TY - JOUR
T1 - Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats
AU - Shibata, Chikashi
AU - Balsiger, Bruno M.
AU - Anding, William J.
AU - Sarr, Michael G.
N1 - Funding Information:
Manuscript received June 2, 1997; accepte d July 16, 1997. From the Departmen t of Surgery and Gastroente rology Research Unit, Mao Cylinic and Foundation, Rochester, Minnesota. Parts of this work were presented at Dige stive Disease Week at the Ame rican Gastroe nterological Association in Washington, DC, on May 13, 1997, and are published in Gastroenteolorgy 112:A1473, 1997 and G astroenteolorgy 112:A824, 1997. This work was supported by USPHS NIH DK3937,3 Corporation, and the Mao Foyundation. Reprints unaailvable .
PY - 1997
Y1 - 1997
N2 - 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 (L0), and basal spontaneous activity at L 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 ≤ 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.
AB - 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 (L0), and basal spontaneous activity at L 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 ≤ 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.
KW - Denervation hypersensitivity
KW - Ileal smooth muscle
KW - Motility
KW - Norepinephrine
KW - Small bowel transplantation
KW - Smooth muscle contractility
UR - http://www.scopus.com/inward/record.url?scp=0031436248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031436248&partnerID=8YFLogxK
U2 - 10.1023/A:1018850214119
DO - 10.1023/A:1018850214119
M3 - Article
C2 - 9398797
AN - SCOPUS:0031436248
SN - 0163-2116
VL - 42
SP - 2213
EP - 2221
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 11
ER -