Hydrogen peroxide reduces beta-adrenoceptor function in the rat small intestine

Abstract

Incubation of isolated rat intestinal segments with hydrogen peroxide (H2O2) led to a decreased beta-adrenoceptor response. The maximal relaxation induced by isoprenaline was lowered while the EC50 remained unaffected. The effect of H2O2 in the small intestine increased slightly from duodenum to ileum. In the ileum, 10(-4) M H2O2 led to a 10% decrease of the maximal relaxation due to isoprenaline and 1 mM decreased the maximal response to about 50%. We further investigated the level at which the isoprenaline response was impaired. The relaxation caused by the stable cAMP analog, dibutyryl-cAMP, or by the adenylate cyclase activator, forskolin, was not affected or affected less than by isoprenaline. When the response to isoprenaline was expressed relative to the maximal response to dibutyryl-cAMP or forskolin, pretreatment with H2O2 led to a decreased isoprenaline response relative to the response to dibutyryl-cAMP or forskolin. This might indicate that exposure to H2O2 leads to a disturbance in receptor-mediated cAMP production. The adenylate cyclase unit is probably not affected since the response to forskolin is relatively resistant to H2O2. Our conclusion is that pretreatment of isolated intestinal segments with H2O2 leads to disturbed beta-adrenoceptor coupling, probably due to altered membrane integrity.