Kawakubo K, Yang H, Taché Y
CURE: Digestive Diseases Research Center, Veterans Administration Greater Los Angeles Healthcare System, CA 90073, USA.
Brain Res. 2000 Jan 31;854(1-2):30-4. doi: 10.1016/s0006-8993(99)02293-3.
We previously reported that intracisternal (i.c.) injection of peptide YY (PYY) and low doses of thyrotropin-releasing hormone (TRH) or TRH analog, RX 77368, increased the resistance of the gastric mucosa to ethanol injury through vagal pathways in rats. The gastroprotective effect of i.c. injection of PYY/neuropeptide NPY (NPY) agonists with differential in vitro affinity to the Y receptor subtypes was examined in urethane-anesthetized rats. Intragastric administration of ethanol (45%, 5 ml/kg) results in mucosal lesions covering 23+/-2% of the gastric corpus in 1 h. PYY (500 ng, i.c.) significantly reduced ethanol-induced gastric lesions by 52%. [Pro34]PYY (PYY-preferring/Y1/Y5/Y4 subtypes) injected i.c. at 50, 100, 200 or 500 ng, reduced dose dependently gastric lesions to 15.4+/-2.2%, 11.4+/-3.1%, 8.6+/-2.9% and 5.4+/-2.2%, respectively. PYY3-36, (Y2/Y4 subtypes), [Leu31, Pro34]NPY (Y1/Y5), NPY (Y3/Y1/Y5/Y2) and pancreatic polypeptide (PP, Y4) injected i.c. at 500 ng did not influence significantly ethanol-induced gastric lesions. Combined i.c. injection of RX 77368 (1 ng) and Pro34PYY (25 ng), at sub-threshold doses given singly, reduced ethanol-induced gastric injury to 12.9+/-2.3% while RX 77368 (1 ng) plus PYY3-36 (500 ng) or [Leu31, Pro34]NPY (25 ng) had no effect. These findings indicate that i.c. PYY-induced gastric protection against 45% ethanol is mediated by a Y receptor subtype which bears similarity with the putative PYY-preferring receptor and distinct from the currently defined Y1/Y5; in addition, there is a synergistic interaction between activation of this PYY-preferring receptor and i.c. TRH to increase the resistance of the gastric mucosa to injury caused by 45% ethanol.
我们之前报道过，脑池内（i.c.）注射肽YY（PYY）以及低剂量的促甲状腺激素释放激素（TRH）或TRH类似物RX 77368，可通过迷走神经途径增强大鼠胃黏膜对乙醇损伤的抵抗力。在氨基甲酸乙酯麻醉的大鼠中，研究了脑池内注射对Y受体亚型具有不同体外亲和力的PYY/神经肽NPY（NPY）激动剂的胃保护作用。胃内给予乙醇（45%，5 ml/kg）会在1小时内导致胃体部黏膜损伤面积达23±2%。PYY（500 ng，脑池内注射）可使乙醇诱导的胃损伤显著减少52%。[Pro34]PYY（优先作用于PYY/Y1/Y5/Y4亚型）脑池内注射50、100、200或500 ng时，可使胃损伤剂量依赖性地分别降至15.4±2.2%、11.4±3.1%、8.6±2.9%和5.4±2.2%。PYY3-36（Y2/Y4亚型）、[Leu31, Pro34]NPY（Y1/Y5）、NPY（Y3/Y1/Y5/Y2）和胰多肽（PP，Y4）脑池内注射500 ng时，对乙醇诱导的胃损伤无显著影响。单独给予时低于阈值剂量的RX 77368（1 ng）和Pro34PYY（25 ng）联合脑池内注射，可使乙醇诱导 的胃损伤降至12.9±2.3%，而RX 77368（1 ng）加PYY3-36（500 ng）或[Leu31, Pro34]NPY（25 ng）则无作用。这些发现表明，脑池内注射PYY诱导的针对45%乙醇的胃保护作用是由一种Y受体亚型介导的，该亚型与推测的优先作用于PYY的受体相似，且不同于目前定义的Y1/Y5；此外，这种优先作用于PYY的受体激活与脑池内注射TRH之间存在协同相互作用，可增强胃黏膜对45%乙醇所致损伤的抵抗力。
