Sanger G J
J Pharm Pharmacol. 1987 Jun;39(6):449-53. doi: 10.1111/j.2042-7158.1987.tb03418.x.
Cholinergically mediated contractions were evoked by electrical field stimulation (EFS) of guinea-pig distal ileum longitudinal muscle-myenteric plexus strips. Metoclopramide, 0.1-100 microM, dose-dependently increased the contractions, probably by increasing acetylcholine (ACh) release; contractions evoked by exogenous ACh in the presence of tetrodotoxin were not increased by metoclopramide. 5-Hydroxytryptamine (5-HT) 0.3-30 nM similarly increased the height of the EFS-evoked contractions, although the maximum increase was less than for metoclopramide; higher concentrations of 5-HT (3 and 30 microM) had no effects or caused inhibition. The compound, ICS 205-930, 0.001-1 microM, had no effect on the EFS-evoked contractions and caused inhibition at higher concentrations. Preincubation of the tissues with 5-HT, 0.3-30 nM, did not affect the increase in EFS-evoked contractions caused by metoclopramide, 1 or 100 microM, whereas 5-HT, 3 and 30 microM, prevented the response caused by metoclopramide 1 microM, but not 100 microM. ICS 205-930, 0.1 microM, had no effect on the increase in EFS-evoked contractions caused by metoclopramide 1 or 100 microM. The drug, at least in low concentrations, may therefore increase cholinergically mediated contractions of guinea-pig ileum by stimulating 5-HT-like receptors within the myenteric plexus, which differ from those antagonized by ICS 205-930.
通过电场刺激（EFS）豚鼠回肠远端纵行肌-肌间神经丛条带诱发胆碱能介导的收缩。甲氧氯普胺，0.1 - 100微摩尔，剂量依赖性地增加收缩，可能是通过增加乙酰胆碱（ACh）释放；在存在河豚毒素的情况下，外源性ACh诱发的收缩未被甲氧氯普胺增强。5-羟色胺（5-HT）0.3 - 30纳摩尔同样增加EFS诱发收缩的高度，尽管最大增加幅度小于甲氧氯普胺；更高浓度的5-HT（3和30微摩尔）无作用或引起抑制。化合物ICS 205-930，0.001 - 1微摩尔，对EFS诱发的收缩无作用，在更高浓度时引起抑制。用0.3 - 30纳摩尔的5-HT对组织进行预孵育，不影响1或100微摩尔甲氧氯普胺引起的EFS诱发收缩的增加，而3和30微摩尔的5-HT可阻止1微摩尔甲氧氯普胺引起的反应，但不能阻止100微摩尔甲氧氯普胺引起的反应。0.1微摩尔的ICS 205-930对1或100微摩尔甲氧氯普胺引起的EFS诱发收缩的增加无作用。因此，该药物至少在低浓度时，可能通过刺激肌间神经丛内的5-HT样受体增加豚鼠回肠胆碱能介导的收缩，这些受体不同于被ICS 205-930拮抗的受体。
