Rubiscolin-6, a δ opioid peptide derived from spinach Rubisco, has anxiolytic effect via activating σ1 and dopamine D1 receptors

Hirata, Hajime; Sonoda, Soushi; Agui, Shun; Yoshida, Minoru; Ohinata, Kousaku; Yoshikawa, Masaaki

doi:10.1016/j.peptides.2007.07.024

Cited by 82 publications

(82 citation statements)

References 32 publications

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“…A number of opioid peptides have been identified from enzymatic digest of food proteins (6,13,30,42,43,45). ␤-Casomorphin, a -opioid peptide derived from bovine ␤-casein, has more potent opioid activity than that of soymorphin in a guinea pig ileum-contraction assay; however, ␤-casomorphin-5 did not suppress food intake and gut motility after oral administration under our experimental conditions.…”

Section: Discussionmentioning

confidence: 64%

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

Kikuchi

Iwasaki

Yoshikawa

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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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...

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Section: Discussionmentioning

confidence: 64%

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

Kikuchi

Iwasaki

Yoshikawa

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…113 iii (-)-NIH-11082 is a non-peptide DOR agonist with antinociceptive 165 and antidepressant activity 107 without seizures. iv Rubiscolin, a bioactive hexapeptide derived from spinach rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase), 166 improves learning (specifically memory consolidation) at doses less than antinociceptive doses 126 and has been reported to be anxiolytic 167 and orexigenic. 168 v SB-235863, a non-peptide selective DOR agonist based on the pirrolomorphinan framework, 169 displays antinociceptive 170 and antihyperalgesic 53 properties.…”

Section: Azd2327mentioning

confidence: 99%

Delta opioid agonists: a concise update on potential therapeutic applications

Peppin

Raffa

2015

J Clin Pharm Ther

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SUMMARYWhat is known and objective: The endogenous opioid system co-evolved with chemical defences, or at times symbiotic relationships, between plants and other autotrophs and heterotrophic predators -thus, it is not surprising that endogenous opioid ligands and exogenous mimetic ligands produce diverse physiological effects. Among the endogenous opioid peptides (endomorphins, enkephalins, dynorphins and nociception/orphanin FQ) derived from the precursors encoded by four genes (PNOC, PENK, PDYN and POMC) are the pentapeptides Met-enkephalin (Tyr-Gly-Gly-Phe-Met) and Leu-enkephalin (Tyr-Gly-Gly-PheLeu). The physiological effects of the enkephalins are mediated via 7-transmembrane G protein-coupled receptors, including delta opioid receptor (DOR). We present a concise update on the status of progress and opportunities of this approach. Methods: A literature search of the PUBMED database and a combination of keywords including delta opioid receptor, analgesia, mood and individual compounds identified therein, from industry and other source, and from www.clinicaltrials.com. Results and discussion: DOR agonist and antagonist ligands have been developed with ever increasing affinity and selectivity for DOR over other opioid receptor subtypes and studied for therapeutic utility, primarily for pain relief, but also for other clinical endpoints. What is new and conclusion: Selective DOR agonists have been designed with a large increase in therapeutic window for a variety of potential CNS applications including pain, depression, and learning and memory among others. WHAT IS KNOWN AND OBJECTIVE

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“…Anxiolytic-like behavior was measured using the elevated plusmaze (EPM) test, which was performed as described previously [12,[18][19][20][21]. Four arms (25 cm long Â 5 cm wide) were placed 50 cm above the ground.…”

Section: Elevated Plus-maze Testmentioning

confidence: 99%

Central PGE₂exhibits anxiolytic-like activity via EP₁and EP₄receptors in a manner dependent on serotonin 5-HT_1A, dopamine D₁and GABA_Areceptors

et al. 2011

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a b s t r a c tWe found that centrally administered prostaglandin (PG) E 2 exhibited anxiolytic-like activity in the elevated plus-maze and open field test in mice. Agonists selective for EP 1 and EP 4 receptors, among four receptor subtypes for PGE 2 , mimicked the anxiolytic-like activity of PGE 2 . The anxiolytic-like activity of PGE 2 was blocked by an EP 1 or EP 4 antagonist, as well as in EP 4 but not EP 1 knockout mice. Central activation of either EP 1 or EP 4 receptors resulted in anxiolytic-like activity. The PGE 2 -induced anxiolytic-like activity was inhibited by antagonists for serotonin 5-HT 1A , dopamine D 1 and GABA A receptors. Taken together, PGE 2 exhibits anxiolytic-like activity via EP 1 and EP 4 receptors, with downstream involvement of 5-HT 1A , D 1 and GABA A receptor systems.

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Rubiscolin-6, a δ opioid peptide derived from spinach Rubisco, has anxiolytic effect via activating σ1 and dopamine D1 receptors

Cited by 82 publications

References 32 publications

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

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

Delta opioid agonists: a concise update on potential therapeutic applications

Central PGE₂exhibits anxiolytic-like activity via EP₁and EP₄receptors in a manner dependent on serotonin 5-HT_1A, dopamine D₁and GABA_Areceptors

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Rubiscolin-6, a δ opioid peptide derived from spinach Rubisco, has anxiolytic effect via activating σ1 and dopamine D1 receptors

Cited by 82 publications

References 32 publications

Orally administered soymorphins, soy-derived opioid peptides, suppress feeding and intestinal transit via gut μ1-receptor coupled to 5-HT1A, D2, and GABABsystems

Orally administered soymorphins, soy-derived opioid peptides, suppress feeding and intestinal transit via gut μ1-receptor coupled to 5-HT1A, D2, and GABABsystems

Delta opioid agonists: a concise update on potential therapeutic applications

Central PGE2exhibits anxiolytic-like activity via EP1and EP4receptors in a manner dependent on serotonin 5-HT1A, dopamine D1and GABAAreceptors

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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

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

Central PGE₂exhibits anxiolytic-like activity via EP₁and EP₄receptors in a manner dependent on serotonin 5-HT_1A, dopamine D₁and GABA_Areceptors