Opiate-induced constipation related to activation of small intestine opioid μ2-receptors

AIM： To investigate the role of opioid p-receptor subtype in opiate-induced constipation （OIC）.METHODS： The effect of Ioperamide on intestinal transit was investigated in mice. Ileum strips were isolated from 12-wk-old male BALB/c mice for identification of isometric tension. The ileum strips were precontracted with 1 μmol/L acetylcholine （ACh）. Then, decrease in muscle tone （relaxation） was characterized after cumu- lative administration of 0.1-10μ~mol/L Ioperamide into the organ bath, for a concentration-dependent study. Specific blockers or antagonists were used for pretreat- ment to compare the changes in Ioperamide-induced relaxation.RESULTS： In addition to the delay in intestinal transit, Ioperamide produced a marked relaxation in isolated ileum precontracted with ACh, in a dose-dependent manner. This relaxation was abolished by cyprodime,a selective opioid p-receptor antagonist, but not modified by naloxonazine at a dose sufficient to block opioid μ-1 receptors. Also, treatment with opioid μ-1 receptor agonist failed to modify the muscle tone. Moreover, the relaxation by Ioperamide was attenuated by glibenclamide at a dose sufficient to block ATP-sensitive K^＋ （KATP） channels, and by protein kinase A （PKA） inhibitor, but was enhanced by an inhibitor of phosphodiesterase for cyclic adenosine monophosphate （cAMP）.CONCLUSION： Loperamide induces intestinal relaxa- tion by activation of opioid μ-2 receptors via the cAMP- PKA pathway to open KATp channels, relates to OIC.

Myofiber Permeability and Force Production of Rat Muscles Following Eccentric Contractions: The Repeated Bout Effect Depends on the Interval

Past eccentric contraction (ECC)-induced muscle injury reduces the severity of symptoms of subsequent muscle injury;this phenomenon is known as a repeated bout effect (RBE). It has been reported that increases in the duration of the interval between the first and second bouts are linked to weakening of the RBE. However, the histology following the attenuation of the RBE remains unclear. We examined the sustained effects of the second bout with regard to myofiber permeability and muscle force. Sixty-four male rats were randomly assigned to eight groups that varied in the number of exercise sessions and the duration of the interval between the first and second bouts: the non-ECC (Control);the single-injury (Post 1st bout);groups that were allowed to recover for 1, 2, and 4 weeks after a single injury (Pre 2nd bout_1w, Pre 2nd bout_2w, and Pre 2nd bout_4w);and groups that were subjected to second injuries 1, 2, and 4 weeks after the first (Post 2nd bout_1w, Post 2nd bout_2w, and Post 2nd bout_4w). The tibialis anterior was electrically stimulated in each ECC group. Twenty-four hours before muscle sampling, Evans blue dye (EBD) (a marker of myofiber damage) was administered. The maximal isometric contraction tension was measured immediately before sampling. The number of EBD-positive (+) fibers was determined via histological analysis. An RBE was revealed by functional examination at the 1- and 2-week and histological examination at the 1-, 2-, and 4-week time points (P < 0.05). In terms of myofiber permeability, prolongation of the interval before the second bout weakened this effect (P < 0.05). Experiments with 1-, 2-, and 4-week intervals indicated that prolongation of the interval before the second bout weakened the RBE with regard to myofiber permeability.