Opioid Receptors and Associated Regulator of G Protein Signaling Are Involved in the Cathartic Colon of Rats

A cathartic colon is characteristic of slow transit constipation (STC), which can result following the long-term use of irritant laxatives. In the present study, the involvement of three opioid receptor subtypes (μ, MOR; δ, DOR; and κ, KOR), regulator of G protein signaling 4 (RGS-4) and β-arrestin-2 were investigated in the cathartic colon of rats. A rat model of a cathartic colon was established by feeding the animals with phenolphthalein, while normal rats were used as a control. The mRNA and protein expression levels of the opioid receptors, RGS-4 and β-arrestin-2 were detected in the rat colon using semi-quantitative reverse transcription polymerase chain reaction and western blot analysis, respectively. The rat model of a cathartic colon was successfully established using the phenolphthalein stimulus, and was shown to result in shrunken myenteric neurons and loose muscle fibers in the intestinal wall. The mRNA and protein expression levels of the three opioid receptor subtypes, RGS-4 and β-arrestin-2 were significantly higher in the cathartic colon group when compared with the levels in the normal control group (all P<0.01). With regard to the protein expression levels, MOR protein increased 2.4 fold, DOR expression increased 1.5 fold, KOR levels increased 1.5 fold, RGS-4 protein increased 3.5 fold and β-arrestin-2 expression increased 2.0 fold. Therefore, the expression levels of opioid receptors were found to increase in the cathartic colons of the rats, indicating that opioid receptors and downstream RGS-4 and β-arrestin-2 signaling may play an important role in the pathogenesis of STC.