Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
Am J Physiol Gastrointest Liver Physiol. 2012 Apr;302(7):G732-9. doi: 10.1152/ajpgi.00404.2011. Epub 2012 Jan 19.
We set out to determine the effect of peptide YY(3-36) (PYY(3-36)) on the gastric muscle tone in conscious rats by measuring intragastric pressure (IGP) during intragastric nutrient drink infusion. After an overnight fast, a chronically implanted gastric fistula was connected to a custom-made nutrient drink infusion system and a catheter to measure IGP. IGP was measured before and during the infusion of a nutrient drink (Nutridrink; 0.5 ml/min) until 10 ml was infused. Rats were treated with PYY(3-36) (0, 33, and 100 pmol·kg(-1)·min(-1)) in combination with a subcutaneous injection of the Y(2) receptor antagonists JNJ31020028 (10 mg/kg) or BIIE0246 (2 mg/kg). Experiments were also performed after subdiaphragmatic vagotomy and after pretreatment with 3 ml of nutrient drink (to mimic a fed state). IGP was compared as the average IGP during nutrient infusion, represented as means ± SE and compared using ANOVA. PYY(3-36) dose dependently increased the IGP during nutrient infusion (4.7 ± 0.3, 5.7 ± 0.5 and 7.3 ± 0.7 mmHg; P < 0.01) while JNJ31020028 and BIIE0246 could block this increase [4.4 ± 0.5 (P < 0.001) and 4.8 ± 0.4 (P < 0.05) mmHg, respectively]. Also in vagotomized rats, PYY(3-36) was able to significantly increase the IGP during, an effect attenuated by JNJ31020028. BIIE0246 and JNJ31020028 were not able to decrease the IGP when no PYY(3-36) was administered. PYY(3-36) increased gastric tone through an Y(2) receptor-mediated mechanism that does not involve the vagus nerve. Y(2) receptor antagonists were not able to decrease gastric tone without exogenous administration of PYY(3-36), indicating that Y(2) receptors do not play a crucial role in the determination of gastric tone in physiological conditions.
我们通过测量胃内营养饮料输注期间的胃内压 (IGP)，来确定肽 YY(3-36) (PYY(3-36)) 对清醒大鼠胃平滑肌张力的影响。在隔夜禁食后，将慢性植入的胃造口管连接到定制的营养饮料输注系统和测量 IGP 的导管上。在输注营养饮料 (Nutridrink；0.5 ml/min) 之前和期间测量 IGP，直到输注 10 ml。用 PYY(3-36)(0、33 和 100 pmol·kg(-1)·min(-1)) 联合皮下注射 Y(2)受体拮抗剂 JNJ31020028(10 mg/kg)或 BIIE0246(2 mg/kg) 处理大鼠。还在膈下迷走神经切断后和预处理 3 ml 营养饮料 (模拟进食状态) 后进行实验。IGP 比较为营养输注期间的平均 IGP，以平均值 ± SE 表示，并使用 ANOVA 进行比较。PYY(3-36) 剂量依赖性地增加营养输注期间的 IGP(4.7 ± 0.3、5.7 ± 0.5 和 7.3 ± 0.7 mmHg；P < 0.01)，而 JNJ31020028 和 BIIE0246 可以阻断这种增加[4.4 ± 0.5( P < 0.001) 和 4.8 ± 0.4( P < 0.05) mmHg，分别]。在迷走神经切断大鼠中，PYY(3-36) 也能显著增加 IGP，而 JNJ31020028 则减弱了这一作用。当没有给予 PYY(3-36)时，BIIE0246 和 JNJ31020028 不能降低 IGP。PYY(3-36) 通过 Y(2)受体介导的机制增加胃张力，该机制不涉及迷走神经。在没有外源性给予 PYY(3-36)的情况下，Y(2)受体拮抗剂不能降低胃张力，这表明 Y(2)受体在生理条件下确定胃张力中不起关键作用。
