Kromer W, Steigemann N, Shearman G T
Naunyn Schmiedebergs Arch Pharmacol. 1982 Dec;321(3):218-22. doi: 10.1007/BF00505489.
The purpose of this study was to investigate the differential involvement of distinct types of opioid receptors in the modulation of intestinal peristalsis compared to electrically induced longitudinal muscle contractions. Like naloxone, the proposed sigma-agonist and mu-antagonist SKF 10,047 (N-allyl-normetazocine) dose-dependently enhanced peristaltic circular muscle contractions in the isolated guinea-pig ileum. Pre-application of SKF 10,047 at a concentration which itself enhanced peristalsis by 20% on average strongly attenuated the inhibition of peristalsis produced by opioids previously proposed to act via mu-opioid-receptors in the guinea-pig ileum, i.e. normorphine, beta-endorphin, D-Ala2-D-Leu5-enkephalin and d-Ser2-L-Leu5-enkephalyl-Thr, but less strongly attenuated the inhibition produced by compounds suggested to act via kappa-opioid-receptors in this tissue, i.e. ethylketazocine and dynorphin (1-13). In contrast to its effect on peristalsis, SKF 10,047 inhibited the electrically induced contractions of the myenteric plexus-longitudinal muscle preparation in a naloxone-reversible fashion. It may be concluded that mu-and kappa-opioid receptors are of a greater functional significance than sigma-receptors in the control of peristalsis. sigma-Receptors might participate predominantly in modulating the release of acetylcholine which underlies the electrically induced longitudinal muscle contraction.
本研究的目的是调查与电诱导的纵肌收缩相比，不同类型阿片受体在调节肠道蠕动中的差异作用。与纳洛酮一样，拟 sigma 激动剂和 mu 拮抗剂 SKF 10,047（N -烯丙基 - 去甲美沙酮）在离体豚鼠回肠中剂量依赖性地增强蠕动性环肌收缩。以平均能使蠕动增强 20%的浓度预先应用 SKF 10,047，能强烈减弱先前提出的通过豚鼠回肠中的 mu 阿片受体起作用的阿片类药物对蠕动的抑制作用，即去甲吗啡、β -内啡肽、D -丙氨酸 2 - D -亮氨酸 5 -脑啡肽和 d -丝氨酸 2 - L -亮氨酸 5 -脑啡肽 -苏氨酸，但对该组织中通过 kappa 阿片受体起作用的化合物所产生的抑制作用减弱程度较小，即乙基酮唑辛和强啡肽（1 - 13）。与它对蠕动的作用相反，SKF 10,047 以纳洛酮可逆的方式抑制肠肌丛 -纵肌标本的电诱导收缩。可以得出结论，在蠕动控制中，mu 和 kappa 阿片受体比 sigma 受体具有更大的功能意义。sigma 受体可能主要参与调节乙酰胆碱的释放，而乙酰胆碱是电诱导纵肌收缩的基础。
