The lipid peroxidation product 4-hydroxy-2,3-trans-1 nonenal decreases rat intestinal smooth muscle function in-vitro by alkylation of sulphydryl groups

Abstract

The effects of the lipid peroxidation product 4-hydroxy-2,3-trans-1 nonenal (HNE) on intestinal smooth muscle function have been studied. Exposure of rat isolated small intestinal segments to HNE (0.1-0.5 mM) led to decreased muscarinic and beta-adrenergic responses. The maximal response to the muscarinic agonist methacholine and its pEC50 decreased in a dose dependent manner. The response to the beta-adrenoceptor agonist isoprenaline was affected in a similar manner, but at slightly higher concentrations of HNE. As HNE has been described to be sulphydryl-reactive these effects were compared with the effects of the sulphydryl-reactive agent N-ethylmaleimide (NEM). Incubation of intestinal segments with NEM had similar effects on pharmacological responses to methacholine, indicating that the effects of HNE like that of NEM are likely to be caused by alkylation of sulphydryl groups. Dithiothreitol, a compound which reduces oxidized sulphydryl groups, was unable to restore the effects of HNE or NEM, which suggests that the effects of HNE and NEM are irreversible.