Poitras P, Miller P, Dickner M, Mao Y K, Daniel E E, St-Pierre S, Trudel L
Centre de recherche clinique André-Viallet, Hôpital Saint-Luc, Université de Montréal, Québec, Canada.
Peptides. 1996;17(4):701-7. doi: 10.1016/0196-9781(96)00053-8.
Motilin, a 22-amino acid peptide synthesized in endocrine cells of intestinal mucosa, stimulates GI smooth muscle contractility. To elucidate the mode of action of motilin, we attempted to determine whether motilin receptors are localized on nerve cells or on smooth muscle cells of the GI tract. Mucosa-free tissues from rabbit antrum and duodenum were homogenized separately with a Polytron prior to differential centrifugation to obtain synaptosome or plasma membrane-enriched fractions, as determined by the distribution of [3H]saxitoxin (SAX) binding (neural membranes) and 5' nucleotidase (5'N) activity (smooth muscle plasma membranes). Motilin binding was evaluated by the displacement of [125I]motilin by motilin (1-22) on the various membrane fractions. In the antrum, motilin binding was highly correlated with SAX binding (r = 0.81, p < 0.0005), and also significantly with 5'N activity (r = 0.54, p < 0.05). In the duodenum, motilin binding correlated significantly with 5'N activity (r = 0.67, p < 0.005), but not with SAX binding (r = -0.11, NS). Receptor affinity, for the motilin antagonist MOT(1-12)[CH2NH]10-11, for motilin(1-22), and for the motilin agonist erythromycin lactobionate was significantly (p < 0.001, p < 0.001, and p < 0.05, respectively) higher in SAX-enriched fractions from the antrum than in 5'N-enriched fractions from the duodenum. Therefore, in the rabbit: 1) motilin receptors appear to be predominantly located on nerve tissues in the antrum and restricted to smooth muscle cells in the duodenum, and 2) antral receptors and duodenal receptors displayed different pharmacological characteristics, probably corresponding to two specific and heterogeneous motilin receptor subtypes.
胃动素是一种由肠黏膜内分泌细胞合成的含22个氨基酸的肽，可刺激胃肠道平滑肌收缩。为阐明胃动素的作用方式，我们试图确定胃动素受体是位于胃肠道的神经细胞还是平滑肌细胞上。兔胃窦和十二指肠的无黏膜组织在进行差速离心之前，先用Polytron分别匀浆，以获得富含突触体或质膜的组分，这是通过[3H]石房蛤毒素（SAX）结合（神经膜）和5'核苷酸酶（5'N）活性（平滑肌质膜）的分布来确定的。通过胃动素（1-22）对各种膜组分上[125I]胃动素的置换来评估胃动素结合情况。在胃窦中，胃动素结合与SAX结合高度相关（r = 0.81，p < 0.0005），与5'N活性也显著相关（r = 0.54，p < 0.05）。在十二指肠中，胃动素结合与5'N活性显著相关（r = 0.67，p < 0.005），但与SAX结合无关（r = -0.11，无显著性差异）。胃动素拮抗剂MOT(1-12)[CH2NH]10-11、胃动素(1-22)和胃动素激动剂乳糖酸红霉素的受体亲和力，在来自胃窦的富含SAX的组分中分别显著高于来自十二指肠的富含5'N的组分（分别为p < 0.001、p < 0.001和p < 0.05）。因此，在兔中：1）胃动素受体似乎主要位于胃窦的神经组织上，而局限于十二指肠的平滑肌细胞上；2）胃窦受体和十二指肠受体表现出不同的药理学特性，可能对应于两种特定的、异质性的胃动素受体亚型。
