- 期刊
Peptide YY and Neuropeptide Y Inhibit Substance P Induced Contraction in Guinea Pig Esophagus
勝肽YY及神經勝肽Y抑制P物質引起之食道收縮
摘要
過去的研究指出，膽囊收縮素及P物質(substance P)引起食道收縮，而勝肽YY(peptide YY, PYY)及神經勝肽Y(neuropeptide Y, NPY)抑制膽囊收縮素引起的食道收縮。對於勝肽YY或神經勝肽Y抑制P物質引起之食道收縮則仍未有報告。本計畫探討勝肽YY及神經勝肽Y抑制P物質引起的食道收縮。離體天竺鼠食道肌肉條片之收縮以等長轉換器則量並記錄。P物質引起的食道肌肉收縮可為河豚毒素及阿托品阻斷。NK1型受體選擇性作用劑[Sar^9, Met(O2)^11]P物質引起收縮的效力大於P物質，而NK1型受體的拮抗劑GR-82334與濃度正比地抑制了P物質引起之收縮。這些結果顯示P物質作用於神經的NK1型受體引起食道收縮。另一方面，勝肽YY及神經勝肽Y單獨並不引起收縮。但是兩者都與濃度正比而強力地抑制了P物質的收縮。勝肽YY相關勝肽抑制收縮的相對效力為勝肽YY大於神經勝肽Y，大於神經勝肽Y(13-36)而又大於［Leu^31, Pro^34］神經勝肽Y。這些結果顯示PYY/NPY Y2型受體的存在。本研究證實P物質主要作用於食道神經的NK1受體引起食道收縮，而勝肽YY及神經勝肽Y作用於Y2受體抑制了P物質引起的收縮。勝肽YY及神經勝肽Y對食道收縮有廣泛而強力的抑制作用，不僅抑制膽囊收縮素也抑制P物質引起的食道收縮。Y2型受體拮抗劑及NK1型受體作用劑可為逆流性食道炎的治療藥物。
並列摘要
Besides cholinergic and adrenergic nerves, many peptidergic nerves play important roles in esophageal function. Cholecystokinin (CCK) and substance P (SP) cause contraction of the esophagus. Peptide YY (PYY) and neuropeptide Y (NPY) inhibit CCK induced contraction. In this study, effects of PYY and NPY on SF induced esophageal contraction were investigated. Contraction of the guinea pig esophageal muscle strip was measured in vitro by an isometric transducer and recorded. SP induced tetrodotoxin and atropine-sensitive contraction. Both SP and [Sar^9, Met(O2)^11] SP, a tachykinin NK1 receptor selective agonist, concentration-dependently caused contraction. [Sar^9, Met(O2)^11] SP was more potent than SF. The NK1 receptor antagonist GR-82334 inhibited SP induced contraction. These indicate that SF induces contraction mainly through interaction with neural NK1 receptors. On the other hand, both PYY and NPY concentration-dependently inhibited contraction induced by SF. The relative potencies for PYY related peptides to inhibit SF induced contraction were PYY＞NPY＞NPY13-36＞[Leu^31, Pro^34] NPY＞ pancreatic polypeptide, indicating the existence of PYY/NPY Y2 receptors. We concluded that SP interacts with neural NK1 receptors to cause esophageal muscle contraction. PYY and NPY interact with Y2 receptors to inhibit this SP-induced muscle contraction. These findings demonstrate PYY and NPY have potent inhibitory action on SP induced esophageal contraction. Thus, PYY and NPY inhibit not only CCK but also SP induced contraction in the esophagus. Y2 receptor antagonists and NK1 receptor agonists are of potential therapeutic importance in gastroesophageal reflux disease.