Rickenbacher Andreas, Seiler Roland, Honegger Ulrich, Shaw Sidney G, Balsiger Bruno M
Gastroenterology Unit (Inselspital), University of Bern, Switzerland.
Surgery. 2008 Jan;143(1):94-102. doi: 10.1016/j.surg.2007.06.034. Epub 2007 Dec 3.
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 beta1-, beta2-, and beta3-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 beta-AR agonist were studied with or without selective antagonists (10(-5) mol), for beta1- (atenolol), beta2- (ICI 118551), or beta3- (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. Beta1- and beta2-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). Beta3-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 beta3-AR pathways, whereas posttransplant hypersensitivity was due to upregulated neuronal beta1- and beta2-AR mechanisms that were inactive before SBT.
小肠移植（SBT）诱导的慢性外源性去神经支配导致大鼠回肠肾上腺素能超敏反应。本研究评估了神经元和/或肌肉β1 -、β2 -和β3 -肾上腺素能受体（AR）机制对收缩性的作用。
采用来自Lewis大鼠的回肠纵肌条（每组6只大鼠，每只大鼠8条肌条）：未处理的对照组（NC）、假手术（SC）或同基因原位SBT术后4个月的大鼠，进行体外研究。在有或没有选择性拮抗剂（10⁻⁵ mol）的情况下，研究对异丙肾上腺素（IP，一种非特异性β - AR激动剂）的自发收缩活性和剂量反应（10⁻⁸ - 10⁻⁴ mol），拮抗剂分别针对β1 -（阿替洛尔）、β2 -（ICI 118551）或β3 -（SR 59230A）AR亚型，同时设置有无河豚毒素（TTX；10⁻⁶ mol；神经阻滞剂）的情况。
SBT组中IP的pEC50（EC50的负对数，即观察到50%抑制的浓度）为7.2 ± 0.2（平均值 ± 标准误），而SC组为6.3 ± 0.1，NC组为6.3 ± 0.2（与SBT组相比，P均 < 0.05），反映了肾上腺素能超敏反应。β1 -和β2 - AR阻断仅在SBT组诱导了TTX敏感的曲线右移，pEC50值分别从7.2 ± 0.2恢复到6.4 ± 0.1和从7.2 ± 0.2恢复到6.6 ± 0.1（P < 0.05）。β3 - AR阻断使所有组的曲线在有无TTX的情况下均右移（所有P < 0.05）。
在大鼠回肠中，肾上腺素能对收缩性的抑制依赖于肌肉β3 - AR途径，而移植后超敏反应是由于神经元β1 -和β2 - AR机制上调，这些机制在SBT前是无活性的。
