|| Checking for direct PDF access through Ovid
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.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).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).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.