Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats.
Effects of small bowel transplantation (SBT) 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 SBT in rats. Orthotopic SBT 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 SBT were stretched to optimal length (Lo), and basal spontaneous activity at Lo 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 > or = 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SBT or in other groups compared to control tissue. After SBT, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SBT (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.
Shibata
C
C
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota, UK.
Balsiger
B M
BM
Anding
W J
WJ
Sarr
M G
MG
D000322:Adrenergic Agonists / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000502:physiology; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000502:physiology*; D007082:Ileum / Q000294:innervation*; D007421:Intestine, Small / Q000637:transplantation*; D007583:Jejunum / Q000294:innervation; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000503:physiopathology; D014185:Transplantation, Isogeneic
D000322:Adrenergic Agonists; D018679:Cholinergic Agonists; D018723:Bethanechol; D009638:Norepinephrine