Background
Chronic extrinsic denervation induced by small bowel transplantation (SBT) results
in adrenergic hypersensitivity in rat ileum. This study evaluated the role of neuronal
and/or muscular β1-, β2-, and β3-adrenoceptor (AR) mechanisms on contractility.
Methods
Ileal longitudinal muscle strips from Lewis rats (n = 6 rats per group, 8 strips per rat): naïve controls (NC), 4 months after sham operation
(SC) or after syngeneic orthotopic SBT were studied in vitro. Spontaneous contractile
activity and dose responses (10−8-10−4 mol) to isoprenaline (IP), a nonspecific β-AR agonist were studied with or without
selective antagonists (10−5 mol), for β1- (atenolol), β2- (ICI 118551), or β3- (SR 59230A) AR subtypes in the presence or absence of tetrodotoxin (TTX; 10−6 mol; nerve blocker).
Results
pEC50 (neg log of EC50, which is the concentration where 50% of inhibition was observed) of IP was 7.2 ±
0.2 (mean value ± SEM) in SBT vs 6.3 ± 0.1 in SC and 6.3 ± 0.2 in NC (both P < .05 vs SBT), reflecting adrenergic hypersensitivity. β1- and β2-AR blockade induced a TTX-sensitive right shift of the curve only in SBT and normalized
pEC50 values from 7.2 ± 0.2 to 6.4 ± 0.1 and 7.2 ± 0.2 to 6.6 ± 0.1, respectively (P < .05). β3-AR blockade shifted the curve independent of the presence of TTX to the right in
all groups (all P < .05).
Conclusions
In rat ileum, adrenergic inhibition of contractility was dependent on muscular β3-AR pathways, whereas posttransplant hypersensitivity was due to upregulated neuronal
β1- and β2-AR mechanisms that were inactive before SBT.
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Article info
Publication history
Published online: November 30, 2007
Accepted:
June 30,
2007
Footnotes
Supported by the Swiss National Science Foundation (BMB; Nr. 31-61583.00).
Published as an abstract in Gastroenterology 2003;124(4 Suppl 1):M1332.
Identification
Copyright
© 2008 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
