Orally administered soymorphins, soy-derived opioid peptides, suppress feeding and intestinal transit via gut [[mu].sub.1]-receptor coupled to [5-HT.sub.1A], [D.sub.2], and [GABA.sub.B] systems

We previously reported that soymorphins, [mu]-opioid agonist peptides derived from soy [beta]-conglycinin [beta]-subunit, have anxiolytic-like activity. The aim of this study was to investigate the effects of soymorphins on food intake and gut motility, along with their mechanism. We found that soymorphins decreases food intake after oral administration in fasted mice. Orally administered soymorphins suppressed small intestinal transit at lower dose than that of anorexigenic activity. Suppression of food intake and small intestinal transit after oral administration of soymorphins was inhibited by naloxone or naloxonazine, antagonists of [mu]- or [[mu].sub.1]-opioid receptor, respectively, after oral but not intraperitoneal administration. The inhibitory activities of small intestinal transit by soymorphins were also inhibited by WAY100135, raclopride, or saclofen, antagonists for serotonin 5-HTIA, dopamine 02, or GABAB receptor, respectively. We then examined the order of activation of 5-[HT.sub.1A], [D.sub.2], and [GABA.sub.B] receptors, using their agonists and antagonists. The inhibitory effect of 8-hydroxy-2-dipropylaminotetralin hydrobromide, a 5-HT1A agonist, after oral administration on small intestinal transit was blocked by raclopride or saclofen. Bromocriptine, a [D.sub.2] agonistinduced small intestinal transit suppression, was inhibited by saclofen, but not by WAY100135. Baclofen, a [GABA.sub.B] agonist-induced small intestinal transit suppression, was not blocked by WAY100135 or raclopride. These results suggest that 5-[HT.sub.1A] activation elicits [D.sub.2] followed by GABAB activations in small intestinal motility. We conclude that orally administered soymorphins suppress food intake and small intestinal transit via [[mu].sub.1]-opioid receptor coupled to 5-[HT.sub.1A], [D.sub.2], and [GABA.sub.B] systems. anorexigenic activity; small intestinal motility; [[mu].sub.1]-opioid receptor; soy [beta]-conglycinin [beta]-subunit doi: 10.1152/ajpgi.00081.2010.