Effect of thienorphine on intestinal transit and isolated guinea-pig ileum contraction

Abstract

Aim: To evaluate the effect of thienorphine on small intestinal transit in vivo and on guinea-pig ileum (GPI) contraction in vitro.

Methods: The effects of thienorphine on intestinal transit were examined in mice and in isolated GPI. Buprenorphine and morphine served as controls. The distance traveled by the head of the charchol and the total length of the intestine were measured in vivo. Gastrointestinal transit was expressed as a percentage of the distance traveled by the head of the marker relative to the total length of the small intestine. The isolated GPI preparations were connected to an isotonic force transducer and equilibrated for at least 1 h before exposure to drugs. Acetylcholine was used for muscle stimulation.

Results: Thienorphine (0.005-1.0 mg/kg, ig) or buprenorphine (0.005-1.0 mg/kg, sc) dose-dependently significantly inhibited gut transit compared with saline. Thienorphine inhibited gut transit less than buprenorphine. The maximum inhibition by thienorphine on the intestinal transit was 50%-60%, whereas the maximum inhibition by morphine on gut transit was about 100%. Thienorphine also exhibited less inhibition on acetylcholine-induced contraction of GPI, with a maximum inhibition of 65%, compared with 93% inhibition by buprenorphine and 100% inhibition by morphine. Thienorphine induced a concentration-dependent decrease in the basal tonus of spontaneous movement of the GPI, the effect of which was weaker than that with buprenorphine. The duration of the effect of thienorphine on the GPI was longer than that with buprenorphine.

Conclusion: Thienorphine had less influence, but a longer duration of action on GPI contraction and moderately inhibited intestinal transit.

Keywords: Buprenorphine; Contraction; Guinea-pig ileum; Gut transit; Thienorphine.

Figure 1

Chemical structure of thienorphine and buprenorphine.

Figure 2

Effects of thienorphine, buprenorphine, morphine and naloxone on gastrointestinal propulsive activity in Kunming mice. Gastrointestinal transit was expressed as % of the distance traveled by an orally administered marker relative to the total length of the small intestine over 15 min after marker administration. Each column and vertical bar represent the mean ± SE of 9-10 mice. Thie: Thienorphine; Bup: Buprenorphine; Mor: Morphine; NLX: Naloxone.

Figure 3

Effects of naloxone on the gastrointestinal propulsive activity in Kunming mice treated with thienorphine (0.5 mg/kg), buprenorphine (0.5 mg/kg), or morphine (10 mg/kg). Gastrointestinal transit was expressed as % of the distance traveled by an orally administered marker relative to the total length of the small intestine over 15 min after marker administration. Each column and vertical bar represent the mean ± SE of 9-10 mice. ^aP < 0.05, ^bP < 0.001 vs intestinal transit without naloxone treatment. Thie: Thienorphine; Bup: Buprenorphine; Mor: Morphine.

Figure 4

Typical trace of thienorphine, buprenorphine, naloxone and morphine on guinea-pig ileum. A: Spontaneous movement of the guinea-pig ileum without chemical; B: The basal tonus decreased after buprenorphine (10.0 μmol/L) treatment; C: The basal tonus decreased after thienorphine (10.0 μmol/L) treatment; D: Spontaneous movement increased after naloxone (0.5 mmol/L) treatment; E: The basal tonus and spontaneous movement increased after morphine (1.6 mmol/L) treatment. The arrow indicates the addition of chemicals. Con: Control; Thie: Thienorphine; Bup: Buprenorphine; Mor: Morphine; NLX: Naloxone.

Figure 5

Effects of thienorphine, buprenorphine and morphine on the basal tonus of spontaneous movement of the guinea-pig ileum. Each point represents the mean ± SE (n = 5 or 6 preparations). A: Thienorphine (Thie) or buprenorphine (Bup) concentration-dependently decreased the basal tonus of guinea-pig ileum (GPI); B: Morphine (Mor) concentration-dependently increased the basal tonus of GPI; C: Naloxone (NLX, 0.50 mmol/L), Thie (32.0 μmol/L) or Bup (32.0 μmol/L) antagonized the elevation of basal tonus of GPI induced by Mor (2.4 mmol/L). ^aP < 0.05, ^bP < 0.001 vs the basal tonus before chemical application.

Figure 6

Effects of thienorphine, buprenorphine, morphine and naloxone on Ach-induced guinea-pig ileum contraction. Values represent mean ± SE for 4-6 preparations. Thie: Thienorphine; Bup: Buprenorphine; Mor: Morphine; NLX: Naloxone.

Figure 7

Time course of the amplitude inhibited by thienorphine (100 μmol/L), buprenorphine (100 μmol/L), morphine (3.2 mmol/L) or naloxone (1.0 mmol/L) on guinea-pig ileum contraction induced by Ach (1 μmol/L) during the prolonged washing process. The data are expressed as % amplitude with respect to the amplitude before chemical application, and each point represents the mean ± SE (n = 4). Thie: Thienorphine; Bup: Buprenorphine; Mor: Morphine; NLX: Naloxone.