Depoortere I, Peeters T L, Vantrappen G
Department of Medical Research, Katholieke Universiteit Leuven, Belgium.
Peptides. 1991 Jan-Feb;12(1):89-94. doi: 10.1016/0196-9781(91)90172-l.
Binding studies with iodinated motilin revealed that in the small intestine motilin receptor density decreased aborally, disappeared in the caecum but returned in the colon and rectum. The highest density was in the distal colon (112 +/-/11 fmol/mg protein). The dissociation constant was the same in all regions (overall mean 1.10 +/- 0.22 nM). The ability of erythromycin-A (EM-A) and of two derivatives, EM-A N-oxide and EM-523, to displace motilin showed no difference between the tissues studied. Their order of potency was: motilin greater than EM-523 greater than EM-A greater than EM-A N-oxide. Proximal circular colonic smooth muscle strips showed maximal contractile responses towards motilin, EM-523 and EM-A of, respectively, 80 +/- 3%, 78 +/- 4% and 84 +/- 2% relative to the maximum obtained with acetylcholine. In proximal longitudinal muscle only a response of +/- 20% was obtained. Similar responses were obtained in the distal colon. The order of potency to induce contractions as reflected in the pED50 values was: motilin (8.03 +/- 0.1) greater than EM-523 (7.55 +/- 0.03) greater than EM-A (5.84 +/- 0.04) in proximal circular colon. The responses were not blocked by TTX (10(-6) M) or atropine (10(-6) M), but were reduced by verapamil (10(-6)M). The abundance of motilin receptors in colonic smooth muscle, if applicable to other species, opens new perspectives for the therapeutic applications of macrolides with motilin agonist properties.
用碘化胃动素进行的结合研究显示，在小肠中胃动素受体密度向口侧降低，在盲肠中消失，但在结肠和直肠中又恢复。最高密度出现在远端结肠（112±11 fmol/mg蛋白质）。解离常数在所有区域相同（总体平均值为1.10±0.22 nM）。红霉素A（EM-A）及其两种衍生物EM-A N-氧化物和EM-523置换胃动素的能力在研究的组织之间没有差异。它们的效价顺序为：胃动素＞EM-523＞EM-A＞EM-A N-氧化物。近端环形结肠平滑肌条对胃动素、EM-523和EM-A的最大收缩反应分别为相对于乙酰胆碱所获最大值的80±3%、78±4%和84±2%。在近端纵行肌中仅获得了±20%的反应。在远端结肠也获得了类似反应。以pED50值反映的诱导收缩的效价顺序为：在近端环形结肠中，胃动素（8.03±0.1）＞EM-523（7.55±0.03）＞EM-A（5.84±0.04）。这些反应不受TTX（10⁻⁶ M）或阿托品（10⁻⁶ M）的阻断，但被维拉帕米（10⁻⁶ M）减弱。如果结肠平滑肌中胃动素受体的丰富程度适用于其他物种，那么具有胃动素激动剂特性的大环内酯类药物的治疗应用将开启新的前景。
