Orally administered soymorphins, soy-derived opioid peptides, suppress feeding and intestinal transit via gut μ₁-receptor coupled to 5-HT_1A, D₂, and GABA_Bsystems

Abstract

Kaneko K, Iwasaki M, Yoshikawa M, Ohinata K. Orally administered soymorphins, soy-derived opioid peptides, suppress feeding and intestinal transit via gut 1-receptor coupled to 5-HT1A, D2, and GABAB systems. Am J Physiol Gastrointest Liver Physiol 299: G799 -G805, 2010. First published July 8, 2010; doi:10.1152/ajpgi.00081.2010.-We previously reported that soymorphins, -opioid agonist peptides derived from soy ␤-conglycinin ␤-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 -or 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-HT1A, dopamine D2, or GABAB receptor, respectively. We then examined the order of activation of 5-HT1A, D2, and GABAB 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 D2 agonistinduced small intestinal transit suppression, was inhibited by saclofen, but not by WAY100135. Baclofen, a GABAB agonist-induced small intestinal transit suppression, was not blocked by WAY100135 or raclopride. These results suggest that 5-HT1A activation elicits D2 followed by GABAB activations in small intestinal motility. We conclude that orally administered soymorphins suppress food intake and small intestinal transit via 1-opioid receptor coupled to 5-HT1A, D2, and GABAB systems. anorexigenic activity; small intestinal motility; 1-opioid receptor; soy ␤-conglycinin ␤-subunit IT IS KNOWN THAT a number of bioactive peptides derived from enzymatic digest of food proteins exhibit various physiological actions, such as opioid (6,43,45), hypotensive (25, 49), cholesterol-lowering (41), anxiolytic (13, 30), and memoryenhancing (32, 42) activities. Among them, several peptides sometimes suppressed food intake after oral administration in rodents (14,24,27). We previously reported that hypotensive and vasorelaxing tripeptides, rapakinin (Arg-Ile-Tyr), derived from rapeseed, suppressed food intake via CCK release after oral administration in mice (24). Orally administered tetrapeptide ␤-lactotensin (His-Ile-Arg-Leu) was derived from bovine ␤-lactoglobulin through activation of CRF and CGRP receptors (14).It is generally known that opioid agonists stimulate food intake in animals (5). For example, -opioid agonists, including morphine or endomorphin-1 or -2, stimula...

Egg White Hydrolysate Can Be a Low-Allergenic Food Material to Suppress Ectopic Fat Accumulation in Rats Fed an Equicaloric Diet

“…We also considered that specific peptides derived from EW can suppress intestinal fat absorption as well as food intake or appetite. Several peptides derived from EW and other food materials suppressed food intake in rodents via several mechanisms (25,26). It has been suggested that stimulation of gastric hormone secretion by dietary proteins and their physicochemical properties influences gastric emptying time and intestinal absorption of several nutrients (12,27).…”

“…The meal transit rate in the small intestine can be associated with the food intake and fat absorption and is often used to evaluate the suppressive effects on food intake, appetite, and digestion (14,26). However, like the results of intestinal fat absorption, the meal transit was not suppressed by a single administration of the EW or EWH (Fig.…”

The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling

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