Ouyang A, Clain C J, Snape W J, Cohen S
J Clin Invest. 1982 Mar;69(3):507-15. doi: 10.1172/jci110476.
Although opioid peptides have been demonstrated immunohistochemically in the feline intestine, the action of these peptides is unknown. The aims of this study were: (a) to determine the distal ileal and ileocecal sphincter (ICS) responses to morphine sulfate (MS), methionine enkephalin (ME) and leucine enkephalin (LE); (b) to determine the mechanism by which exogenous opiates mediate these responses; (c) to determine the type of receptor involved in mediating these responses and (d) to ascertain whether endogenous opiate-mediated responses may be vagally induced. The ICS responded to all three opiate agonists with tonic and phasic contractions, the latter being associated with increased spike activity. The ED(max) for ICS pressure response was 1 mug/kg for ME, 5 mug/kg for LE, and 150 mug/kg for MS. The distal ileum responded with increased spike activity and phasic contractions. The ED(max) for the ileal motility index response was 1.0 x 10(-1) mug/kg for ME, 1 mug/kg for LE, and 150 mug/kg for MS. Thus, both sites demonstrated similar dose-response relationships, both responding to at least 100 times lower doses of enkephalins than MS. The ICS contraction preceded ileal contractions. The ileal and ICS response was not antagonized by atropine, hexamethonium, phentolamine, propranolol, cinanserin, or tetrodotoxin. Naloxone, 600 mug/kg, antagonized the response to the enkephalins while 10 mug/kg antagonized the response to MS. Higher doses of the specific-receptor agonist SKF 10047 and kappa-receptor agonist ketocyclazocine were required before a contractile response was elicited. Electrical stimulation of the cervical vagus induced ICS contraction and a fall in blood pressure. The ICS contractile response but not the blood pressure response was inhibited by naloxone 1 mg/kg. These data indicate: (a) tonic and phasic ICS contraction followed by ileal contraction may be mediated through delta-type opiate receptors located in the muscle membrane and (b) opiate-mediated ICS contraction may be induced during vagal stimulation.
尽管已通过免疫组织化学方法在猫肠道中证实了阿片肽的存在,但其作用尚不清楚。本研究的目的是:(a) 确定远端回肠和回盲括约肌(ICS)对硫酸吗啡(MS)、甲硫氨酸脑啡肽(ME)和亮氨酸脑啡肽(LE)的反应;(b) 确定外源性阿片类药物介导这些反应的机制;(c) 确定介导这些反应所涉及的受体类型;以及 (d) 确定内源性阿片类药物介导的反应是否可能由迷走神经诱导。ICS 对所有三种阿片类激动剂均有紧张性和阶段性收缩反应,后者与动作电位活动增加有关。ICS 压力反应的最大有效剂量(ED(max)):ME 为 1 μg/kg,LE 为 5 μg/kg,MS 为 150 μg/kg。远端回肠的反应是动作电位活动增加和阶段性收缩。回肠蠕动指数反应的 ED(max):ME 为 1.0×10⁻¹ μg/kg,LE 为 1 μg/kg,MS 为 150 μg/kg。因此,两个部位均表现出相似的剂量反应关系,对脑啡肽的反应剂量均比对 MS 的反应剂量低至少 100 倍。ICS 的收缩先于回肠收缩。回肠和 ICS 的反应不受阿托品、六甲铵、酚妥拉明、普萘洛尔、辛那色林或河豚毒素的拮抗。600 μg/kg 的纳洛酮可拮抗对脑啡肽的反应,而 10 μg/kg 的纳洛酮可拮抗对 MS 的反应。在引发收缩反应之前,需要更高剂量的特异性受体激动剂 SKF 10047 和 κ 受体激动剂酮环唑新。电刺激颈迷走神经可诱导 ICS 收缩和血压下降。1 mg/kg 的纳洛酮可抑制 ICS 的收缩反应,但不抑制血压反应。这些数据表明:(a) ICS 的紧张性和阶段性收缩随后是回肠收缩,可能是通过位于肌膜上的 δ 型阿片受体介导的;(b) 阿片类药物介导的 ICS 收缩可能在迷走神经刺激期间被诱导。