Rubiscolin‑6 rapidly suppresses the postprandial motility of the gastric antrum and subsequently increases food intake via δ‑opioid receptors in mice

Ataka,Koji; Asakawa,Akihiro; Kato,Ikuo

doi:10.3892/mmr.2022.12856

Rubiscolin‑6 rapidly suppresses the postprandial motility of the gastric antrum and subsequently increases food intake via δ‑opioid receptors in mice

Authors:
- Koji Ataka
- Akihiro Asakawa
- Ikuo Kato
View Affiliations

Affiliations: Laboratory of Medical Biochemistry, Kobe Pharmaceutical University, Kobe 658‑8558, Japan, Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8544, Japan
Published online on: September 15, 2022 https://doi.org/10.3892/mmr.2022.12856
Article Number: 340
Copyright: © Ataka et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Rubiscolin‑6 is a food‑derived opioid peptide found in Spinacia oleracea that has anti‑nociceptive, memory‑enhancing, anxiolytic‑like and anti‑depressant effects. Rubiscolin‑6 has been reported to have two opposing effects on food intake. Food intake is closely connected to gut motility; however, to the best of our knowledge, the effect of rubiscolin‑6 on gut motility has not been reported. The present study aimed to investigate the effect of rubiscolin‑6 on postprandial motility of the gastric antrum in conscious mice. A catheter was implanted in the gastric antrum of male C57BL/6J mice. Manometric measurements were performed in fasted male mice and chow was then provided to assess motility in the fed state. Rubiscolin‑6, the δ‑opioid receptor antagonist naltrindole, a mixture of rubiscolin‑6 and naltrindole, or vehicle was administered intraperitoneally 30 min after eating. The percentage motor index (%MI) was then calculated. Cumulative food intake was measured in both ad libitum‑fed and overnight‑fasted mice. The %MI was significantly lower in mice treated with rubiscolin‑6 compared with that in the other groups, but normalized by treatment with the rubiscolin‑6/naltrindole mixture. The decrease in %MI induced by rubiscolin‑6 remained for 1 h after administration. Cumulative food intake was significantly higher 4 and 6 h after rubiscolin‑6 administration in ad libitum‑fed mice but was normalized by the rubiscolin‑6/naltrindole mixture. Food intake 30 min after rubiscolin‑6 administration was normal, but was higher in mice treated with the rubiscolin‑6/naltrindole mixture. Thus, rubiscolin‑6 may have a rapid effect to reduce postprandial antral motility and may subsequently increase food intake after this inhibitory effect disappears. These effects were revealed to be mediated through δ‑opioid receptors. The orexigenic effect of rubiscolin‑6 may be applicable to the treatment of anorexia and cachexia.

View Figures

View References

1	Chakrabarti S, Guha S and Majumder K: Food-derived bioactive peptides in human health: Challenges and opportunities. Nutrients. 10:17382018. View Article : Google Scholar : PubMed/NCBI
2	Tyagi A, Daliri EBM, Ofosu FK, Yeon SJ and Oh DH: Food-derived opioid peptides in human health: A review. Int J Mol Sci. 21:88252020. View Article : Google Scholar : PubMed/NCBI
3	Yang S, Yunden J, Sonoda S, Doyama N, Lipkowski AW, Kawamura Y and Yoshikawa M: Rubiscolin, a delta selective opioid peptide derived from plant Rubisco. FEBS Lett. 509:213–217. 2001. View Article : Google Scholar : PubMed/NCBI
4	Bar-On YM and Milo R: The global mass and average rate of rubisco. Proc Natl Acad Sci USA. 116:4738–4743. 2019. View Article : Google Scholar : PubMed/NCBI
5	Ellis RJ: The most abundant protein in the world. Trends Biochem Sci. 4:241–244. 1979. View Article : Google Scholar
6	Yang S, Kawamura Y and Yoshikawa M: Effect of rubiscolin, a opioid peptide derived from Rubisco, on memory consolidation. Peptides. 24:325–328. 2003. View Article : Google Scholar : PubMed/NCBI
7	Hirata H, Sonoda S, Agui S, Yoshida M, Ohinata K and Yoshikawa M: Rubiscolin-6, a delta opioid peptide derived from spinach Rubisco, has anxiolytic effect via activating sigma1 and dopamine D1 receptors. Peptides. 28:1998–2003. 2007. View Article : Google Scholar : PubMed/NCBI
8	Mitsumoto Y, Sato R, Tagawa N and Kato I: Rubiscolin-6, a δ-opioid peptide from spinach RuBisCO, exerts antidepressant-like effect in restraint-stressed mice. J Nutr Sci Vitaminol (Tokyo). 65:202–204. 2019. View Article : Google Scholar : PubMed/NCBI
9	Kaneko K, Lazarus M, Miyamoto C, Oishi Y, Nagata N, Yang S, Yoshikawa M, Aritake K, Furuyashiki T, Narumiya S, et al: Orally administered rubiscolin-6, a δ opioid peptide derived from Rubisco, stimulates food intake via leptomeningeal lipocallin-type prostaglandin D synthase in mice. Mol Nutr Food Res. 56:1315–1323. 2012. View Article : Google Scholar : PubMed/NCBI
10	Kaneko K, Mizushige T, Miyazaki Y, Lazarus M, Urade Y, Yoshikawa M, Kanamoto R and Ohinata K: δ-Opioid receptor activation stimulates normal diet intake but conversely suppresses high-fat diet intake in mice. Am J Physiol Regul Integr Comp Physiol. 306:R265–R272. 2014. View Article : Google Scholar : PubMed/NCBI
11	Gosnell BA, Levine AS and Morley JE: The stimulation of food intake by selective agonists of mu, kappa and delta opioid receptors. Life Sci. 38:1081–1088. 1986. View Article : Google Scholar : PubMed/NCBI
12	Sudakov SK, Nazarova GA and Alekseeva EV: Changes in feeding behavior, locomotor activity, and metabolism in rats upon modulation of opioid receptors in the gastrointestinal tract. Bull Exp Biol Med. 156:423–425. 2014. View Article : Google Scholar : PubMed/NCBI
13	Ruckebusch Y, Bardon T and Pairet M: Opioid control of the ruminant stomach motility: Functional importance of mu, kappa and delta receptors. Life Sci. 35:1731–1738. 1984. View Article : Google Scholar : PubMed/NCBI
14	Okamoto T, Kurahashi K and Fujiwara M: Effects of naloxone and opioid agonists on gastric excitatory responses to stimulation of the vagus nerve in cats. Br J Pharmacol. 95:329–334. 1988. View Article : Google Scholar : PubMed/NCBI
15	Ketwaroo GA, Cheng V and Lembo A: Opioid-induced bowel dysfunction. Curr Gastroenterol Rep. 15:3442013. View Article : Google Scholar : PubMed/NCBI
16	Camilleri M: Peripheral mechanisms in appetite regulation. Gastroenterology. 148:1219–1233. 2015. View Article : Google Scholar : PubMed/NCBI
17	Janssen P, Berghe PV, Verschueren S, Lehmann A, Depoortere I and Tack J: Review article: The role of gastric motility in the control of food intake. Aliment Pharmacol Ther. 33:880–894. 2011. View Article : Google Scholar : PubMed/NCBI
18	Sturm K, Parker B, Wishart J, Feinle-Bisset C, Jones KL, Chapman I and Horowitz M: Energy intake and appetite are related to antral area in healthy young and older subjects. Am J Clin Nutr. 80:656–667. 2004. View Article : Google Scholar : PubMed/NCBI
19	Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H and Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 402:656–660. 1999. View Article : Google Scholar : PubMed/NCBI
20	Fujino K, Inui A, Asakawa A, Kihara N, Fujimura M and Fujimiya M: Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats. J Physiol. 550:227–240. 2003. View Article : Google Scholar : PubMed/NCBI
21	Chen CY, Inui A, Asakawa A, Fujino K, Kato I, Chen CC, Ueno N and Fujimiya M: Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Gastroenterology. 129:8–25. 2005. View Article : Google Scholar : PubMed/NCBI
22	Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, Makino S, Fujimiya M, Niijima A, Fujino MA and Kasuga M: Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology. 120:337–345. 2001. View Article : Google Scholar : PubMed/NCBI
23	Kairupan TS, Cheng KC, Asakawa A, Amitani H, Yagi T, Ataka K, Rokot NT, Kapantow NH, Kato I and Inui A: Rubiscolin-6 activates opioid receptors to enhance glucose uptake in skeletal muscle. J Food Drug Anal. 27:266–274. 2019. View Article : Google Scholar : PubMed/NCBI
24	Tanaka R, Inui A, Asakawa A, Atsuchi K, Ataka K and Fujimiya M: New method of manometric measurement of gastroduodenal motility in conscious mice: Effects of ghrelin and Y2 depletion. Am J Physiol Gastrointest Liver Physiol. 297:G1028–G1234. 2009. View Article : Google Scholar : PubMed/NCBI
25	Kawai S, Takagi Y, Kaneko S and Kurosawa T: Effect of three types of mixed anesthetic agents alternate to ketamine in mice. Exp Anim. 60:481–487. 2011. View Article : Google Scholar : PubMed/NCBI
26	Blignaut CJ, Steenkamp G, Loock D, Emslie R and Zeiler GE: Immobilization, cardiopulmonary and blood gas effects of ketamine-butorphanol-medetomidine versus butorphanol-midazolam-medetomidine in free-ranging serval (Leptailurus serval). Vet Anaesth Analg. 48:707–715. 2021. View Article : Google Scholar : PubMed/NCBI
27	Eggers B, Tordiffe ASW, Lamberski N, Lawrenz A, Sliwa A, Wilson B and Meyer LCR: EVALUATION OF TWO DOSES OF BUTORPHANOL-MEDETOMIDINE-MIDAZOLAM FOR THE IMMOBILIZATION OF WILD VERSUS CAPTIVE BLACK-FOOTED CATS (FELIS NIGRIPES). J Zoo Wildl Med. 51:497–506. 2020. View Article : Google Scholar : PubMed/NCBI
28	Verstegen J and Petcho A: Medetomidine-butorphanol-midazolam for anaesthesia in dogs and its reversal by atipamezole. Vet Rec. 132:353–357. 1993. View Article : Google Scholar : PubMed/NCBI
29	Holzer P: Opioid receptors in the gastrointestinal tract. Regul Pept. 155:11–17. 2009. View Article : Google Scholar : PubMed/NCBI
30	Holle GE and Steinbach E: Different endogenous opioid effects on delta- and mu-receptor subtypes in antral and duodenal motility of conscious dogs. Dig Dis Sci. 47:1027–1033. 2002. View Article : Google Scholar : PubMed/NCBI
31	Porreca F, Mosberg HI, Hurst R, Hruby VJ and Burks TF: Roles of mu, delta and kappa opioid receptors in spinal and supraspinal mediation of gastrointestinal transit effects and hot-plate analgesia in the mouse. J Pharmacol Exp Ther. 230:341–348. 1984.PubMed/NCBI
32	Galligan JJ, Mosberg HI, Hurst R, Hruby VJ and Burks TF: Cerebral delta opioid receptors mediate analgesia but not the intestinal motility effects of intracerebroventricularly administered opioids. J Pharmacol Exp Ther. 229:641–648. 1984.PubMed/NCBI
33	Poole DP, Pelayo JC, Scherrer G, Evans CJ, Kieffer BL and Bunnett NW: Localization and regulation of fluorescently labeled delta opioid receptor, expressed in enteric neurons of mice. Gastroenterology. 141:982–991. 2011. View Article : Google Scholar : PubMed/NCBI
34	Wittert G, Hope P and Pyle D: Tissue distribution of opioid receptor gene expression in the rat. Biochem Biophys Res Commun. 218:877–881. 1996. View Article : Google Scholar : PubMed/NCBI
35	Schwartz MW, Woods SC, Porte D Jr, Seeley RJ and Baskin DG: Central nervous system control of food intake. Nature. 404:661–671. 2000. View Article : Google Scholar : PubMed/NCBI
36	Israel Y, Kandov Y, Khaimova E, Kest A, Lewis SR, Pasternak GW, Pan YX, Rossi GC and Bodnar RJ: NPY-induced feeding: Pharmacological characterization using selective opioid antagonists and antisense probes in rats. Peptides. 26:1167–1175. 2005. View Article : Google Scholar : PubMed/NCBI
37	Mercer RE, Chee MJ and Colmers WF: The role of NPY in hypothalamic mediated food intake. Front Neuroendocrinol. 32:398–415. 2011. View Article : Google Scholar : PubMed/NCBI