamine concentrations in the perfusate were measured spectrofluorometrically. Enflurane caused concentration-dependent inhibition of catecholamine release in response to activation of the nicotinic receptors in the chromaffin cells with acetylcholine or dimethylphenylpiperazinium (DMPP). An enflurane concentration of 0.88 mM caused 50 per cent inhibition of the DMPP-induced secretion. The inhibition induced by enflurane was shown to be noncompetitive. The catecholamine release evoked by activation of the muscarinic receptors with pilocarpine was only slightly decreased by 3.74 mM enflurane. At this concentration the release in response to KCl, 56 mM, was partially inhibited, whereas the output in response to tyramine (from glands perfused with calcium-free Locke's solution) was unaffected. It is concluded that the site of action of enflurane is the cell membrane. At concentrations above 1 mM, enflurane may impair calcium ion influx, but at lower concentrations it probably interacts with hydrophobic regions of the nicotinic receptor.