Ouyang A, Vos P, Cohen S
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104.
Am J Physiol. 1988 Feb;254(2 Pt 1):G224-31. doi: 10.1152/ajpgi.1988.254.2.G224.
The sites of action of several opiate agonists at the feline ileocecal sphincter (ICS) were studied. Dose-response curves for the relatively specific ligands for the mu-, kappa-, and sigma-receptors were determined using morphine (mu-receptors), dynorphin-(1-13) (kappa-receptors), and N-allylnormetazocine (sigma-receptors). Each agonist results in a contractile ICS response. The ICS responded stereospecifically to the levo-isomer of N-allylnormetazocine. Atropine (30 micrograms/kg) or naloxone (100 micrograms/kg) antagonized the ICS response to morphine and to (-)-N-allylnormetazocine. Higher doses of naloxone were required to inhibit the ICS response to dynorphin. Neither atropine nor tetrodotoxin inhibited the ICS response to dynorphin. The ICS response to dynorphin was enhanced after tetrodotoxin. Morphine tachyphylaxis inhibited the ICS response to (-)-N-allylnormetazocine and vice versa. The ICS response to morphine was unaffected by vagotomy but inhibited by trimethaphan camsylate. This study suggests that dynorphin (kappa-receptor) acts at a smooth muscle receptor to mediate contraction and a neural receptor to mediate relaxation, while (-)-N-allylnormetazocine acts at the ICS via a mu-receptor. mu-Receptor activation causes ICS contraction via a cholinergic pathway.
研究了几种阿片类激动剂在猫回盲括约肌（ICS）的作用位点。使用吗啡（μ受体）、强啡肽-（1-13）（κ受体）和N-烯丙基去甲左啡诺（σ受体）测定了μ、κ和σ受体相对特异性配体的剂量反应曲线。每种激动剂均导致ICS产生收缩反应。ICS对N-烯丙基去甲左啡诺的左旋异构体产生立体特异性反应。阿托品（30微克/千克）或纳洛酮（100微克/千克）可拮抗ICS对吗啡和（-）-N-烯丙基去甲左啡诺的反应。需要更高剂量的纳洛酮来抑制ICS对强啡肽的反应。阿托品和河豚毒素均不能抑制ICS对强啡肽的反应。河豚毒素处理后，ICS对强啡肽的反应增强。吗啡快速耐受性抑制ICS对（-）-N-烯丙基去甲左啡诺的反应，反之亦然。ICS对吗啡的反应不受迷走神经切断术的影响，但可被樟磺咪芬抑制。该研究表明，强啡肽（κ受体）作用于平滑肌受体介导收缩，作用于神经受体介导舒张，而（-）-N-烯丙基去甲左啡诺通过μ受体作用于ICS。μ受体激活通过胆碱能途径引起ICS收缩。
