Circular muscle contraction in the mice rectum plays a key role in morphine-induced constipation.

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (2014-07-22)
H Ono, A Nakamura, K Matsumoto, S Horie, G Sakaguchi, T Kanemasa
RESUMEN

Although opioids induce intestinal muscle contraction and provoke constipation, the intestinal region(s) that contribute to the constipation have remained unclear. We report here a region-specific response of intestinal muscle contraction to morphine and its correlation with in vivo constipation. Regions of mice small and large intestines were dissected histologically and circular muscle contractile responses were measured using isometric transducers. Bead expulsion assays were performed to assess in vivo constipation. The strongest contraction in response to morphine was detected in the rectum. The distal and transverse colon also showed strong contractions, whereas weak responses were detected in the proximal colon, jejunum, and ileum. Regarding the sustainability of muscle contractions during morphine exposure, prolonged waves were detected only in the rectum, while the waves diminished gradually in other regions. To identify the mechanism(s) underlying this difference, we focused on nitric oxide synthase (NOS). In the distal colon, decreased contraction during morphine exposure was recovered by application of a NOS inhibitor (L-NAME), while a NOS substrate (L-arginine) enhanced contractile degradation. In contrast L-NAME and L-arginine modestly affected the sustained contraction in the rectum. To confirm the correlation with constipation, beads were inserted into the transverse colon, distal colon, or rectum after morphine administration and expulsion times were examined. Beads tended to stop at the rectum even when inserted in the deeper colonic regions. The rectum showed the greatest response to morphine in both in vitro and in vivo analyses, therefore it may play a key role for opioid-induced constipation.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Sodium chloride, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
Sodium chloride, for molecular biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
Sodium chloride, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Sigma-Aldrich
Sodium chloride solution, 0.9% in water, BioXtra, suitable for cell culture
Sigma-Aldrich
L-Arginine, reagent grade, ≥98%
Sigma-Aldrich
Sodium chloride solution, 5 M in H2O, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
Calcium chloride solution, BioUltra, for molecular biology, ~1 M in H2O
Sigma-Aldrich
L-Arginine, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
Sodium chloride solution, 5 M
SAFC
Sodium chloride solution, 5 M
Sigma-Aldrich
Calcium chloride, meets USP testing specifications
Sigma-Aldrich
Calcium chloride, anhydrous, BioReagent, suitable for insect cell culture, suitable for plant cell culture, ≥96.0%
Sigma-Aldrich
Calcium chloride, anhydrous, powder, 99.99% trace metals basis
Sigma-Aldrich
Sodium chloride, meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%
SAFC
L-Arginine
Sigma-Aldrich
Sodium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
L-Arginine, 99%, FCC, FG
Supelco
Sodium chloride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Sodium chloride solution, 0.85%
Sigma-Aldrich
Sodium chloride solution, BioUltra, for molecular biology, ~5 M in H2O
Sigma-Aldrich
Sodium chloride, 99.999% trace metals basis
Supelco
Sodium chloride, certified reference material for titrimetry, certified by BAM, ≥99.5%
Supelco
L-Arginine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Calcium chloride, AnhydroBeads, −10 mesh, ≥99.9% trace metals basis
Sigma-Aldrich
Sodium chloride, BioPerformance Certified, ≥99% (titration), suitable for insect cell culture, suitable for plant cell culture
Sigma-Aldrich
Sodium chloride, tested according to Ph. Eur.
Sigma-Aldrich
L-Penicillamine, 99%
Supelco
Calcium ion solution for ISE, 0.1 M Ca, analytical standard (for ion-selective electrodes)
USP
Naloxone, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Sodium chloride, tablet