Abstracts
1999 Digestive Disease Week

# 2169 SMALL BOWEL TRANSPLANTATION INDUCES ADRENERGIC DENERVATION-HYPERSENSITIVITY IN ILEAL LONGITUDINAL SMOOTH MUSCLE IN RATS
N Ohtani, B M Balsiger, W J Anding, J A Duenes, Michael G Sarr, Mayo Clin, Rochester, MN

Previously, we showed that extrinsic denervation induced adrenergic hypersensitivity in circular smooth muscle of rat gut (Dig Dis Sci 1998). AIM: To determine effects of small bowel transplantation (SBT) on contractile properties of longitudinal smooth muscle of rat ileum. METHODS: Full thickness longitudinal muscle strips were harvested from three groups of Lewis rats (n=8 each): naive controls (NC), sham-operated controls (SC), and 8 wk after syngeneic (no rejection) orthotopic SBT (SBT8). Baseline spontaneous contractile activity (area under contractile curve) was evaluated in muscle strips stretched to optimal length in organ chambers. Dose-response to norepinephrine (NE, 3·10-8-10-5M) and bethanechol (Be, 3·10-8-3·10-6M) were obtained with and without tetrodotoxin (TTX, 10-6M) which blocks most nerve transmission within the muscle strip (neurally mediated events); the ED50 (negative log of concentration giving half maximal effect) was calculated. RESULTS(table): Baseline spontaneous activity did not change in SBT8 compared to NC. ED50 for NE was increased (lesser concentration for 50% response) in SBT8 (p<0.05). TTX had no effect on this response. ED50 for Be did not differ between groups (data not shown). SUMMARY: SBT induced an inhibitory adrenergic denervation-hypersensitivity in ileal longitudinal smooth muscle in rat. CONCLUSIONS: The adrenergic hypersensitivity of SBT appears to be mediated by changes at the level of the smooth muscle cell and not through changes in the enteric nervous system secondary to loss of extrinsic neural input (extrinsic denervation). These effects may explain some of the motor dysfunction after clinical SBT. Support: NIH DK39337 (MGS).

ED50**
Group	Baseline activity†	NE alone	NE with TTX
NC	8.4±1.0	6.2±0.2	6.4±0.1
SC	7.5±1.1	6.3±0.2	6.2±0.2
SBT8	7.1±0.6	6.9±0.1*	6.8±0.2*
Values=mean±SEM; n=8; †g·5 min/mg tissue; **negative log of drug concentrations; *p<0.05 compared to NC

Copyright 1996 - 1999, SSAT, Inc.