Rattan S, Culver P J
Gastroenterology. 1987 Jul;93(1):121-8. doi: 10.1016/0016-5085(87)90323-4.
The objective of this study was to examine the influence of the commonly used antidiarrheal agent loperamide on the internal anal sphincter of anesthetized opossums. Loperamide caused a rise in internal anal sphincter pressures, and a decrease in the rectal distention-induced internal anal sphincter relaxation. To define the mechanism of decrease in the rectal distention response of the internal anal sphincter, we examined the effects of sacral efferent nerve stimulation, local intramural stimulation, and ganglionic stimulant (which acts at the postganglionic inhibitory neuron). Loperamide caused a significant decrease in the internal anal sphincter relaxation caused by sacral nerve stimulation, but not in that caused by local intramural stimulation and nicotine. These effects of loperamide on the internal anal sphincter were antagonized by naloxone. These findings suggest that the therapeutic effects of loperamide on the internal anal sphincter as an antidiarrheal agent are due to a rise in the tone of the sphincter and the inhibition of its relaxation in response to rectal distention. Both of these actions are mediated by activation of opioid receptors. The inhibition of internal anal sphincter relaxation induced by rectal distention (which mimicks recto-anal reflex) is due to inhibition of release of neurotransmitter from the preganglionic sacral nerve fibers.
本研究的目的是考察常用止泻药洛哌丁胺对麻醉负鼠肛门内括约肌的影响。洛哌丁胺可使肛门内括约肌压力升高，并使直肠扩张诱导的肛门内括约肌松弛减弱。为了明确肛门内括约肌对直肠扩张反应减弱的机制，我们考察了骶传出神经刺激、局部壁内刺激和神经节兴奋剂（作用于节后抑制性神经元）的效应。洛哌丁胺可使骶神经刺激引起的肛门内括约肌松弛显著减弱，但对局部壁内刺激和尼古丁引起的松弛无此作用。洛哌丁胺对肛门内括约肌的这些作用可被纳洛酮拮抗。这些发现提示，洛哌丁胺作为止泻药对肛门内括约肌的治疗作用是由于括约肌张力升高以及抑制其对直肠扩张的松弛反应。这两种作用均由阿片受体激活介导。直肠扩张（模拟直肠-肛门反射）诱导的肛门内括约肌松弛受抑制是由于节前骶神经纤维神经递质释放受抑制。
