Wiley J W, Lu Y X, Chung O Y
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Gastroenterology. 1991 Apr;100(4):865-72. doi: 10.1016/0016-5085(91)90257-l.
The pathway by which peptide YY inhibits upper gastrointestinal motility is largely unknown and prompted this investigation. Muscle tension and [3H]acetylcholine release studies were performed on isolated muscle strips and slices obtained from the guinea pig stomach. Peptide YY [0.1-1000 nmol/L; concentration of half-maximal effect (EC50), 6 nmol/L] caused concentration-dependent relaxation of longitudinally oriented muscle strips that was unaffected by hexamethonium but was blocked by atropine and tetrodotoxin, suggesting that the peptide inhibited postganglionic cholinergic neurotransmission. In addition, peptide YY (1 mumol/L) reduced by 42% +/- 6% electrically stimulated muscle contractions that were blocked by atropine and tetrodotoxin, providing additional evidence that the peptide inhibits release of acetylcholine. Next, the effect of peptide YY on potassium-evoked release of [3H]acetylcholine and whether the peptide inhibits cyclic adenosine monophosphate-dependent release of acetylcholine were examined. Peptide YY (1 mumol/L) inhibited KCl (35 mmol/L)-evoked release of [3H]acetylcholine by 58% +/- 6%. The inhibitory action of peptide YY was unaffected by antagonists for dopamine-2, alpha-2, and opiate receptors that are known to mediate presynaptic inhibition. In addition, peptide YY reduced half-maximal forskolin and cholera toxin-evoked release of acetylcholine by 45% +/- 6% and 42% +/- 8%, respectively, suggesting that the peptide can inhibit cyclic adenosine monophosphate-dependent release of acetylcholine. This effect of peptide YY was reversed by pertussis toxin which prevents activation of the inhibitory guanine nucleotide binding protein coupled to adenylate cyclase. In summary, peptide YY inhibited basal and stimulated cholinergic neurotransmission in the guinea pig stomach. In addition, peptide YY antagonized cyclic adenosine monophosphate-mediated release of acetylcholine through a pertussis toxin-sensitive mechanism.
肽YY抑制上消化道动力的途径在很大程度上尚不清楚，这促使了本研究。对从豚鼠胃中获取的离体肌条和切片进行了肌张力和[³H]乙酰胆碱释放研究。肽YY[0.1 - 1000 nmol/L；半数最大效应浓度（EC50），6 nmol/L]引起纵向肌条浓度依赖性松弛，六甲铵对此无影响，但阿托品和河豚毒素可阻断该作用，提示该肽抑制节后胆碱能神经传递。此外，肽YY（1 μmol/L）使电刺激的肌肉收缩减少42%±6%，阿托品和河豚毒素可阻断该作用，这进一步证明该肽抑制乙酰胆碱释放。接下来，研究了肽YY对钾诱发的[³H]乙酰胆碱释放的影响以及该肽是否抑制环磷酸腺苷依赖性乙酰胆碱释放。肽YY（1 μmol/L）使氯化钾（35 mmol/L）诱发的[³H]乙酰胆碱释放减少58%±6%。肽YY的抑制作用不受已知介导突触前抑制的多巴胺 - 2、α - 2和阿片受体拮抗剂的影响。此外，肽YY分别使半数最大福斯高林和霍乱毒素诱发的乙酰胆碱释放减少45%±6%和42%±8%，提示该肽可抑制环磷酸腺苷依赖性乙酰胆碱释放。百日咳毒素可逆转肽YY的这种作用，百日咳毒素可阻止与腺苷酸环化酶偶联的抑制性鸟嘌呤核苷酸结合蛋白的激活。总之，肽YY抑制豚鼠胃中的基础和刺激的胆碱能神经传递。此外，肽YY通过百日咳毒素敏感机制拮抗环磷酸腺苷介导的乙酰胆碱释放。
