Siproudhis L, Bellissant E, Juguet F, Allain H, Bretagne J F, Gosselin M
Gastroenterology Unit, Hôpital Pontchaillou, Rennes, France.
Clin Pharmacol Ther. 1998 Oct;64(4):424-32. doi: 10.1016/S0009-9236(98)90073-X.
Somatostatin is localized in the intestinal and pelvic nerves of the anorectum and it seems to act as an important neurotransmitter. However, previous analyses of octreotide (a somatostatin analog) effects on anal function showed conflicting results. By use of a dynamic model in healthy subjects, with comparison to the myogenic effect of glucagon, the aim of our study was to further investigate the pharmacologic targets of octreotide.
This was a placebo-controlled, randomized, double-blinded crossover study performed in 12 healthy volunteers who received octreotide, glucagon, or placebo intravenously on separate days. During each sequence, several pressure steps in 3 different protocols of rectal isobaric distension were applied with an electronic barostat. Manometric responses of the anal canal, adaptative volumes, and perception scores of the rectum were recorded.
During both phasic and stepwise distensions, a significant drug effect was encountered at the anal level. Compared with placebo, octreotide significantly increased pressures at both upper and lower levels of the anal canal. In contrast, glucagon decreased pressures at the upper part of the anal canal. Octreotide significantly decreased rectal volumes to phasic distension, but glucagon did not induce any change on rectal adaptation. In addition, neither drug modified perception scores.
This study suggests that octreotide acts on reflex arcs and rectal myenteric neurons rather than on anal myogenic targets that respond to glucagon.
生长抑素定位于肛门直肠的肠神经和盆腔神经，似乎起着重要的神经递质作用。然而，先前关于奥曲肽（一种生长抑素类似物）对肛门功能影响的分析结果相互矛盾。通过在健康受试者中使用动态模型，并与胰高血糖素的肌源性作用进行比较，我们研究的目的是进一步探究奥曲肽的药理靶点。
这是一项安慰剂对照、随机、双盲交叉研究，在12名健康志愿者中进行，他们在不同日期分别接受静脉注射奥曲肽、胰高血糖素或安慰剂。在每个序列中，使用电子恒压器在3种不同的直肠等压扩张方案中施加几个压力步骤。记录肛管的测压反应、适应性容量和直肠的感知评分。
在阶段性和逐步扩张过程中，在肛管水平均遇到显著的药物效应。与安慰剂相比，奥曲肽显著增加了肛管上下水平的压力。相比之下，胰高血糖素降低了肛管上部的压力。奥曲肽显著降低了对阶段性扩张的直肠容量，但胰高血糖素对直肠适应性没有引起任何变化。此外，两种药物均未改变感知评分。
本研究表明，奥曲肽作用于反射弧和直肠肌间神经元，而非作用于对胰高血糖素产生反应的肛门肌源性靶点。
