Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats

Effects of small bowel transplantation (SET) on ileal motility are unknown. The aim of the present study was to investigate changes in spontaneous contractile activity and sensitivity to cholinergic and adrenergic agents in the ileal circular muscle after SET in rats. Orthotopic SET was performed in syngeneic rats to avoid immune phenomena. Distal ileal circular muscle strips from rats one week (N = 10) and eight weeks (N = 10) after SET were stretched to optimal length (L-o), and basal spontaneous activity at L-o was measured. Dose-response experiments to the cholinergic agonist bethanechol (Be, 10(-8)-10(-4) M) were performed in the presence of tetrodotoxin (TTX, 10(-6) M) and to the adrenergic agonist norepinephrine (NE, 10(-8)-10(-4) M) with or without TTX. ED50 (negative log of drug-concentration that induced 50% effect) was calculated. We also studied rats with selective jejunoileal ischemia/reperfusion, intestinal transection/reanastomosis, naive controls, and sham operated controls (N greater than or equal to 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SET or in other groups compared to control tissue. After SET, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SET (5.1 +/- 0.3 vs 6.2 +/- 0.4 and 6.2 +/- 0.2, respectively; P < 0.05) regardless of the presence of TTX. No hypersensitivity was observed after ischemia-reperfusion, intestinal transection-reanastomosis, or sham operation. It is concluded that ileal hypersensitivity to NE was related to the extrinsic denervation obligated by the transplantation procedure, possibly mediated through an increase in number of receptors on smooth muscle, not on the enteric nerves.