Supraspinal inhibitory effects of chimeric peptide MCRT on gastrointestinal motility in mice

Abstract

(1) Morphiceptin and PFRTic-NH played important roles in the regulation of gastrointestinal motility; (2) MCRT possessed higher bioactivity of pain relief than gastrointestinal regulation, suggesting its promising analgesic property; (3) MCRT-induced motility disorders were sensitive to DOR but not to MOR blockade, indicating the pain-relieving specificity of speculated MOR subtype or splice variant or MOR-DOR heterodimer.

Cyclic derivatives of morphiceptin possess anti-transit effect in the gastrointestinal tract and alleviate abdominal pain in mice

“…The similar action was reported for MuDelta: at the doses range 10-25 mg/kg, po, it did not affect fecal pellet output in acclimated mice although in stressed mice MuDelta was effective already at the lowest dose tested (10 mg/kg, po) [22]. Chimeric peptide, MRCT, administered centrally significantly reduced fecal pellet output in mice (1.5-4 nmol/mouse, icv) in naloxone-reversible manner [18]. The results on mixed OR agonists and their influence on GI peristalsis are comparable: it appears that mixed OR agonists normalize accelerated GI peristalsis without constipating effect.…”

“…MCRT inhibited the emptying of the stomach and prolonged the transit along the small intestine in a dose-dependent manner (10-30 nmol/mouse, icv). This effect was reversed by non-selective OR antagonist, naloxone and selective DOP antagonist (naltrindole), but not cyprodime (MOP antagonist) [18].…”

“…Noteworthy, morphiceptin (0.3 and 1 mg/kg)-injected ip was inactive in the mouse GI tract [9]. However, when administered directly into the central nervous system (morphiceptin (10-30 nmol/mouse) significantly inhibited the transit along the small intestine [18].…”

“…However, this inhibitory action was observed in more detailed studies on the upper and lower parts of the GI tract only in case of compound 1 and P-317. Similarly, morphiceptin administered centrally (icv) significantly prolonged gastric emptying and inhibited upper GI transit in a dose-dependent manner (10-30 nmol/mouse) [18]. Moreover, He et al [18] evaluated the effect of MCRT (heptapeptide based on morphiceptin and a neuropeptide FF) at the upper GI transit.…”

“…Similarly, morphiceptin administered centrally (icv) significantly prolonged gastric emptying and inhibited upper GI transit in a dose-dependent manner (10-30 nmol/mouse) [18]. Moreover, He et al [18] evaluated the effect of MCRT (heptapeptide based on morphiceptin and a neuropeptide FF) at the upper GI transit. MCRT inhibited the emptying of the stomach and prolonged the transit along the small intestine in a dose-dependent manner (10-30 nmol/mouse, icv).…”